Biomarcadores na Doença de Alzheimer - neurosong.org · Doença de Alzheimer Norberto Anizio...
Transcript of Biomarcadores na Doença de Alzheimer - neurosong.org · Doença de Alzheimer Norberto Anizio...
Biomarcadores na Doenccedila de Alzheimer
Norberto Anizio Ferreira Frota
Prof Curso de Medicina da UNIFOR
Coordenador da Residecircncia em Neurologia do HGF
Secretaacuterio de Neurologia da ABNPG
Roteiro
bull Conceito
bull Evoluccedilatildeo Histoacuterica
bull Criteacuterios Diagnoacutesticos
bull RM
bull PET
bull Liquor
bull Aplicabilidade cliacutenica
O QUE Eacute UM BIOMARCADOR
bull Os biomarcadores podem ser definidos como umamedida objetiva e especiacutefica de um processo bioloacutegicoou patogecircnico podendo ser usados para avaliar o riscoou o prognoacutesticos da doenccedila guiar o diagnoacutesticocliacutenico ou monitorar intervenccedilotildees terapecircuticas
bull O biomarcador ideal deve detectar precocemente ecom grande precisatildeo uma caracteriacutesitca patoloacutegica dadoenccedila
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
Biomarcadores na praacutetica cliacutenica
bull Glicemia
bull FAN
bull Reaccedilatildeo de Wasserman ndash Siacutefilis
Detectar in vivo as alteraccedilotildees patoloacutegicas
Caso Cliacutenico
bull Ident MLR 59 anos economista
bull QP rdquoMovimentos Repetitivosrdquo
bull HDA Haacute dois anos movimentos repetitivos em matildeos
bull Deixou de dirigir ndash natildeo sabia tempo para passar marcha
bull Dificuldade em usar smartphone
Caso Cliacutenico
bull HPP cesariana depressatildeo
bull Med Desvenlafaxina 50mg Zolpiden 10mg
bull Haacutebitos etilismo leve
bull Alergia ndn
bull Hist Familiar Matildee com quadro demencial aos 62 anos
Avaliaccedilatildeo Cognitivabull ACE76100
atenccedilatildeo OT5 OE5 MI3 AC93-x-x-72-x=1518Memoacuteria1+6+4+6+5=2226FP peru pato pinto passaro preacutedio parque pneu=7FA galinha peru pato baleia cachorro gato peixe camaratildeo rato tartaruga passaros cavalo leatildeo=13(3+4=714)LIng1+3+1+2+1+1+10+2+1=2226V-E0+0+4+3+3=1016
Exame Neuroloacutegico
bull Equiliacutebrio movimentos em matildeo D e flexatildeoFM elevaccedilatildeo de MSD (levitaccedilatildeo e fica fazendo movimentos em MID)Reflexos Vivos
bull Apraxia evidente pior a DCoordenaccedilatildeo index nariz normal e leve disdiadococinesiaSensib Discreta anartestesia em MIDNC sem alteraccedilotildees
Hipoacutetese Diagnoacutestica
bull Degeneraccedilatildeo Cortico-Basal
bull Doenccedila de Alzheimer atiacutepica
E agora
Exames Complementares nas Demecircncias
bull Descartar causas secundaacuterias
bull Padrotildees especiacuteficos de atrofia
Nova Visatildeo
bull Diferenciaccedilatildeo dos tipos de demecircncia
bull Diagnoacutestico precoce
bull Marcador de evoluccedilatildeo
bull Resposta terapecircutica
Ressonacircncia Magneacuteticabull Natildeo deve ser mais utilizado como somente para
excluir causas secundaacuterias
bull Eacute um biomarcador de dano neuronal
bull Avaliar com cuidado atrofias assimeacutetricas
The n ew en g l an d j o u r n a l of med i c i n e
n engl j med 36423 nejmor g june 9 20112230
A Swedish study showed that subjects with mild
cognitive impairment who had low levels of
β-amyloid peptide 42 (Aβ42) and elevated levels
of tau protein in cerebrospinal f luid were sig-
nif icantly more likely to undergo progression to
Alzheimerrsquos disease than subjects without this
prof ile (hazard ratio 177 95 conf idence inter-
val 53 to 589) a similar relative risk of progres-
sion was associated with a low ratio of Aβ42 to
tau in the cerebrospinal f luid28 An international
multicenter study of 750 subjects with mild cogni-
tive impairment corroborated these general f ind-
ings2930 but used different cutoff points for ab-
normal f indings The reliability of these markers
is highly variable across laboratories standard-
ization will be needed before they are considered
for incorporation into routine care
The use of molecular imaging particularly of
amyloid plaques in the brain (Fig 3) has also been
studied as a possible approach to risk stratif ica-
tion31-33 In several studies subjects with mild cog-
nitive impairment in whom amyloid was detected
on positron-emission tomography (PET) with the
use of the amyloid-binding carbon 11ndashlabeled Pitts-
burgh compound B had more rapid progression to
Alzheimerrsquos disease than did subjects in whom
amyloid was not detected34 The rationale for using
this technique to predict disease progression is that
the presence of amyloid in a patient with mild
cognitive impairment is likely to indicate that the
patient has early Alzheimerrsquos disease however
amyloid has been detected on autopsy in clinical-
ly normal persons indicating that the predictive
value of this measure requires further study35
Management
From a clinical perspective patients with mild cog-
nitive impairment should not be labeled as having
early Alzheimerrsquos disease prodromal Alzheimerrsquos
disease or mild cognitive impairment of the Alz-
heimerrsquos disease type since the patient and fam-
ily are likely to hear only ―Alzheimerrsquos disease and
not appreciate the uncertainty of the association
with Alzheimerrsquos disease36 Clinicians should make
it clear that mild cognitive impairment is an abnor-
mal condition but that the precise outcome is not
certain
At present no medication intended for the
treatment of mild cognitive impairment has been
approved by the Food and Drug Administration
(FDA) In several placebo-controlled clinical trials
there was no signif icant reduction in rates of
progression to dementia among patients with
mild cognitive impairment who were treated with
agents used to treat Alzheimerrsquos disease (donepe-
zil galantamine and rivastigmine administered
at standard doses for Alzheimerrsquos disease for 2 to
4 years)537-40 In one trial evaluating the effects of
high-dose vitamin E (2000 IU daily) or donepezil
in persons with mild cognitive impairment do-
nep ezil signif icantly reduced the risk of pro-
gression to Alzheimerrsquos disease for the f irst 12
months of the study (and for up to 24 months in
the subgroup of subjects who were carriers of
APOE ε4) but had no signif icant effect on the
risk of Alz heimerrsquos disease at 36 months which
was the primary study outcome vitamin E did
not signif icantly reduce the risk of progression
at any time point assessed5
A B C
Figure 2 Coronal MRI Scans from Patients with Normal Cognition Mild Cognitive Impairment and Alzheimerrsquos
Disease
The arrows depict the hippocampal formations and the progressive atrophy characterizing the progression from nor-
mal cognition (Panel A) to mild cognitive impairment (Panel B) to Alzheimerrsquos disease (Panel C)
The New England Journal of Medicine
Downloaded from nejmorg at UECE on July 24 2016 For personal use only No other uses without permission
Copyright copy 2011 Massachusetts Medical Society All rights reserved
cl i n i cal pr act i ce
n engl j med 36423 nejmor g june 9 2011 2231
One potential explanation for the apparent lack
of eff icacy in the clinical trials of interventions in
persons with mild cognitive impairment mdash other
than a true absence of drug eff icacy mdash concerns
the heterogeneity of the subjects As the diagnos-
tic threshold moves to an earlier point in the clini-
cal spectrum of cognitive impairment the subtle
changes in cognition could be due to a variety of
causes other than a degenerative brain disease
making it diff icult to determine whether an inter-
vention has had a signif icant effect
There is some evidence of a potential benefit
from cognitive rehabilitation including the use of
mnemonics association strategies and computer-
assisted training programs4142 A recent systematic
review of the literature on cognitive rehabilitation
programs for persons with mild cognitive impair-
ment including some data from randomized clin-
ical trials showed signif icant improvement in
cognitive function at the end of training42
Observational data have shown associations
between the presence of cardiovascular risk factors
in patients with mild cognitive impairment and an
increased risk of progression to dementia7 Such
risk factors should be addressed although there
is no definitive evidence that modif ication of risk
factors slows disease progression In a randomized
trial that used the Cognitive Subscale of the Alz-
heimerrsquos Disease Assessment Scale to compare the
effect of a physical exercise program (brisk walking
for 150 minutes per week) with that of usual care
and education in persons with subjective memory
loss the exercise group had better cognitive func-
tion at 6 months (the primary study outcome) with
some residual benefit noted at 18 months43
Ar eas o f Un cer t ai n t y
More data are needed regarding the usefulness of
various potential predictors of progression to de-
mentia and their role in clinical practice Further
data on these concerns are awaited from the Alz-
heimerrsquos Disease Neuroimaging Initiative under
way in the United States and Canada2744 and from
similar ongoing studies in Japan Europe and Aus-
tralia Some of the goals of these studies are to
better understand the role of MRI f indings (eg
hippocampal atrophy)2245 f indings on 18FDG-PET
(patterns of hypometabolism in the brain) cere-
brospinal f luid markers (levels of Aβ42 and tau)
and f indings on molecular imaging (amyloid
plaques in the brain) in identifying the subgroup
of persons with amnestic mild cognitive impair-
ment who are likely to undergo progression to
clinical Alz hei merrsquos disease274647 Major challeng-
es are to determine optimal cutoff points for these
tests and to compare their relative reliability (alone
and in combination) Randomized trials are need-
ed to assess the potential benefits of pharmaco-
logic and lifestyle interventions in persons with
mild cognitive impairment who are predicted to
be at high risk for rapid progression to Alzheimerrsquos
A B C
Figure 3 Axial Scans of the Brain Obtained with Positron-Emission Tomography and the Use of Amyloid-Binding
Carbon 11ndashLabeled Pittsburgh Compound B
The yellow and red areas indicate retention of the amyloid-binding tracer reflecting amyloid deposits The patient
with normal cognition (Panel A) has no tracer retention whereas the patient with amnestic mild cognitive impair-
ment has an intermediate amount of tracer retention (Panel B) and the patient with Alzheimerrsquos disease has promi-
nent tracer retention (Panel C)
The New England Journal of Medicine
Downloaded from nejmorg at UECE on July 24 2016 For personal use only No other uses without permission
Copyright copy 2011 Massachusetts Medical Society All rights reserved
Outros Marcadores
bull Liacutequor
bull Dosagem de TAU (decaacuteda de 90)
bull Dosagem de AB-42
bull Growdon 1999 (AB-42 e TAU na DA)
Mattsson N et al 2009 JAMA
bull 750 pacientes com Comprometimento Cognitivo Leve
bull Seguimento por 2 anos
bull 271 evoluiram para DA
bull 59 apresentaram outras demecircncias
bull Baixos niacuteveis de Aβ-42 e altos de Fosfo-Tau com maior
acuraacutecia para evoluccedilatildeo para DA
bull 74 pacientes com Doenccedila de Alzheimer x 142 com
Comprometimento Cognitivo Leve e 82 controles
bull Hipometabolismo
- Precuneos
- Ciacutengulo Posterior
- Coacutertex Temporo-parietal
- Coacutertex Frontal
Koivunen et al Neurology 2011
bull 29 pacientes acompanhados por 2 anos
bull Avaliaccedilatildeo de PET com PIB e RM (Atrofia de
hipocampo)
bull 1729 converteram
bull Maior depoacutesito de PIB Ciacutengulo Posterior frontal lateral
temporal e putamem com maior atrofia
bull Pouca modificaccedilao no PIB em 2 anos
bull Aumento da atrofia
Hipoacutetese da Evoluccedilatildeo Temporal
dos processos fisiopatoloacutegicos
Biomarcador e CCL
Criteacuterios para Pesquisa DA
Porque utilizar biomarcador empacientes com quadros cognitivos
bull O paciente vai piorar dos sintomas cognitivos
bull Existe um processo patoloacutegico jaacute conhecido
bull Existe dano neuronal Topografia
bull Falsos positivos o que fazer
Ressonacircncia Magneacutetica de Cracircnio
bull Atrofia hipocampal
bull Casos leves ou assintomaacuteticos
bull Avaliaccedilatildeo de espessura cortical (Walhovd K et al 2010)
bull DTI (Sexton C et al 2011)
Ressonacircncia Magneacutetica
Vantagens
bull Disponibilidade
bull Visualizaccedilatildeo de atrofia
bull Possibilidade de vaacuterias mediccedilotildees
Limitaccedilotildees
bull Teacutecnicas habituaispoucos sensiacuteveis paraquadros leves
bull Reflete somente o danoneuronal
bull Teacutecnicas especiaispouca disponibilidade
Caso
bull RM laudo normal
PET-FDG
Vantagens
bull Sensibilidade
bull Reflete dano neuronal
Limitaccedilotildees
bull Custo
bull Sem ponto de corte
bull Natildeo especiacutefico do dano patoloacutegico
Caso
bull PET-FDG hipometabolismo FTP esquerdo e leve a Direita frontal e parietal
bull O que esse laudo mostra
bull Que eu consegui examinar e topografar direito
PET Amiloide
bull Dificuldades Iniciais
bull Marcador a base de Fluor
PET Tau and Amyloid-β Burden in Mild Alzheimers Disease Divergent Relationshipwith Age Cognition and Cerebrospinal Fluid BiomarkersKoychev I1 Gunn RN23 Firouzian A2 Lawson J1 Zamboni G1 Ridha B4 Sahakian BJ5 Rowe JB6 Thomas A7 Rochester L7 Ffytche D8 Howard R9 Zetterberg H9101112 MacKay C1 Lovestone S1 Deep and Frequent Phenotyping study team
J Alzheimers Dis 2017 Aug 8
PET Marcador Amiloacuteide
Vantagens
bull Refletem o processo patoloacutegico
bull Conseguem detectar indiviacuteduos assintomaacuteticos em risco
bull Predizem piora cliacutenica
Limitaccedilotildees
bull Custo
bull Disponibilidade
bull Normalizaccedilatildeo de pontos de corte
Caso
bull PET-Amiloacuteide
241 Estudos
11341 Pacientes
7086 Pacientes
Entatildeo vamos coletar Liacutequor para todos
Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory ClinicPatients in a Prospective CohortHandels RL12 Joore MA23 Vos SJ1 Aalten P1 Ramakers IH1 Rikkert MO4 Scheltens P5 Jansen WJ1 Visser PJ15 van Berckel BM5 van Domburg P6 Smid M7 Hoff E8 Hoogmoed J910 Bouwman F5 Claassen J4 Leentjens AF1 Wolfs CA1 Severens JL11 Verhey FR1Author information
bull 200 DA
bull 16 DA prodromica
bull 69 DFT
bull 59 DCB
bull 16 PSP
bull 44 DCL
bull 22 ACP
bull 41 Demecircncia Semacircntica
bull 52 Afasias logopecircnicas
bull 11 Afasias natildeo fluentes
bull 71 Depressatildeo
bull 49 Queixa subjetiva de memoacuteria
bull DA -100
bull DA prodromica-100
bull 439 dos outros pacientes tbpositivos
bull 818 ACP
bull 788 Afasia logopecircnica
bull 50 DCL
bull 458 DCB
bull 454 afasias natildeo fluentes
bull 366 demecircncia semacircnticas
bull 145 das DFT
bull 117 (Depressatildeo e QSM)
E o teste de Memoacuteria
bull Sensibilidade100
bull Especificidade de 748
bull Intrusotildees Sensibilidade de 83 e Especificidade72
bull 273 tinham deacuteficit hipocampal
bull 366 dos deprimidos
bull 40 DCL
bull 375 PSP
bull 319 DFT
bull 273 Afasia natildeo fluente
bull 227 ACP
bull 22 Demecircncia Semacircntica
bull 22 DCB
bull 58 Afasia logopecircnica
Existiu uma correlaccedilatildeo desempenho com os marcadores
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
Roteiro
bull Conceito
bull Evoluccedilatildeo Histoacuterica
bull Criteacuterios Diagnoacutesticos
bull RM
bull PET
bull Liquor
bull Aplicabilidade cliacutenica
O QUE Eacute UM BIOMARCADOR
bull Os biomarcadores podem ser definidos como umamedida objetiva e especiacutefica de um processo bioloacutegicoou patogecircnico podendo ser usados para avaliar o riscoou o prognoacutesticos da doenccedila guiar o diagnoacutesticocliacutenico ou monitorar intervenccedilotildees terapecircuticas
bull O biomarcador ideal deve detectar precocemente ecom grande precisatildeo uma caracteriacutesitca patoloacutegica dadoenccedila
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
Biomarcadores na praacutetica cliacutenica
bull Glicemia
bull FAN
bull Reaccedilatildeo de Wasserman ndash Siacutefilis
Detectar in vivo as alteraccedilotildees patoloacutegicas
Caso Cliacutenico
bull Ident MLR 59 anos economista
bull QP rdquoMovimentos Repetitivosrdquo
bull HDA Haacute dois anos movimentos repetitivos em matildeos
bull Deixou de dirigir ndash natildeo sabia tempo para passar marcha
bull Dificuldade em usar smartphone
Caso Cliacutenico
bull HPP cesariana depressatildeo
bull Med Desvenlafaxina 50mg Zolpiden 10mg
bull Haacutebitos etilismo leve
bull Alergia ndn
bull Hist Familiar Matildee com quadro demencial aos 62 anos
Avaliaccedilatildeo Cognitivabull ACE76100
atenccedilatildeo OT5 OE5 MI3 AC93-x-x-72-x=1518Memoacuteria1+6+4+6+5=2226FP peru pato pinto passaro preacutedio parque pneu=7FA galinha peru pato baleia cachorro gato peixe camaratildeo rato tartaruga passaros cavalo leatildeo=13(3+4=714)LIng1+3+1+2+1+1+10+2+1=2226V-E0+0+4+3+3=1016
Exame Neuroloacutegico
bull Equiliacutebrio movimentos em matildeo D e flexatildeoFM elevaccedilatildeo de MSD (levitaccedilatildeo e fica fazendo movimentos em MID)Reflexos Vivos
bull Apraxia evidente pior a DCoordenaccedilatildeo index nariz normal e leve disdiadococinesiaSensib Discreta anartestesia em MIDNC sem alteraccedilotildees
Hipoacutetese Diagnoacutestica
bull Degeneraccedilatildeo Cortico-Basal
bull Doenccedila de Alzheimer atiacutepica
E agora
Exames Complementares nas Demecircncias
bull Descartar causas secundaacuterias
bull Padrotildees especiacuteficos de atrofia
Nova Visatildeo
bull Diferenciaccedilatildeo dos tipos de demecircncia
bull Diagnoacutestico precoce
bull Marcador de evoluccedilatildeo
bull Resposta terapecircutica
Ressonacircncia Magneacuteticabull Natildeo deve ser mais utilizado como somente para
excluir causas secundaacuterias
bull Eacute um biomarcador de dano neuronal
bull Avaliar com cuidado atrofias assimeacutetricas
The n ew en g l an d j o u r n a l of med i c i n e
n engl j med 36423 nejmor g june 9 20112230
A Swedish study showed that subjects with mild
cognitive impairment who had low levels of
β-amyloid peptide 42 (Aβ42) and elevated levels
of tau protein in cerebrospinal f luid were sig-
nif icantly more likely to undergo progression to
Alzheimerrsquos disease than subjects without this
prof ile (hazard ratio 177 95 conf idence inter-
val 53 to 589) a similar relative risk of progres-
sion was associated with a low ratio of Aβ42 to
tau in the cerebrospinal f luid28 An international
multicenter study of 750 subjects with mild cogni-
tive impairment corroborated these general f ind-
ings2930 but used different cutoff points for ab-
normal f indings The reliability of these markers
is highly variable across laboratories standard-
ization will be needed before they are considered
for incorporation into routine care
The use of molecular imaging particularly of
amyloid plaques in the brain (Fig 3) has also been
studied as a possible approach to risk stratif ica-
tion31-33 In several studies subjects with mild cog-
nitive impairment in whom amyloid was detected
on positron-emission tomography (PET) with the
use of the amyloid-binding carbon 11ndashlabeled Pitts-
burgh compound B had more rapid progression to
Alzheimerrsquos disease than did subjects in whom
amyloid was not detected34 The rationale for using
this technique to predict disease progression is that
the presence of amyloid in a patient with mild
cognitive impairment is likely to indicate that the
patient has early Alzheimerrsquos disease however
amyloid has been detected on autopsy in clinical-
ly normal persons indicating that the predictive
value of this measure requires further study35
Management
From a clinical perspective patients with mild cog-
nitive impairment should not be labeled as having
early Alzheimerrsquos disease prodromal Alzheimerrsquos
disease or mild cognitive impairment of the Alz-
heimerrsquos disease type since the patient and fam-
ily are likely to hear only ―Alzheimerrsquos disease and
not appreciate the uncertainty of the association
with Alzheimerrsquos disease36 Clinicians should make
it clear that mild cognitive impairment is an abnor-
mal condition but that the precise outcome is not
certain
At present no medication intended for the
treatment of mild cognitive impairment has been
approved by the Food and Drug Administration
(FDA) In several placebo-controlled clinical trials
there was no signif icant reduction in rates of
progression to dementia among patients with
mild cognitive impairment who were treated with
agents used to treat Alzheimerrsquos disease (donepe-
zil galantamine and rivastigmine administered
at standard doses for Alzheimerrsquos disease for 2 to
4 years)537-40 In one trial evaluating the effects of
high-dose vitamin E (2000 IU daily) or donepezil
in persons with mild cognitive impairment do-
nep ezil signif icantly reduced the risk of pro-
gression to Alzheimerrsquos disease for the f irst 12
months of the study (and for up to 24 months in
the subgroup of subjects who were carriers of
APOE ε4) but had no signif icant effect on the
risk of Alz heimerrsquos disease at 36 months which
was the primary study outcome vitamin E did
not signif icantly reduce the risk of progression
at any time point assessed5
A B C
Figure 2 Coronal MRI Scans from Patients with Normal Cognition Mild Cognitive Impairment and Alzheimerrsquos
Disease
The arrows depict the hippocampal formations and the progressive atrophy characterizing the progression from nor-
mal cognition (Panel A) to mild cognitive impairment (Panel B) to Alzheimerrsquos disease (Panel C)
The New England Journal of Medicine
Downloaded from nejmorg at UECE on July 24 2016 For personal use only No other uses without permission
Copyright copy 2011 Massachusetts Medical Society All rights reserved
cl i n i cal pr act i ce
n engl j med 36423 nejmor g june 9 2011 2231
One potential explanation for the apparent lack
of eff icacy in the clinical trials of interventions in
persons with mild cognitive impairment mdash other
than a true absence of drug eff icacy mdash concerns
the heterogeneity of the subjects As the diagnos-
tic threshold moves to an earlier point in the clini-
cal spectrum of cognitive impairment the subtle
changes in cognition could be due to a variety of
causes other than a degenerative brain disease
making it diff icult to determine whether an inter-
vention has had a signif icant effect
There is some evidence of a potential benefit
from cognitive rehabilitation including the use of
mnemonics association strategies and computer-
assisted training programs4142 A recent systematic
review of the literature on cognitive rehabilitation
programs for persons with mild cognitive impair-
ment including some data from randomized clin-
ical trials showed signif icant improvement in
cognitive function at the end of training42
Observational data have shown associations
between the presence of cardiovascular risk factors
in patients with mild cognitive impairment and an
increased risk of progression to dementia7 Such
risk factors should be addressed although there
is no definitive evidence that modif ication of risk
factors slows disease progression In a randomized
trial that used the Cognitive Subscale of the Alz-
heimerrsquos Disease Assessment Scale to compare the
effect of a physical exercise program (brisk walking
for 150 minutes per week) with that of usual care
and education in persons with subjective memory
loss the exercise group had better cognitive func-
tion at 6 months (the primary study outcome) with
some residual benefit noted at 18 months43
Ar eas o f Un cer t ai n t y
More data are needed regarding the usefulness of
various potential predictors of progression to de-
mentia and their role in clinical practice Further
data on these concerns are awaited from the Alz-
heimerrsquos Disease Neuroimaging Initiative under
way in the United States and Canada2744 and from
similar ongoing studies in Japan Europe and Aus-
tralia Some of the goals of these studies are to
better understand the role of MRI f indings (eg
hippocampal atrophy)2245 f indings on 18FDG-PET
(patterns of hypometabolism in the brain) cere-
brospinal f luid markers (levels of Aβ42 and tau)
and f indings on molecular imaging (amyloid
plaques in the brain) in identifying the subgroup
of persons with amnestic mild cognitive impair-
ment who are likely to undergo progression to
clinical Alz hei merrsquos disease274647 Major challeng-
es are to determine optimal cutoff points for these
tests and to compare their relative reliability (alone
and in combination) Randomized trials are need-
ed to assess the potential benefits of pharmaco-
logic and lifestyle interventions in persons with
mild cognitive impairment who are predicted to
be at high risk for rapid progression to Alzheimerrsquos
A B C
Figure 3 Axial Scans of the Brain Obtained with Positron-Emission Tomography and the Use of Amyloid-Binding
Carbon 11ndashLabeled Pittsburgh Compound B
The yellow and red areas indicate retention of the amyloid-binding tracer reflecting amyloid deposits The patient
with normal cognition (Panel A) has no tracer retention whereas the patient with amnestic mild cognitive impair-
ment has an intermediate amount of tracer retention (Panel B) and the patient with Alzheimerrsquos disease has promi-
nent tracer retention (Panel C)
The New England Journal of Medicine
Downloaded from nejmorg at UECE on July 24 2016 For personal use only No other uses without permission
Copyright copy 2011 Massachusetts Medical Society All rights reserved
Outros Marcadores
bull Liacutequor
bull Dosagem de TAU (decaacuteda de 90)
bull Dosagem de AB-42
bull Growdon 1999 (AB-42 e TAU na DA)
Mattsson N et al 2009 JAMA
bull 750 pacientes com Comprometimento Cognitivo Leve
bull Seguimento por 2 anos
bull 271 evoluiram para DA
bull 59 apresentaram outras demecircncias
bull Baixos niacuteveis de Aβ-42 e altos de Fosfo-Tau com maior
acuraacutecia para evoluccedilatildeo para DA
bull 74 pacientes com Doenccedila de Alzheimer x 142 com
Comprometimento Cognitivo Leve e 82 controles
bull Hipometabolismo
- Precuneos
- Ciacutengulo Posterior
- Coacutertex Temporo-parietal
- Coacutertex Frontal
Koivunen et al Neurology 2011
bull 29 pacientes acompanhados por 2 anos
bull Avaliaccedilatildeo de PET com PIB e RM (Atrofia de
hipocampo)
bull 1729 converteram
bull Maior depoacutesito de PIB Ciacutengulo Posterior frontal lateral
temporal e putamem com maior atrofia
bull Pouca modificaccedilao no PIB em 2 anos
bull Aumento da atrofia
Hipoacutetese da Evoluccedilatildeo Temporal
dos processos fisiopatoloacutegicos
Biomarcador e CCL
Criteacuterios para Pesquisa DA
Porque utilizar biomarcador empacientes com quadros cognitivos
bull O paciente vai piorar dos sintomas cognitivos
bull Existe um processo patoloacutegico jaacute conhecido
bull Existe dano neuronal Topografia
bull Falsos positivos o que fazer
Ressonacircncia Magneacutetica de Cracircnio
bull Atrofia hipocampal
bull Casos leves ou assintomaacuteticos
bull Avaliaccedilatildeo de espessura cortical (Walhovd K et al 2010)
bull DTI (Sexton C et al 2011)
Ressonacircncia Magneacutetica
Vantagens
bull Disponibilidade
bull Visualizaccedilatildeo de atrofia
bull Possibilidade de vaacuterias mediccedilotildees
Limitaccedilotildees
bull Teacutecnicas habituaispoucos sensiacuteveis paraquadros leves
bull Reflete somente o danoneuronal
bull Teacutecnicas especiaispouca disponibilidade
Caso
bull RM laudo normal
PET-FDG
Vantagens
bull Sensibilidade
bull Reflete dano neuronal
Limitaccedilotildees
bull Custo
bull Sem ponto de corte
bull Natildeo especiacutefico do dano patoloacutegico
Caso
bull PET-FDG hipometabolismo FTP esquerdo e leve a Direita frontal e parietal
bull O que esse laudo mostra
bull Que eu consegui examinar e topografar direito
PET Amiloide
bull Dificuldades Iniciais
bull Marcador a base de Fluor
PET Tau and Amyloid-β Burden in Mild Alzheimers Disease Divergent Relationshipwith Age Cognition and Cerebrospinal Fluid BiomarkersKoychev I1 Gunn RN23 Firouzian A2 Lawson J1 Zamboni G1 Ridha B4 Sahakian BJ5 Rowe JB6 Thomas A7 Rochester L7 Ffytche D8 Howard R9 Zetterberg H9101112 MacKay C1 Lovestone S1 Deep and Frequent Phenotyping study team
J Alzheimers Dis 2017 Aug 8
PET Marcador Amiloacuteide
Vantagens
bull Refletem o processo patoloacutegico
bull Conseguem detectar indiviacuteduos assintomaacuteticos em risco
bull Predizem piora cliacutenica
Limitaccedilotildees
bull Custo
bull Disponibilidade
bull Normalizaccedilatildeo de pontos de corte
Caso
bull PET-Amiloacuteide
241 Estudos
11341 Pacientes
7086 Pacientes
Entatildeo vamos coletar Liacutequor para todos
Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory ClinicPatients in a Prospective CohortHandels RL12 Joore MA23 Vos SJ1 Aalten P1 Ramakers IH1 Rikkert MO4 Scheltens P5 Jansen WJ1 Visser PJ15 van Berckel BM5 van Domburg P6 Smid M7 Hoff E8 Hoogmoed J910 Bouwman F5 Claassen J4 Leentjens AF1 Wolfs CA1 Severens JL11 Verhey FR1Author information
bull 200 DA
bull 16 DA prodromica
bull 69 DFT
bull 59 DCB
bull 16 PSP
bull 44 DCL
bull 22 ACP
bull 41 Demecircncia Semacircntica
bull 52 Afasias logopecircnicas
bull 11 Afasias natildeo fluentes
bull 71 Depressatildeo
bull 49 Queixa subjetiva de memoacuteria
bull DA -100
bull DA prodromica-100
bull 439 dos outros pacientes tbpositivos
bull 818 ACP
bull 788 Afasia logopecircnica
bull 50 DCL
bull 458 DCB
bull 454 afasias natildeo fluentes
bull 366 demecircncia semacircnticas
bull 145 das DFT
bull 117 (Depressatildeo e QSM)
E o teste de Memoacuteria
bull Sensibilidade100
bull Especificidade de 748
bull Intrusotildees Sensibilidade de 83 e Especificidade72
bull 273 tinham deacuteficit hipocampal
bull 366 dos deprimidos
bull 40 DCL
bull 375 PSP
bull 319 DFT
bull 273 Afasia natildeo fluente
bull 227 ACP
bull 22 Demecircncia Semacircntica
bull 22 DCB
bull 58 Afasia logopecircnica
Existiu uma correlaccedilatildeo desempenho com os marcadores
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
O QUE Eacute UM BIOMARCADOR
bull Os biomarcadores podem ser definidos como umamedida objetiva e especiacutefica de um processo bioloacutegicoou patogecircnico podendo ser usados para avaliar o riscoou o prognoacutesticos da doenccedila guiar o diagnoacutesticocliacutenico ou monitorar intervenccedilotildees terapecircuticas
bull O biomarcador ideal deve detectar precocemente ecom grande precisatildeo uma caracteriacutesitca patoloacutegica dadoenccedila
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
Biomarcadores na praacutetica cliacutenica
bull Glicemia
bull FAN
bull Reaccedilatildeo de Wasserman ndash Siacutefilis
Detectar in vivo as alteraccedilotildees patoloacutegicas
Caso Cliacutenico
bull Ident MLR 59 anos economista
bull QP rdquoMovimentos Repetitivosrdquo
bull HDA Haacute dois anos movimentos repetitivos em matildeos
bull Deixou de dirigir ndash natildeo sabia tempo para passar marcha
bull Dificuldade em usar smartphone
Caso Cliacutenico
bull HPP cesariana depressatildeo
bull Med Desvenlafaxina 50mg Zolpiden 10mg
bull Haacutebitos etilismo leve
bull Alergia ndn
bull Hist Familiar Matildee com quadro demencial aos 62 anos
Avaliaccedilatildeo Cognitivabull ACE76100
atenccedilatildeo OT5 OE5 MI3 AC93-x-x-72-x=1518Memoacuteria1+6+4+6+5=2226FP peru pato pinto passaro preacutedio parque pneu=7FA galinha peru pato baleia cachorro gato peixe camaratildeo rato tartaruga passaros cavalo leatildeo=13(3+4=714)LIng1+3+1+2+1+1+10+2+1=2226V-E0+0+4+3+3=1016
Exame Neuroloacutegico
bull Equiliacutebrio movimentos em matildeo D e flexatildeoFM elevaccedilatildeo de MSD (levitaccedilatildeo e fica fazendo movimentos em MID)Reflexos Vivos
bull Apraxia evidente pior a DCoordenaccedilatildeo index nariz normal e leve disdiadococinesiaSensib Discreta anartestesia em MIDNC sem alteraccedilotildees
Hipoacutetese Diagnoacutestica
bull Degeneraccedilatildeo Cortico-Basal
bull Doenccedila de Alzheimer atiacutepica
E agora
Exames Complementares nas Demecircncias
bull Descartar causas secundaacuterias
bull Padrotildees especiacuteficos de atrofia
Nova Visatildeo
bull Diferenciaccedilatildeo dos tipos de demecircncia
bull Diagnoacutestico precoce
bull Marcador de evoluccedilatildeo
bull Resposta terapecircutica
Ressonacircncia Magneacuteticabull Natildeo deve ser mais utilizado como somente para
excluir causas secundaacuterias
bull Eacute um biomarcador de dano neuronal
bull Avaliar com cuidado atrofias assimeacutetricas
The n ew en g l an d j o u r n a l of med i c i n e
n engl j med 36423 nejmor g june 9 20112230
A Swedish study showed that subjects with mild
cognitive impairment who had low levels of
β-amyloid peptide 42 (Aβ42) and elevated levels
of tau protein in cerebrospinal f luid were sig-
nif icantly more likely to undergo progression to
Alzheimerrsquos disease than subjects without this
prof ile (hazard ratio 177 95 conf idence inter-
val 53 to 589) a similar relative risk of progres-
sion was associated with a low ratio of Aβ42 to
tau in the cerebrospinal f luid28 An international
multicenter study of 750 subjects with mild cogni-
tive impairment corroborated these general f ind-
ings2930 but used different cutoff points for ab-
normal f indings The reliability of these markers
is highly variable across laboratories standard-
ization will be needed before they are considered
for incorporation into routine care
The use of molecular imaging particularly of
amyloid plaques in the brain (Fig 3) has also been
studied as a possible approach to risk stratif ica-
tion31-33 In several studies subjects with mild cog-
nitive impairment in whom amyloid was detected
on positron-emission tomography (PET) with the
use of the amyloid-binding carbon 11ndashlabeled Pitts-
burgh compound B had more rapid progression to
Alzheimerrsquos disease than did subjects in whom
amyloid was not detected34 The rationale for using
this technique to predict disease progression is that
the presence of amyloid in a patient with mild
cognitive impairment is likely to indicate that the
patient has early Alzheimerrsquos disease however
amyloid has been detected on autopsy in clinical-
ly normal persons indicating that the predictive
value of this measure requires further study35
Management
From a clinical perspective patients with mild cog-
nitive impairment should not be labeled as having
early Alzheimerrsquos disease prodromal Alzheimerrsquos
disease or mild cognitive impairment of the Alz-
heimerrsquos disease type since the patient and fam-
ily are likely to hear only ―Alzheimerrsquos disease and
not appreciate the uncertainty of the association
with Alzheimerrsquos disease36 Clinicians should make
it clear that mild cognitive impairment is an abnor-
mal condition but that the precise outcome is not
certain
At present no medication intended for the
treatment of mild cognitive impairment has been
approved by the Food and Drug Administration
(FDA) In several placebo-controlled clinical trials
there was no signif icant reduction in rates of
progression to dementia among patients with
mild cognitive impairment who were treated with
agents used to treat Alzheimerrsquos disease (donepe-
zil galantamine and rivastigmine administered
at standard doses for Alzheimerrsquos disease for 2 to
4 years)537-40 In one trial evaluating the effects of
high-dose vitamin E (2000 IU daily) or donepezil
in persons with mild cognitive impairment do-
nep ezil signif icantly reduced the risk of pro-
gression to Alzheimerrsquos disease for the f irst 12
months of the study (and for up to 24 months in
the subgroup of subjects who were carriers of
APOE ε4) but had no signif icant effect on the
risk of Alz heimerrsquos disease at 36 months which
was the primary study outcome vitamin E did
not signif icantly reduce the risk of progression
at any time point assessed5
A B C
Figure 2 Coronal MRI Scans from Patients with Normal Cognition Mild Cognitive Impairment and Alzheimerrsquos
Disease
The arrows depict the hippocampal formations and the progressive atrophy characterizing the progression from nor-
mal cognition (Panel A) to mild cognitive impairment (Panel B) to Alzheimerrsquos disease (Panel C)
The New England Journal of Medicine
Downloaded from nejmorg at UECE on July 24 2016 For personal use only No other uses without permission
Copyright copy 2011 Massachusetts Medical Society All rights reserved
cl i n i cal pr act i ce
n engl j med 36423 nejmor g june 9 2011 2231
One potential explanation for the apparent lack
of eff icacy in the clinical trials of interventions in
persons with mild cognitive impairment mdash other
than a true absence of drug eff icacy mdash concerns
the heterogeneity of the subjects As the diagnos-
tic threshold moves to an earlier point in the clini-
cal spectrum of cognitive impairment the subtle
changes in cognition could be due to a variety of
causes other than a degenerative brain disease
making it diff icult to determine whether an inter-
vention has had a signif icant effect
There is some evidence of a potential benefit
from cognitive rehabilitation including the use of
mnemonics association strategies and computer-
assisted training programs4142 A recent systematic
review of the literature on cognitive rehabilitation
programs for persons with mild cognitive impair-
ment including some data from randomized clin-
ical trials showed signif icant improvement in
cognitive function at the end of training42
Observational data have shown associations
between the presence of cardiovascular risk factors
in patients with mild cognitive impairment and an
increased risk of progression to dementia7 Such
risk factors should be addressed although there
is no definitive evidence that modif ication of risk
factors slows disease progression In a randomized
trial that used the Cognitive Subscale of the Alz-
heimerrsquos Disease Assessment Scale to compare the
effect of a physical exercise program (brisk walking
for 150 minutes per week) with that of usual care
and education in persons with subjective memory
loss the exercise group had better cognitive func-
tion at 6 months (the primary study outcome) with
some residual benefit noted at 18 months43
Ar eas o f Un cer t ai n t y
More data are needed regarding the usefulness of
various potential predictors of progression to de-
mentia and their role in clinical practice Further
data on these concerns are awaited from the Alz-
heimerrsquos Disease Neuroimaging Initiative under
way in the United States and Canada2744 and from
similar ongoing studies in Japan Europe and Aus-
tralia Some of the goals of these studies are to
better understand the role of MRI f indings (eg
hippocampal atrophy)2245 f indings on 18FDG-PET
(patterns of hypometabolism in the brain) cere-
brospinal f luid markers (levels of Aβ42 and tau)
and f indings on molecular imaging (amyloid
plaques in the brain) in identifying the subgroup
of persons with amnestic mild cognitive impair-
ment who are likely to undergo progression to
clinical Alz hei merrsquos disease274647 Major challeng-
es are to determine optimal cutoff points for these
tests and to compare their relative reliability (alone
and in combination) Randomized trials are need-
ed to assess the potential benefits of pharmaco-
logic and lifestyle interventions in persons with
mild cognitive impairment who are predicted to
be at high risk for rapid progression to Alzheimerrsquos
A B C
Figure 3 Axial Scans of the Brain Obtained with Positron-Emission Tomography and the Use of Amyloid-Binding
Carbon 11ndashLabeled Pittsburgh Compound B
The yellow and red areas indicate retention of the amyloid-binding tracer reflecting amyloid deposits The patient
with normal cognition (Panel A) has no tracer retention whereas the patient with amnestic mild cognitive impair-
ment has an intermediate amount of tracer retention (Panel B) and the patient with Alzheimerrsquos disease has promi-
nent tracer retention (Panel C)
The New England Journal of Medicine
Downloaded from nejmorg at UECE on July 24 2016 For personal use only No other uses without permission
Copyright copy 2011 Massachusetts Medical Society All rights reserved
Outros Marcadores
bull Liacutequor
bull Dosagem de TAU (decaacuteda de 90)
bull Dosagem de AB-42
bull Growdon 1999 (AB-42 e TAU na DA)
Mattsson N et al 2009 JAMA
bull 750 pacientes com Comprometimento Cognitivo Leve
bull Seguimento por 2 anos
bull 271 evoluiram para DA
bull 59 apresentaram outras demecircncias
bull Baixos niacuteveis de Aβ-42 e altos de Fosfo-Tau com maior
acuraacutecia para evoluccedilatildeo para DA
bull 74 pacientes com Doenccedila de Alzheimer x 142 com
Comprometimento Cognitivo Leve e 82 controles
bull Hipometabolismo
- Precuneos
- Ciacutengulo Posterior
- Coacutertex Temporo-parietal
- Coacutertex Frontal
Koivunen et al Neurology 2011
bull 29 pacientes acompanhados por 2 anos
bull Avaliaccedilatildeo de PET com PIB e RM (Atrofia de
hipocampo)
bull 1729 converteram
bull Maior depoacutesito de PIB Ciacutengulo Posterior frontal lateral
temporal e putamem com maior atrofia
bull Pouca modificaccedilao no PIB em 2 anos
bull Aumento da atrofia
Hipoacutetese da Evoluccedilatildeo Temporal
dos processos fisiopatoloacutegicos
Biomarcador e CCL
Criteacuterios para Pesquisa DA
Porque utilizar biomarcador empacientes com quadros cognitivos
bull O paciente vai piorar dos sintomas cognitivos
bull Existe um processo patoloacutegico jaacute conhecido
bull Existe dano neuronal Topografia
bull Falsos positivos o que fazer
Ressonacircncia Magneacutetica de Cracircnio
bull Atrofia hipocampal
bull Casos leves ou assintomaacuteticos
bull Avaliaccedilatildeo de espessura cortical (Walhovd K et al 2010)
bull DTI (Sexton C et al 2011)
Ressonacircncia Magneacutetica
Vantagens
bull Disponibilidade
bull Visualizaccedilatildeo de atrofia
bull Possibilidade de vaacuterias mediccedilotildees
Limitaccedilotildees
bull Teacutecnicas habituaispoucos sensiacuteveis paraquadros leves
bull Reflete somente o danoneuronal
bull Teacutecnicas especiaispouca disponibilidade
Caso
bull RM laudo normal
PET-FDG
Vantagens
bull Sensibilidade
bull Reflete dano neuronal
Limitaccedilotildees
bull Custo
bull Sem ponto de corte
bull Natildeo especiacutefico do dano patoloacutegico
Caso
bull PET-FDG hipometabolismo FTP esquerdo e leve a Direita frontal e parietal
bull O que esse laudo mostra
bull Que eu consegui examinar e topografar direito
PET Amiloide
bull Dificuldades Iniciais
bull Marcador a base de Fluor
PET Tau and Amyloid-β Burden in Mild Alzheimers Disease Divergent Relationshipwith Age Cognition and Cerebrospinal Fluid BiomarkersKoychev I1 Gunn RN23 Firouzian A2 Lawson J1 Zamboni G1 Ridha B4 Sahakian BJ5 Rowe JB6 Thomas A7 Rochester L7 Ffytche D8 Howard R9 Zetterberg H9101112 MacKay C1 Lovestone S1 Deep and Frequent Phenotyping study team
J Alzheimers Dis 2017 Aug 8
PET Marcador Amiloacuteide
Vantagens
bull Refletem o processo patoloacutegico
bull Conseguem detectar indiviacuteduos assintomaacuteticos em risco
bull Predizem piora cliacutenica
Limitaccedilotildees
bull Custo
bull Disponibilidade
bull Normalizaccedilatildeo de pontos de corte
Caso
bull PET-Amiloacuteide
241 Estudos
11341 Pacientes
7086 Pacientes
Entatildeo vamos coletar Liacutequor para todos
Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory ClinicPatients in a Prospective CohortHandels RL12 Joore MA23 Vos SJ1 Aalten P1 Ramakers IH1 Rikkert MO4 Scheltens P5 Jansen WJ1 Visser PJ15 van Berckel BM5 van Domburg P6 Smid M7 Hoff E8 Hoogmoed J910 Bouwman F5 Claassen J4 Leentjens AF1 Wolfs CA1 Severens JL11 Verhey FR1Author information
bull 200 DA
bull 16 DA prodromica
bull 69 DFT
bull 59 DCB
bull 16 PSP
bull 44 DCL
bull 22 ACP
bull 41 Demecircncia Semacircntica
bull 52 Afasias logopecircnicas
bull 11 Afasias natildeo fluentes
bull 71 Depressatildeo
bull 49 Queixa subjetiva de memoacuteria
bull DA -100
bull DA prodromica-100
bull 439 dos outros pacientes tbpositivos
bull 818 ACP
bull 788 Afasia logopecircnica
bull 50 DCL
bull 458 DCB
bull 454 afasias natildeo fluentes
bull 366 demecircncia semacircnticas
bull 145 das DFT
bull 117 (Depressatildeo e QSM)
E o teste de Memoacuteria
bull Sensibilidade100
bull Especificidade de 748
bull Intrusotildees Sensibilidade de 83 e Especificidade72
bull 273 tinham deacuteficit hipocampal
bull 366 dos deprimidos
bull 40 DCL
bull 375 PSP
bull 319 DFT
bull 273 Afasia natildeo fluente
bull 227 ACP
bull 22 Demecircncia Semacircntica
bull 22 DCB
bull 58 Afasia logopecircnica
Existiu uma correlaccedilatildeo desempenho com os marcadores
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
Biomarcadores na praacutetica cliacutenica
bull Glicemia
bull FAN
bull Reaccedilatildeo de Wasserman ndash Siacutefilis
Detectar in vivo as alteraccedilotildees patoloacutegicas
Caso Cliacutenico
bull Ident MLR 59 anos economista
bull QP rdquoMovimentos Repetitivosrdquo
bull HDA Haacute dois anos movimentos repetitivos em matildeos
bull Deixou de dirigir ndash natildeo sabia tempo para passar marcha
bull Dificuldade em usar smartphone
Caso Cliacutenico
bull HPP cesariana depressatildeo
bull Med Desvenlafaxina 50mg Zolpiden 10mg
bull Haacutebitos etilismo leve
bull Alergia ndn
bull Hist Familiar Matildee com quadro demencial aos 62 anos
Avaliaccedilatildeo Cognitivabull ACE76100
atenccedilatildeo OT5 OE5 MI3 AC93-x-x-72-x=1518Memoacuteria1+6+4+6+5=2226FP peru pato pinto passaro preacutedio parque pneu=7FA galinha peru pato baleia cachorro gato peixe camaratildeo rato tartaruga passaros cavalo leatildeo=13(3+4=714)LIng1+3+1+2+1+1+10+2+1=2226V-E0+0+4+3+3=1016
Exame Neuroloacutegico
bull Equiliacutebrio movimentos em matildeo D e flexatildeoFM elevaccedilatildeo de MSD (levitaccedilatildeo e fica fazendo movimentos em MID)Reflexos Vivos
bull Apraxia evidente pior a DCoordenaccedilatildeo index nariz normal e leve disdiadococinesiaSensib Discreta anartestesia em MIDNC sem alteraccedilotildees
Hipoacutetese Diagnoacutestica
bull Degeneraccedilatildeo Cortico-Basal
bull Doenccedila de Alzheimer atiacutepica
E agora
Exames Complementares nas Demecircncias
bull Descartar causas secundaacuterias
bull Padrotildees especiacuteficos de atrofia
Nova Visatildeo
bull Diferenciaccedilatildeo dos tipos de demecircncia
bull Diagnoacutestico precoce
bull Marcador de evoluccedilatildeo
bull Resposta terapecircutica
Ressonacircncia Magneacuteticabull Natildeo deve ser mais utilizado como somente para
excluir causas secundaacuterias
bull Eacute um biomarcador de dano neuronal
bull Avaliar com cuidado atrofias assimeacutetricas
The n ew en g l an d j o u r n a l of med i c i n e
n engl j med 36423 nejmor g june 9 20112230
A Swedish study showed that subjects with mild
cognitive impairment who had low levels of
β-amyloid peptide 42 (Aβ42) and elevated levels
of tau protein in cerebrospinal f luid were sig-
nif icantly more likely to undergo progression to
Alzheimerrsquos disease than subjects without this
prof ile (hazard ratio 177 95 conf idence inter-
val 53 to 589) a similar relative risk of progres-
sion was associated with a low ratio of Aβ42 to
tau in the cerebrospinal f luid28 An international
multicenter study of 750 subjects with mild cogni-
tive impairment corroborated these general f ind-
ings2930 but used different cutoff points for ab-
normal f indings The reliability of these markers
is highly variable across laboratories standard-
ization will be needed before they are considered
for incorporation into routine care
The use of molecular imaging particularly of
amyloid plaques in the brain (Fig 3) has also been
studied as a possible approach to risk stratif ica-
tion31-33 In several studies subjects with mild cog-
nitive impairment in whom amyloid was detected
on positron-emission tomography (PET) with the
use of the amyloid-binding carbon 11ndashlabeled Pitts-
burgh compound B had more rapid progression to
Alzheimerrsquos disease than did subjects in whom
amyloid was not detected34 The rationale for using
this technique to predict disease progression is that
the presence of amyloid in a patient with mild
cognitive impairment is likely to indicate that the
patient has early Alzheimerrsquos disease however
amyloid has been detected on autopsy in clinical-
ly normal persons indicating that the predictive
value of this measure requires further study35
Management
From a clinical perspective patients with mild cog-
nitive impairment should not be labeled as having
early Alzheimerrsquos disease prodromal Alzheimerrsquos
disease or mild cognitive impairment of the Alz-
heimerrsquos disease type since the patient and fam-
ily are likely to hear only ―Alzheimerrsquos disease and
not appreciate the uncertainty of the association
with Alzheimerrsquos disease36 Clinicians should make
it clear that mild cognitive impairment is an abnor-
mal condition but that the precise outcome is not
certain
At present no medication intended for the
treatment of mild cognitive impairment has been
approved by the Food and Drug Administration
(FDA) In several placebo-controlled clinical trials
there was no signif icant reduction in rates of
progression to dementia among patients with
mild cognitive impairment who were treated with
agents used to treat Alzheimerrsquos disease (donepe-
zil galantamine and rivastigmine administered
at standard doses for Alzheimerrsquos disease for 2 to
4 years)537-40 In one trial evaluating the effects of
high-dose vitamin E (2000 IU daily) or donepezil
in persons with mild cognitive impairment do-
nep ezil signif icantly reduced the risk of pro-
gression to Alzheimerrsquos disease for the f irst 12
months of the study (and for up to 24 months in
the subgroup of subjects who were carriers of
APOE ε4) but had no signif icant effect on the
risk of Alz heimerrsquos disease at 36 months which
was the primary study outcome vitamin E did
not signif icantly reduce the risk of progression
at any time point assessed5
A B C
Figure 2 Coronal MRI Scans from Patients with Normal Cognition Mild Cognitive Impairment and Alzheimerrsquos
Disease
The arrows depict the hippocampal formations and the progressive atrophy characterizing the progression from nor-
mal cognition (Panel A) to mild cognitive impairment (Panel B) to Alzheimerrsquos disease (Panel C)
The New England Journal of Medicine
Downloaded from nejmorg at UECE on July 24 2016 For personal use only No other uses without permission
Copyright copy 2011 Massachusetts Medical Society All rights reserved
cl i n i cal pr act i ce
n engl j med 36423 nejmor g june 9 2011 2231
One potential explanation for the apparent lack
of eff icacy in the clinical trials of interventions in
persons with mild cognitive impairment mdash other
than a true absence of drug eff icacy mdash concerns
the heterogeneity of the subjects As the diagnos-
tic threshold moves to an earlier point in the clini-
cal spectrum of cognitive impairment the subtle
changes in cognition could be due to a variety of
causes other than a degenerative brain disease
making it diff icult to determine whether an inter-
vention has had a signif icant effect
There is some evidence of a potential benefit
from cognitive rehabilitation including the use of
mnemonics association strategies and computer-
assisted training programs4142 A recent systematic
review of the literature on cognitive rehabilitation
programs for persons with mild cognitive impair-
ment including some data from randomized clin-
ical trials showed signif icant improvement in
cognitive function at the end of training42
Observational data have shown associations
between the presence of cardiovascular risk factors
in patients with mild cognitive impairment and an
increased risk of progression to dementia7 Such
risk factors should be addressed although there
is no definitive evidence that modif ication of risk
factors slows disease progression In a randomized
trial that used the Cognitive Subscale of the Alz-
heimerrsquos Disease Assessment Scale to compare the
effect of a physical exercise program (brisk walking
for 150 minutes per week) with that of usual care
and education in persons with subjective memory
loss the exercise group had better cognitive func-
tion at 6 months (the primary study outcome) with
some residual benefit noted at 18 months43
Ar eas o f Un cer t ai n t y
More data are needed regarding the usefulness of
various potential predictors of progression to de-
mentia and their role in clinical practice Further
data on these concerns are awaited from the Alz-
heimerrsquos Disease Neuroimaging Initiative under
way in the United States and Canada2744 and from
similar ongoing studies in Japan Europe and Aus-
tralia Some of the goals of these studies are to
better understand the role of MRI f indings (eg
hippocampal atrophy)2245 f indings on 18FDG-PET
(patterns of hypometabolism in the brain) cere-
brospinal f luid markers (levels of Aβ42 and tau)
and f indings on molecular imaging (amyloid
plaques in the brain) in identifying the subgroup
of persons with amnestic mild cognitive impair-
ment who are likely to undergo progression to
clinical Alz hei merrsquos disease274647 Major challeng-
es are to determine optimal cutoff points for these
tests and to compare their relative reliability (alone
and in combination) Randomized trials are need-
ed to assess the potential benefits of pharmaco-
logic and lifestyle interventions in persons with
mild cognitive impairment who are predicted to
be at high risk for rapid progression to Alzheimerrsquos
A B C
Figure 3 Axial Scans of the Brain Obtained with Positron-Emission Tomography and the Use of Amyloid-Binding
Carbon 11ndashLabeled Pittsburgh Compound B
The yellow and red areas indicate retention of the amyloid-binding tracer reflecting amyloid deposits The patient
with normal cognition (Panel A) has no tracer retention whereas the patient with amnestic mild cognitive impair-
ment has an intermediate amount of tracer retention (Panel B) and the patient with Alzheimerrsquos disease has promi-
nent tracer retention (Panel C)
The New England Journal of Medicine
Downloaded from nejmorg at UECE on July 24 2016 For personal use only No other uses without permission
Copyright copy 2011 Massachusetts Medical Society All rights reserved
Outros Marcadores
bull Liacutequor
bull Dosagem de TAU (decaacuteda de 90)
bull Dosagem de AB-42
bull Growdon 1999 (AB-42 e TAU na DA)
Mattsson N et al 2009 JAMA
bull 750 pacientes com Comprometimento Cognitivo Leve
bull Seguimento por 2 anos
bull 271 evoluiram para DA
bull 59 apresentaram outras demecircncias
bull Baixos niacuteveis de Aβ-42 e altos de Fosfo-Tau com maior
acuraacutecia para evoluccedilatildeo para DA
bull 74 pacientes com Doenccedila de Alzheimer x 142 com
Comprometimento Cognitivo Leve e 82 controles
bull Hipometabolismo
- Precuneos
- Ciacutengulo Posterior
- Coacutertex Temporo-parietal
- Coacutertex Frontal
Koivunen et al Neurology 2011
bull 29 pacientes acompanhados por 2 anos
bull Avaliaccedilatildeo de PET com PIB e RM (Atrofia de
hipocampo)
bull 1729 converteram
bull Maior depoacutesito de PIB Ciacutengulo Posterior frontal lateral
temporal e putamem com maior atrofia
bull Pouca modificaccedilao no PIB em 2 anos
bull Aumento da atrofia
Hipoacutetese da Evoluccedilatildeo Temporal
dos processos fisiopatoloacutegicos
Biomarcador e CCL
Criteacuterios para Pesquisa DA
Porque utilizar biomarcador empacientes com quadros cognitivos
bull O paciente vai piorar dos sintomas cognitivos
bull Existe um processo patoloacutegico jaacute conhecido
bull Existe dano neuronal Topografia
bull Falsos positivos o que fazer
Ressonacircncia Magneacutetica de Cracircnio
bull Atrofia hipocampal
bull Casos leves ou assintomaacuteticos
bull Avaliaccedilatildeo de espessura cortical (Walhovd K et al 2010)
bull DTI (Sexton C et al 2011)
Ressonacircncia Magneacutetica
Vantagens
bull Disponibilidade
bull Visualizaccedilatildeo de atrofia
bull Possibilidade de vaacuterias mediccedilotildees
Limitaccedilotildees
bull Teacutecnicas habituaispoucos sensiacuteveis paraquadros leves
bull Reflete somente o danoneuronal
bull Teacutecnicas especiaispouca disponibilidade
Caso
bull RM laudo normal
PET-FDG
Vantagens
bull Sensibilidade
bull Reflete dano neuronal
Limitaccedilotildees
bull Custo
bull Sem ponto de corte
bull Natildeo especiacutefico do dano patoloacutegico
Caso
bull PET-FDG hipometabolismo FTP esquerdo e leve a Direita frontal e parietal
bull O que esse laudo mostra
bull Que eu consegui examinar e topografar direito
PET Amiloide
bull Dificuldades Iniciais
bull Marcador a base de Fluor
PET Tau and Amyloid-β Burden in Mild Alzheimers Disease Divergent Relationshipwith Age Cognition and Cerebrospinal Fluid BiomarkersKoychev I1 Gunn RN23 Firouzian A2 Lawson J1 Zamboni G1 Ridha B4 Sahakian BJ5 Rowe JB6 Thomas A7 Rochester L7 Ffytche D8 Howard R9 Zetterberg H9101112 MacKay C1 Lovestone S1 Deep and Frequent Phenotyping study team
J Alzheimers Dis 2017 Aug 8
PET Marcador Amiloacuteide
Vantagens
bull Refletem o processo patoloacutegico
bull Conseguem detectar indiviacuteduos assintomaacuteticos em risco
bull Predizem piora cliacutenica
Limitaccedilotildees
bull Custo
bull Disponibilidade
bull Normalizaccedilatildeo de pontos de corte
Caso
bull PET-Amiloacuteide
241 Estudos
11341 Pacientes
7086 Pacientes
Entatildeo vamos coletar Liacutequor para todos
Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory ClinicPatients in a Prospective CohortHandels RL12 Joore MA23 Vos SJ1 Aalten P1 Ramakers IH1 Rikkert MO4 Scheltens P5 Jansen WJ1 Visser PJ15 van Berckel BM5 van Domburg P6 Smid M7 Hoff E8 Hoogmoed J910 Bouwman F5 Claassen J4 Leentjens AF1 Wolfs CA1 Severens JL11 Verhey FR1Author information
bull 200 DA
bull 16 DA prodromica
bull 69 DFT
bull 59 DCB
bull 16 PSP
bull 44 DCL
bull 22 ACP
bull 41 Demecircncia Semacircntica
bull 52 Afasias logopecircnicas
bull 11 Afasias natildeo fluentes
bull 71 Depressatildeo
bull 49 Queixa subjetiva de memoacuteria
bull DA -100
bull DA prodromica-100
bull 439 dos outros pacientes tbpositivos
bull 818 ACP
bull 788 Afasia logopecircnica
bull 50 DCL
bull 458 DCB
bull 454 afasias natildeo fluentes
bull 366 demecircncia semacircnticas
bull 145 das DFT
bull 117 (Depressatildeo e QSM)
E o teste de Memoacuteria
bull Sensibilidade100
bull Especificidade de 748
bull Intrusotildees Sensibilidade de 83 e Especificidade72
bull 273 tinham deacuteficit hipocampal
bull 366 dos deprimidos
bull 40 DCL
bull 375 PSP
bull 319 DFT
bull 273 Afasia natildeo fluente
bull 227 ACP
bull 22 Demecircncia Semacircntica
bull 22 DCB
bull 58 Afasia logopecircnica
Existiu uma correlaccedilatildeo desempenho com os marcadores
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
Biomarcadores na praacutetica cliacutenica
bull Glicemia
bull FAN
bull Reaccedilatildeo de Wasserman ndash Siacutefilis
Detectar in vivo as alteraccedilotildees patoloacutegicas
Caso Cliacutenico
bull Ident MLR 59 anos economista
bull QP rdquoMovimentos Repetitivosrdquo
bull HDA Haacute dois anos movimentos repetitivos em matildeos
bull Deixou de dirigir ndash natildeo sabia tempo para passar marcha
bull Dificuldade em usar smartphone
Caso Cliacutenico
bull HPP cesariana depressatildeo
bull Med Desvenlafaxina 50mg Zolpiden 10mg
bull Haacutebitos etilismo leve
bull Alergia ndn
bull Hist Familiar Matildee com quadro demencial aos 62 anos
Avaliaccedilatildeo Cognitivabull ACE76100
atenccedilatildeo OT5 OE5 MI3 AC93-x-x-72-x=1518Memoacuteria1+6+4+6+5=2226FP peru pato pinto passaro preacutedio parque pneu=7FA galinha peru pato baleia cachorro gato peixe camaratildeo rato tartaruga passaros cavalo leatildeo=13(3+4=714)LIng1+3+1+2+1+1+10+2+1=2226V-E0+0+4+3+3=1016
Exame Neuroloacutegico
bull Equiliacutebrio movimentos em matildeo D e flexatildeoFM elevaccedilatildeo de MSD (levitaccedilatildeo e fica fazendo movimentos em MID)Reflexos Vivos
bull Apraxia evidente pior a DCoordenaccedilatildeo index nariz normal e leve disdiadococinesiaSensib Discreta anartestesia em MIDNC sem alteraccedilotildees
Hipoacutetese Diagnoacutestica
bull Degeneraccedilatildeo Cortico-Basal
bull Doenccedila de Alzheimer atiacutepica
E agora
Exames Complementares nas Demecircncias
bull Descartar causas secundaacuterias
bull Padrotildees especiacuteficos de atrofia
Nova Visatildeo
bull Diferenciaccedilatildeo dos tipos de demecircncia
bull Diagnoacutestico precoce
bull Marcador de evoluccedilatildeo
bull Resposta terapecircutica
Ressonacircncia Magneacuteticabull Natildeo deve ser mais utilizado como somente para
excluir causas secundaacuterias
bull Eacute um biomarcador de dano neuronal
bull Avaliar com cuidado atrofias assimeacutetricas
The n ew en g l an d j o u r n a l of med i c i n e
n engl j med 36423 nejmor g june 9 20112230
A Swedish study showed that subjects with mild
cognitive impairment who had low levels of
β-amyloid peptide 42 (Aβ42) and elevated levels
of tau protein in cerebrospinal f luid were sig-
nif icantly more likely to undergo progression to
Alzheimerrsquos disease than subjects without this
prof ile (hazard ratio 177 95 conf idence inter-
val 53 to 589) a similar relative risk of progres-
sion was associated with a low ratio of Aβ42 to
tau in the cerebrospinal f luid28 An international
multicenter study of 750 subjects with mild cogni-
tive impairment corroborated these general f ind-
ings2930 but used different cutoff points for ab-
normal f indings The reliability of these markers
is highly variable across laboratories standard-
ization will be needed before they are considered
for incorporation into routine care
The use of molecular imaging particularly of
amyloid plaques in the brain (Fig 3) has also been
studied as a possible approach to risk stratif ica-
tion31-33 In several studies subjects with mild cog-
nitive impairment in whom amyloid was detected
on positron-emission tomography (PET) with the
use of the amyloid-binding carbon 11ndashlabeled Pitts-
burgh compound B had more rapid progression to
Alzheimerrsquos disease than did subjects in whom
amyloid was not detected34 The rationale for using
this technique to predict disease progression is that
the presence of amyloid in a patient with mild
cognitive impairment is likely to indicate that the
patient has early Alzheimerrsquos disease however
amyloid has been detected on autopsy in clinical-
ly normal persons indicating that the predictive
value of this measure requires further study35
Management
From a clinical perspective patients with mild cog-
nitive impairment should not be labeled as having
early Alzheimerrsquos disease prodromal Alzheimerrsquos
disease or mild cognitive impairment of the Alz-
heimerrsquos disease type since the patient and fam-
ily are likely to hear only ―Alzheimerrsquos disease and
not appreciate the uncertainty of the association
with Alzheimerrsquos disease36 Clinicians should make
it clear that mild cognitive impairment is an abnor-
mal condition but that the precise outcome is not
certain
At present no medication intended for the
treatment of mild cognitive impairment has been
approved by the Food and Drug Administration
(FDA) In several placebo-controlled clinical trials
there was no signif icant reduction in rates of
progression to dementia among patients with
mild cognitive impairment who were treated with
agents used to treat Alzheimerrsquos disease (donepe-
zil galantamine and rivastigmine administered
at standard doses for Alzheimerrsquos disease for 2 to
4 years)537-40 In one trial evaluating the effects of
high-dose vitamin E (2000 IU daily) or donepezil
in persons with mild cognitive impairment do-
nep ezil signif icantly reduced the risk of pro-
gression to Alzheimerrsquos disease for the f irst 12
months of the study (and for up to 24 months in
the subgroup of subjects who were carriers of
APOE ε4) but had no signif icant effect on the
risk of Alz heimerrsquos disease at 36 months which
was the primary study outcome vitamin E did
not signif icantly reduce the risk of progression
at any time point assessed5
A B C
Figure 2 Coronal MRI Scans from Patients with Normal Cognition Mild Cognitive Impairment and Alzheimerrsquos
Disease
The arrows depict the hippocampal formations and the progressive atrophy characterizing the progression from nor-
mal cognition (Panel A) to mild cognitive impairment (Panel B) to Alzheimerrsquos disease (Panel C)
The New England Journal of Medicine
Downloaded from nejmorg at UECE on July 24 2016 For personal use only No other uses without permission
Copyright copy 2011 Massachusetts Medical Society All rights reserved
cl i n i cal pr act i ce
n engl j med 36423 nejmor g june 9 2011 2231
One potential explanation for the apparent lack
of eff icacy in the clinical trials of interventions in
persons with mild cognitive impairment mdash other
than a true absence of drug eff icacy mdash concerns
the heterogeneity of the subjects As the diagnos-
tic threshold moves to an earlier point in the clini-
cal spectrum of cognitive impairment the subtle
changes in cognition could be due to a variety of
causes other than a degenerative brain disease
making it diff icult to determine whether an inter-
vention has had a signif icant effect
There is some evidence of a potential benefit
from cognitive rehabilitation including the use of
mnemonics association strategies and computer-
assisted training programs4142 A recent systematic
review of the literature on cognitive rehabilitation
programs for persons with mild cognitive impair-
ment including some data from randomized clin-
ical trials showed signif icant improvement in
cognitive function at the end of training42
Observational data have shown associations
between the presence of cardiovascular risk factors
in patients with mild cognitive impairment and an
increased risk of progression to dementia7 Such
risk factors should be addressed although there
is no definitive evidence that modif ication of risk
factors slows disease progression In a randomized
trial that used the Cognitive Subscale of the Alz-
heimerrsquos Disease Assessment Scale to compare the
effect of a physical exercise program (brisk walking
for 150 minutes per week) with that of usual care
and education in persons with subjective memory
loss the exercise group had better cognitive func-
tion at 6 months (the primary study outcome) with
some residual benefit noted at 18 months43
Ar eas o f Un cer t ai n t y
More data are needed regarding the usefulness of
various potential predictors of progression to de-
mentia and their role in clinical practice Further
data on these concerns are awaited from the Alz-
heimerrsquos Disease Neuroimaging Initiative under
way in the United States and Canada2744 and from
similar ongoing studies in Japan Europe and Aus-
tralia Some of the goals of these studies are to
better understand the role of MRI f indings (eg
hippocampal atrophy)2245 f indings on 18FDG-PET
(patterns of hypometabolism in the brain) cere-
brospinal f luid markers (levels of Aβ42 and tau)
and f indings on molecular imaging (amyloid
plaques in the brain) in identifying the subgroup
of persons with amnestic mild cognitive impair-
ment who are likely to undergo progression to
clinical Alz hei merrsquos disease274647 Major challeng-
es are to determine optimal cutoff points for these
tests and to compare their relative reliability (alone
and in combination) Randomized trials are need-
ed to assess the potential benefits of pharmaco-
logic and lifestyle interventions in persons with
mild cognitive impairment who are predicted to
be at high risk for rapid progression to Alzheimerrsquos
A B C
Figure 3 Axial Scans of the Brain Obtained with Positron-Emission Tomography and the Use of Amyloid-Binding
Carbon 11ndashLabeled Pittsburgh Compound B
The yellow and red areas indicate retention of the amyloid-binding tracer reflecting amyloid deposits The patient
with normal cognition (Panel A) has no tracer retention whereas the patient with amnestic mild cognitive impair-
ment has an intermediate amount of tracer retention (Panel B) and the patient with Alzheimerrsquos disease has promi-
nent tracer retention (Panel C)
The New England Journal of Medicine
Downloaded from nejmorg at UECE on July 24 2016 For personal use only No other uses without permission
Copyright copy 2011 Massachusetts Medical Society All rights reserved
Outros Marcadores
bull Liacutequor
bull Dosagem de TAU (decaacuteda de 90)
bull Dosagem de AB-42
bull Growdon 1999 (AB-42 e TAU na DA)
Mattsson N et al 2009 JAMA
bull 750 pacientes com Comprometimento Cognitivo Leve
bull Seguimento por 2 anos
bull 271 evoluiram para DA
bull 59 apresentaram outras demecircncias
bull Baixos niacuteveis de Aβ-42 e altos de Fosfo-Tau com maior
acuraacutecia para evoluccedilatildeo para DA
bull 74 pacientes com Doenccedila de Alzheimer x 142 com
Comprometimento Cognitivo Leve e 82 controles
bull Hipometabolismo
- Precuneos
- Ciacutengulo Posterior
- Coacutertex Temporo-parietal
- Coacutertex Frontal
Koivunen et al Neurology 2011
bull 29 pacientes acompanhados por 2 anos
bull Avaliaccedilatildeo de PET com PIB e RM (Atrofia de
hipocampo)
bull 1729 converteram
bull Maior depoacutesito de PIB Ciacutengulo Posterior frontal lateral
temporal e putamem com maior atrofia
bull Pouca modificaccedilao no PIB em 2 anos
bull Aumento da atrofia
Hipoacutetese da Evoluccedilatildeo Temporal
dos processos fisiopatoloacutegicos
Biomarcador e CCL
Criteacuterios para Pesquisa DA
Porque utilizar biomarcador empacientes com quadros cognitivos
bull O paciente vai piorar dos sintomas cognitivos
bull Existe um processo patoloacutegico jaacute conhecido
bull Existe dano neuronal Topografia
bull Falsos positivos o que fazer
Ressonacircncia Magneacutetica de Cracircnio
bull Atrofia hipocampal
bull Casos leves ou assintomaacuteticos
bull Avaliaccedilatildeo de espessura cortical (Walhovd K et al 2010)
bull DTI (Sexton C et al 2011)
Ressonacircncia Magneacutetica
Vantagens
bull Disponibilidade
bull Visualizaccedilatildeo de atrofia
bull Possibilidade de vaacuterias mediccedilotildees
Limitaccedilotildees
bull Teacutecnicas habituaispoucos sensiacuteveis paraquadros leves
bull Reflete somente o danoneuronal
bull Teacutecnicas especiaispouca disponibilidade
Caso
bull RM laudo normal
PET-FDG
Vantagens
bull Sensibilidade
bull Reflete dano neuronal
Limitaccedilotildees
bull Custo
bull Sem ponto de corte
bull Natildeo especiacutefico do dano patoloacutegico
Caso
bull PET-FDG hipometabolismo FTP esquerdo e leve a Direita frontal e parietal
bull O que esse laudo mostra
bull Que eu consegui examinar e topografar direito
PET Amiloide
bull Dificuldades Iniciais
bull Marcador a base de Fluor
PET Tau and Amyloid-β Burden in Mild Alzheimers Disease Divergent Relationshipwith Age Cognition and Cerebrospinal Fluid BiomarkersKoychev I1 Gunn RN23 Firouzian A2 Lawson J1 Zamboni G1 Ridha B4 Sahakian BJ5 Rowe JB6 Thomas A7 Rochester L7 Ffytche D8 Howard R9 Zetterberg H9101112 MacKay C1 Lovestone S1 Deep and Frequent Phenotyping study team
J Alzheimers Dis 2017 Aug 8
PET Marcador Amiloacuteide
Vantagens
bull Refletem o processo patoloacutegico
bull Conseguem detectar indiviacuteduos assintomaacuteticos em risco
bull Predizem piora cliacutenica
Limitaccedilotildees
bull Custo
bull Disponibilidade
bull Normalizaccedilatildeo de pontos de corte
Caso
bull PET-Amiloacuteide
241 Estudos
11341 Pacientes
7086 Pacientes
Entatildeo vamos coletar Liacutequor para todos
Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory ClinicPatients in a Prospective CohortHandels RL12 Joore MA23 Vos SJ1 Aalten P1 Ramakers IH1 Rikkert MO4 Scheltens P5 Jansen WJ1 Visser PJ15 van Berckel BM5 van Domburg P6 Smid M7 Hoff E8 Hoogmoed J910 Bouwman F5 Claassen J4 Leentjens AF1 Wolfs CA1 Severens JL11 Verhey FR1Author information
bull 200 DA
bull 16 DA prodromica
bull 69 DFT
bull 59 DCB
bull 16 PSP
bull 44 DCL
bull 22 ACP
bull 41 Demecircncia Semacircntica
bull 52 Afasias logopecircnicas
bull 11 Afasias natildeo fluentes
bull 71 Depressatildeo
bull 49 Queixa subjetiva de memoacuteria
bull DA -100
bull DA prodromica-100
bull 439 dos outros pacientes tbpositivos
bull 818 ACP
bull 788 Afasia logopecircnica
bull 50 DCL
bull 458 DCB
bull 454 afasias natildeo fluentes
bull 366 demecircncia semacircnticas
bull 145 das DFT
bull 117 (Depressatildeo e QSM)
E o teste de Memoacuteria
bull Sensibilidade100
bull Especificidade de 748
bull Intrusotildees Sensibilidade de 83 e Especificidade72
bull 273 tinham deacuteficit hipocampal
bull 366 dos deprimidos
bull 40 DCL
bull 375 PSP
bull 319 DFT
bull 273 Afasia natildeo fluente
bull 227 ACP
bull 22 Demecircncia Semacircntica
bull 22 DCB
bull 58 Afasia logopecircnica
Existiu uma correlaccedilatildeo desempenho com os marcadores
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
Detectar in vivo as alteraccedilotildees patoloacutegicas
Caso Cliacutenico
bull Ident MLR 59 anos economista
bull QP rdquoMovimentos Repetitivosrdquo
bull HDA Haacute dois anos movimentos repetitivos em matildeos
bull Deixou de dirigir ndash natildeo sabia tempo para passar marcha
bull Dificuldade em usar smartphone
Caso Cliacutenico
bull HPP cesariana depressatildeo
bull Med Desvenlafaxina 50mg Zolpiden 10mg
bull Haacutebitos etilismo leve
bull Alergia ndn
bull Hist Familiar Matildee com quadro demencial aos 62 anos
Avaliaccedilatildeo Cognitivabull ACE76100
atenccedilatildeo OT5 OE5 MI3 AC93-x-x-72-x=1518Memoacuteria1+6+4+6+5=2226FP peru pato pinto passaro preacutedio parque pneu=7FA galinha peru pato baleia cachorro gato peixe camaratildeo rato tartaruga passaros cavalo leatildeo=13(3+4=714)LIng1+3+1+2+1+1+10+2+1=2226V-E0+0+4+3+3=1016
Exame Neuroloacutegico
bull Equiliacutebrio movimentos em matildeo D e flexatildeoFM elevaccedilatildeo de MSD (levitaccedilatildeo e fica fazendo movimentos em MID)Reflexos Vivos
bull Apraxia evidente pior a DCoordenaccedilatildeo index nariz normal e leve disdiadococinesiaSensib Discreta anartestesia em MIDNC sem alteraccedilotildees
Hipoacutetese Diagnoacutestica
bull Degeneraccedilatildeo Cortico-Basal
bull Doenccedila de Alzheimer atiacutepica
E agora
Exames Complementares nas Demecircncias
bull Descartar causas secundaacuterias
bull Padrotildees especiacuteficos de atrofia
Nova Visatildeo
bull Diferenciaccedilatildeo dos tipos de demecircncia
bull Diagnoacutestico precoce
bull Marcador de evoluccedilatildeo
bull Resposta terapecircutica
Ressonacircncia Magneacuteticabull Natildeo deve ser mais utilizado como somente para
excluir causas secundaacuterias
bull Eacute um biomarcador de dano neuronal
bull Avaliar com cuidado atrofias assimeacutetricas
The n ew en g l an d j o u r n a l of med i c i n e
n engl j med 36423 nejmor g june 9 20112230
A Swedish study showed that subjects with mild
cognitive impairment who had low levels of
β-amyloid peptide 42 (Aβ42) and elevated levels
of tau protein in cerebrospinal f luid were sig-
nif icantly more likely to undergo progression to
Alzheimerrsquos disease than subjects without this
prof ile (hazard ratio 177 95 conf idence inter-
val 53 to 589) a similar relative risk of progres-
sion was associated with a low ratio of Aβ42 to
tau in the cerebrospinal f luid28 An international
multicenter study of 750 subjects with mild cogni-
tive impairment corroborated these general f ind-
ings2930 but used different cutoff points for ab-
normal f indings The reliability of these markers
is highly variable across laboratories standard-
ization will be needed before they are considered
for incorporation into routine care
The use of molecular imaging particularly of
amyloid plaques in the brain (Fig 3) has also been
studied as a possible approach to risk stratif ica-
tion31-33 In several studies subjects with mild cog-
nitive impairment in whom amyloid was detected
on positron-emission tomography (PET) with the
use of the amyloid-binding carbon 11ndashlabeled Pitts-
burgh compound B had more rapid progression to
Alzheimerrsquos disease than did subjects in whom
amyloid was not detected34 The rationale for using
this technique to predict disease progression is that
the presence of amyloid in a patient with mild
cognitive impairment is likely to indicate that the
patient has early Alzheimerrsquos disease however
amyloid has been detected on autopsy in clinical-
ly normal persons indicating that the predictive
value of this measure requires further study35
Management
From a clinical perspective patients with mild cog-
nitive impairment should not be labeled as having
early Alzheimerrsquos disease prodromal Alzheimerrsquos
disease or mild cognitive impairment of the Alz-
heimerrsquos disease type since the patient and fam-
ily are likely to hear only ―Alzheimerrsquos disease and
not appreciate the uncertainty of the association
with Alzheimerrsquos disease36 Clinicians should make
it clear that mild cognitive impairment is an abnor-
mal condition but that the precise outcome is not
certain
At present no medication intended for the
treatment of mild cognitive impairment has been
approved by the Food and Drug Administration
(FDA) In several placebo-controlled clinical trials
there was no signif icant reduction in rates of
progression to dementia among patients with
mild cognitive impairment who were treated with
agents used to treat Alzheimerrsquos disease (donepe-
zil galantamine and rivastigmine administered
at standard doses for Alzheimerrsquos disease for 2 to
4 years)537-40 In one trial evaluating the effects of
high-dose vitamin E (2000 IU daily) or donepezil
in persons with mild cognitive impairment do-
nep ezil signif icantly reduced the risk of pro-
gression to Alzheimerrsquos disease for the f irst 12
months of the study (and for up to 24 months in
the subgroup of subjects who were carriers of
APOE ε4) but had no signif icant effect on the
risk of Alz heimerrsquos disease at 36 months which
was the primary study outcome vitamin E did
not signif icantly reduce the risk of progression
at any time point assessed5
A B C
Figure 2 Coronal MRI Scans from Patients with Normal Cognition Mild Cognitive Impairment and Alzheimerrsquos
Disease
The arrows depict the hippocampal formations and the progressive atrophy characterizing the progression from nor-
mal cognition (Panel A) to mild cognitive impairment (Panel B) to Alzheimerrsquos disease (Panel C)
The New England Journal of Medicine
Downloaded from nejmorg at UECE on July 24 2016 For personal use only No other uses without permission
Copyright copy 2011 Massachusetts Medical Society All rights reserved
cl i n i cal pr act i ce
n engl j med 36423 nejmor g june 9 2011 2231
One potential explanation for the apparent lack
of eff icacy in the clinical trials of interventions in
persons with mild cognitive impairment mdash other
than a true absence of drug eff icacy mdash concerns
the heterogeneity of the subjects As the diagnos-
tic threshold moves to an earlier point in the clini-
cal spectrum of cognitive impairment the subtle
changes in cognition could be due to a variety of
causes other than a degenerative brain disease
making it diff icult to determine whether an inter-
vention has had a signif icant effect
There is some evidence of a potential benefit
from cognitive rehabilitation including the use of
mnemonics association strategies and computer-
assisted training programs4142 A recent systematic
review of the literature on cognitive rehabilitation
programs for persons with mild cognitive impair-
ment including some data from randomized clin-
ical trials showed signif icant improvement in
cognitive function at the end of training42
Observational data have shown associations
between the presence of cardiovascular risk factors
in patients with mild cognitive impairment and an
increased risk of progression to dementia7 Such
risk factors should be addressed although there
is no definitive evidence that modif ication of risk
factors slows disease progression In a randomized
trial that used the Cognitive Subscale of the Alz-
heimerrsquos Disease Assessment Scale to compare the
effect of a physical exercise program (brisk walking
for 150 minutes per week) with that of usual care
and education in persons with subjective memory
loss the exercise group had better cognitive func-
tion at 6 months (the primary study outcome) with
some residual benefit noted at 18 months43
Ar eas o f Un cer t ai n t y
More data are needed regarding the usefulness of
various potential predictors of progression to de-
mentia and their role in clinical practice Further
data on these concerns are awaited from the Alz-
heimerrsquos Disease Neuroimaging Initiative under
way in the United States and Canada2744 and from
similar ongoing studies in Japan Europe and Aus-
tralia Some of the goals of these studies are to
better understand the role of MRI f indings (eg
hippocampal atrophy)2245 f indings on 18FDG-PET
(patterns of hypometabolism in the brain) cere-
brospinal f luid markers (levels of Aβ42 and tau)
and f indings on molecular imaging (amyloid
plaques in the brain) in identifying the subgroup
of persons with amnestic mild cognitive impair-
ment who are likely to undergo progression to
clinical Alz hei merrsquos disease274647 Major challeng-
es are to determine optimal cutoff points for these
tests and to compare their relative reliability (alone
and in combination) Randomized trials are need-
ed to assess the potential benefits of pharmaco-
logic and lifestyle interventions in persons with
mild cognitive impairment who are predicted to
be at high risk for rapid progression to Alzheimerrsquos
A B C
Figure 3 Axial Scans of the Brain Obtained with Positron-Emission Tomography and the Use of Amyloid-Binding
Carbon 11ndashLabeled Pittsburgh Compound B
The yellow and red areas indicate retention of the amyloid-binding tracer reflecting amyloid deposits The patient
with normal cognition (Panel A) has no tracer retention whereas the patient with amnestic mild cognitive impair-
ment has an intermediate amount of tracer retention (Panel B) and the patient with Alzheimerrsquos disease has promi-
nent tracer retention (Panel C)
The New England Journal of Medicine
Downloaded from nejmorg at UECE on July 24 2016 For personal use only No other uses without permission
Copyright copy 2011 Massachusetts Medical Society All rights reserved
Outros Marcadores
bull Liacutequor
bull Dosagem de TAU (decaacuteda de 90)
bull Dosagem de AB-42
bull Growdon 1999 (AB-42 e TAU na DA)
Mattsson N et al 2009 JAMA
bull 750 pacientes com Comprometimento Cognitivo Leve
bull Seguimento por 2 anos
bull 271 evoluiram para DA
bull 59 apresentaram outras demecircncias
bull Baixos niacuteveis de Aβ-42 e altos de Fosfo-Tau com maior
acuraacutecia para evoluccedilatildeo para DA
bull 74 pacientes com Doenccedila de Alzheimer x 142 com
Comprometimento Cognitivo Leve e 82 controles
bull Hipometabolismo
- Precuneos
- Ciacutengulo Posterior
- Coacutertex Temporo-parietal
- Coacutertex Frontal
Koivunen et al Neurology 2011
bull 29 pacientes acompanhados por 2 anos
bull Avaliaccedilatildeo de PET com PIB e RM (Atrofia de
hipocampo)
bull 1729 converteram
bull Maior depoacutesito de PIB Ciacutengulo Posterior frontal lateral
temporal e putamem com maior atrofia
bull Pouca modificaccedilao no PIB em 2 anos
bull Aumento da atrofia
Hipoacutetese da Evoluccedilatildeo Temporal
dos processos fisiopatoloacutegicos
Biomarcador e CCL
Criteacuterios para Pesquisa DA
Porque utilizar biomarcador empacientes com quadros cognitivos
bull O paciente vai piorar dos sintomas cognitivos
bull Existe um processo patoloacutegico jaacute conhecido
bull Existe dano neuronal Topografia
bull Falsos positivos o que fazer
Ressonacircncia Magneacutetica de Cracircnio
bull Atrofia hipocampal
bull Casos leves ou assintomaacuteticos
bull Avaliaccedilatildeo de espessura cortical (Walhovd K et al 2010)
bull DTI (Sexton C et al 2011)
Ressonacircncia Magneacutetica
Vantagens
bull Disponibilidade
bull Visualizaccedilatildeo de atrofia
bull Possibilidade de vaacuterias mediccedilotildees
Limitaccedilotildees
bull Teacutecnicas habituaispoucos sensiacuteveis paraquadros leves
bull Reflete somente o danoneuronal
bull Teacutecnicas especiaispouca disponibilidade
Caso
bull RM laudo normal
PET-FDG
Vantagens
bull Sensibilidade
bull Reflete dano neuronal
Limitaccedilotildees
bull Custo
bull Sem ponto de corte
bull Natildeo especiacutefico do dano patoloacutegico
Caso
bull PET-FDG hipometabolismo FTP esquerdo e leve a Direita frontal e parietal
bull O que esse laudo mostra
bull Que eu consegui examinar e topografar direito
PET Amiloide
bull Dificuldades Iniciais
bull Marcador a base de Fluor
PET Tau and Amyloid-β Burden in Mild Alzheimers Disease Divergent Relationshipwith Age Cognition and Cerebrospinal Fluid BiomarkersKoychev I1 Gunn RN23 Firouzian A2 Lawson J1 Zamboni G1 Ridha B4 Sahakian BJ5 Rowe JB6 Thomas A7 Rochester L7 Ffytche D8 Howard R9 Zetterberg H9101112 MacKay C1 Lovestone S1 Deep and Frequent Phenotyping study team
J Alzheimers Dis 2017 Aug 8
PET Marcador Amiloacuteide
Vantagens
bull Refletem o processo patoloacutegico
bull Conseguem detectar indiviacuteduos assintomaacuteticos em risco
bull Predizem piora cliacutenica
Limitaccedilotildees
bull Custo
bull Disponibilidade
bull Normalizaccedilatildeo de pontos de corte
Caso
bull PET-Amiloacuteide
241 Estudos
11341 Pacientes
7086 Pacientes
Entatildeo vamos coletar Liacutequor para todos
Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory ClinicPatients in a Prospective CohortHandels RL12 Joore MA23 Vos SJ1 Aalten P1 Ramakers IH1 Rikkert MO4 Scheltens P5 Jansen WJ1 Visser PJ15 van Berckel BM5 van Domburg P6 Smid M7 Hoff E8 Hoogmoed J910 Bouwman F5 Claassen J4 Leentjens AF1 Wolfs CA1 Severens JL11 Verhey FR1Author information
bull 200 DA
bull 16 DA prodromica
bull 69 DFT
bull 59 DCB
bull 16 PSP
bull 44 DCL
bull 22 ACP
bull 41 Demecircncia Semacircntica
bull 52 Afasias logopecircnicas
bull 11 Afasias natildeo fluentes
bull 71 Depressatildeo
bull 49 Queixa subjetiva de memoacuteria
bull DA -100
bull DA prodromica-100
bull 439 dos outros pacientes tbpositivos
bull 818 ACP
bull 788 Afasia logopecircnica
bull 50 DCL
bull 458 DCB
bull 454 afasias natildeo fluentes
bull 366 demecircncia semacircnticas
bull 145 das DFT
bull 117 (Depressatildeo e QSM)
E o teste de Memoacuteria
bull Sensibilidade100
bull Especificidade de 748
bull Intrusotildees Sensibilidade de 83 e Especificidade72
bull 273 tinham deacuteficit hipocampal
bull 366 dos deprimidos
bull 40 DCL
bull 375 PSP
bull 319 DFT
bull 273 Afasia natildeo fluente
bull 227 ACP
bull 22 Demecircncia Semacircntica
bull 22 DCB
bull 58 Afasia logopecircnica
Existiu uma correlaccedilatildeo desempenho com os marcadores
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
Caso Cliacutenico
bull Ident MLR 59 anos economista
bull QP rdquoMovimentos Repetitivosrdquo
bull HDA Haacute dois anos movimentos repetitivos em matildeos
bull Deixou de dirigir ndash natildeo sabia tempo para passar marcha
bull Dificuldade em usar smartphone
Caso Cliacutenico
bull HPP cesariana depressatildeo
bull Med Desvenlafaxina 50mg Zolpiden 10mg
bull Haacutebitos etilismo leve
bull Alergia ndn
bull Hist Familiar Matildee com quadro demencial aos 62 anos
Avaliaccedilatildeo Cognitivabull ACE76100
atenccedilatildeo OT5 OE5 MI3 AC93-x-x-72-x=1518Memoacuteria1+6+4+6+5=2226FP peru pato pinto passaro preacutedio parque pneu=7FA galinha peru pato baleia cachorro gato peixe camaratildeo rato tartaruga passaros cavalo leatildeo=13(3+4=714)LIng1+3+1+2+1+1+10+2+1=2226V-E0+0+4+3+3=1016
Exame Neuroloacutegico
bull Equiliacutebrio movimentos em matildeo D e flexatildeoFM elevaccedilatildeo de MSD (levitaccedilatildeo e fica fazendo movimentos em MID)Reflexos Vivos
bull Apraxia evidente pior a DCoordenaccedilatildeo index nariz normal e leve disdiadococinesiaSensib Discreta anartestesia em MIDNC sem alteraccedilotildees
Hipoacutetese Diagnoacutestica
bull Degeneraccedilatildeo Cortico-Basal
bull Doenccedila de Alzheimer atiacutepica
E agora
Exames Complementares nas Demecircncias
bull Descartar causas secundaacuterias
bull Padrotildees especiacuteficos de atrofia
Nova Visatildeo
bull Diferenciaccedilatildeo dos tipos de demecircncia
bull Diagnoacutestico precoce
bull Marcador de evoluccedilatildeo
bull Resposta terapecircutica
Ressonacircncia Magneacuteticabull Natildeo deve ser mais utilizado como somente para
excluir causas secundaacuterias
bull Eacute um biomarcador de dano neuronal
bull Avaliar com cuidado atrofias assimeacutetricas
The n ew en g l an d j o u r n a l of med i c i n e
n engl j med 36423 nejmor g june 9 20112230
A Swedish study showed that subjects with mild
cognitive impairment who had low levels of
β-amyloid peptide 42 (Aβ42) and elevated levels
of tau protein in cerebrospinal f luid were sig-
nif icantly more likely to undergo progression to
Alzheimerrsquos disease than subjects without this
prof ile (hazard ratio 177 95 conf idence inter-
val 53 to 589) a similar relative risk of progres-
sion was associated with a low ratio of Aβ42 to
tau in the cerebrospinal f luid28 An international
multicenter study of 750 subjects with mild cogni-
tive impairment corroborated these general f ind-
ings2930 but used different cutoff points for ab-
normal f indings The reliability of these markers
is highly variable across laboratories standard-
ization will be needed before they are considered
for incorporation into routine care
The use of molecular imaging particularly of
amyloid plaques in the brain (Fig 3) has also been
studied as a possible approach to risk stratif ica-
tion31-33 In several studies subjects with mild cog-
nitive impairment in whom amyloid was detected
on positron-emission tomography (PET) with the
use of the amyloid-binding carbon 11ndashlabeled Pitts-
burgh compound B had more rapid progression to
Alzheimerrsquos disease than did subjects in whom
amyloid was not detected34 The rationale for using
this technique to predict disease progression is that
the presence of amyloid in a patient with mild
cognitive impairment is likely to indicate that the
patient has early Alzheimerrsquos disease however
amyloid has been detected on autopsy in clinical-
ly normal persons indicating that the predictive
value of this measure requires further study35
Management
From a clinical perspective patients with mild cog-
nitive impairment should not be labeled as having
early Alzheimerrsquos disease prodromal Alzheimerrsquos
disease or mild cognitive impairment of the Alz-
heimerrsquos disease type since the patient and fam-
ily are likely to hear only ―Alzheimerrsquos disease and
not appreciate the uncertainty of the association
with Alzheimerrsquos disease36 Clinicians should make
it clear that mild cognitive impairment is an abnor-
mal condition but that the precise outcome is not
certain
At present no medication intended for the
treatment of mild cognitive impairment has been
approved by the Food and Drug Administration
(FDA) In several placebo-controlled clinical trials
there was no signif icant reduction in rates of
progression to dementia among patients with
mild cognitive impairment who were treated with
agents used to treat Alzheimerrsquos disease (donepe-
zil galantamine and rivastigmine administered
at standard doses for Alzheimerrsquos disease for 2 to
4 years)537-40 In one trial evaluating the effects of
high-dose vitamin E (2000 IU daily) or donepezil
in persons with mild cognitive impairment do-
nep ezil signif icantly reduced the risk of pro-
gression to Alzheimerrsquos disease for the f irst 12
months of the study (and for up to 24 months in
the subgroup of subjects who were carriers of
APOE ε4) but had no signif icant effect on the
risk of Alz heimerrsquos disease at 36 months which
was the primary study outcome vitamin E did
not signif icantly reduce the risk of progression
at any time point assessed5
A B C
Figure 2 Coronal MRI Scans from Patients with Normal Cognition Mild Cognitive Impairment and Alzheimerrsquos
Disease
The arrows depict the hippocampal formations and the progressive atrophy characterizing the progression from nor-
mal cognition (Panel A) to mild cognitive impairment (Panel B) to Alzheimerrsquos disease (Panel C)
The New England Journal of Medicine
Downloaded from nejmorg at UECE on July 24 2016 For personal use only No other uses without permission
Copyright copy 2011 Massachusetts Medical Society All rights reserved
cl i n i cal pr act i ce
n engl j med 36423 nejmor g june 9 2011 2231
One potential explanation for the apparent lack
of eff icacy in the clinical trials of interventions in
persons with mild cognitive impairment mdash other
than a true absence of drug eff icacy mdash concerns
the heterogeneity of the subjects As the diagnos-
tic threshold moves to an earlier point in the clini-
cal spectrum of cognitive impairment the subtle
changes in cognition could be due to a variety of
causes other than a degenerative brain disease
making it diff icult to determine whether an inter-
vention has had a signif icant effect
There is some evidence of a potential benefit
from cognitive rehabilitation including the use of
mnemonics association strategies and computer-
assisted training programs4142 A recent systematic
review of the literature on cognitive rehabilitation
programs for persons with mild cognitive impair-
ment including some data from randomized clin-
ical trials showed signif icant improvement in
cognitive function at the end of training42
Observational data have shown associations
between the presence of cardiovascular risk factors
in patients with mild cognitive impairment and an
increased risk of progression to dementia7 Such
risk factors should be addressed although there
is no definitive evidence that modif ication of risk
factors slows disease progression In a randomized
trial that used the Cognitive Subscale of the Alz-
heimerrsquos Disease Assessment Scale to compare the
effect of a physical exercise program (brisk walking
for 150 minutes per week) with that of usual care
and education in persons with subjective memory
loss the exercise group had better cognitive func-
tion at 6 months (the primary study outcome) with
some residual benefit noted at 18 months43
Ar eas o f Un cer t ai n t y
More data are needed regarding the usefulness of
various potential predictors of progression to de-
mentia and their role in clinical practice Further
data on these concerns are awaited from the Alz-
heimerrsquos Disease Neuroimaging Initiative under
way in the United States and Canada2744 and from
similar ongoing studies in Japan Europe and Aus-
tralia Some of the goals of these studies are to
better understand the role of MRI f indings (eg
hippocampal atrophy)2245 f indings on 18FDG-PET
(patterns of hypometabolism in the brain) cere-
brospinal f luid markers (levels of Aβ42 and tau)
and f indings on molecular imaging (amyloid
plaques in the brain) in identifying the subgroup
of persons with amnestic mild cognitive impair-
ment who are likely to undergo progression to
clinical Alz hei merrsquos disease274647 Major challeng-
es are to determine optimal cutoff points for these
tests and to compare their relative reliability (alone
and in combination) Randomized trials are need-
ed to assess the potential benefits of pharmaco-
logic and lifestyle interventions in persons with
mild cognitive impairment who are predicted to
be at high risk for rapid progression to Alzheimerrsquos
A B C
Figure 3 Axial Scans of the Brain Obtained with Positron-Emission Tomography and the Use of Amyloid-Binding
Carbon 11ndashLabeled Pittsburgh Compound B
The yellow and red areas indicate retention of the amyloid-binding tracer reflecting amyloid deposits The patient
with normal cognition (Panel A) has no tracer retention whereas the patient with amnestic mild cognitive impair-
ment has an intermediate amount of tracer retention (Panel B) and the patient with Alzheimerrsquos disease has promi-
nent tracer retention (Panel C)
The New England Journal of Medicine
Downloaded from nejmorg at UECE on July 24 2016 For personal use only No other uses without permission
Copyright copy 2011 Massachusetts Medical Society All rights reserved
Outros Marcadores
bull Liacutequor
bull Dosagem de TAU (decaacuteda de 90)
bull Dosagem de AB-42
bull Growdon 1999 (AB-42 e TAU na DA)
Mattsson N et al 2009 JAMA
bull 750 pacientes com Comprometimento Cognitivo Leve
bull Seguimento por 2 anos
bull 271 evoluiram para DA
bull 59 apresentaram outras demecircncias
bull Baixos niacuteveis de Aβ-42 e altos de Fosfo-Tau com maior
acuraacutecia para evoluccedilatildeo para DA
bull 74 pacientes com Doenccedila de Alzheimer x 142 com
Comprometimento Cognitivo Leve e 82 controles
bull Hipometabolismo
- Precuneos
- Ciacutengulo Posterior
- Coacutertex Temporo-parietal
- Coacutertex Frontal
Koivunen et al Neurology 2011
bull 29 pacientes acompanhados por 2 anos
bull Avaliaccedilatildeo de PET com PIB e RM (Atrofia de
hipocampo)
bull 1729 converteram
bull Maior depoacutesito de PIB Ciacutengulo Posterior frontal lateral
temporal e putamem com maior atrofia
bull Pouca modificaccedilao no PIB em 2 anos
bull Aumento da atrofia
Hipoacutetese da Evoluccedilatildeo Temporal
dos processos fisiopatoloacutegicos
Biomarcador e CCL
Criteacuterios para Pesquisa DA
Porque utilizar biomarcador empacientes com quadros cognitivos
bull O paciente vai piorar dos sintomas cognitivos
bull Existe um processo patoloacutegico jaacute conhecido
bull Existe dano neuronal Topografia
bull Falsos positivos o que fazer
Ressonacircncia Magneacutetica de Cracircnio
bull Atrofia hipocampal
bull Casos leves ou assintomaacuteticos
bull Avaliaccedilatildeo de espessura cortical (Walhovd K et al 2010)
bull DTI (Sexton C et al 2011)
Ressonacircncia Magneacutetica
Vantagens
bull Disponibilidade
bull Visualizaccedilatildeo de atrofia
bull Possibilidade de vaacuterias mediccedilotildees
Limitaccedilotildees
bull Teacutecnicas habituaispoucos sensiacuteveis paraquadros leves
bull Reflete somente o danoneuronal
bull Teacutecnicas especiaispouca disponibilidade
Caso
bull RM laudo normal
PET-FDG
Vantagens
bull Sensibilidade
bull Reflete dano neuronal
Limitaccedilotildees
bull Custo
bull Sem ponto de corte
bull Natildeo especiacutefico do dano patoloacutegico
Caso
bull PET-FDG hipometabolismo FTP esquerdo e leve a Direita frontal e parietal
bull O que esse laudo mostra
bull Que eu consegui examinar e topografar direito
PET Amiloide
bull Dificuldades Iniciais
bull Marcador a base de Fluor
PET Tau and Amyloid-β Burden in Mild Alzheimers Disease Divergent Relationshipwith Age Cognition and Cerebrospinal Fluid BiomarkersKoychev I1 Gunn RN23 Firouzian A2 Lawson J1 Zamboni G1 Ridha B4 Sahakian BJ5 Rowe JB6 Thomas A7 Rochester L7 Ffytche D8 Howard R9 Zetterberg H9101112 MacKay C1 Lovestone S1 Deep and Frequent Phenotyping study team
J Alzheimers Dis 2017 Aug 8
PET Marcador Amiloacuteide
Vantagens
bull Refletem o processo patoloacutegico
bull Conseguem detectar indiviacuteduos assintomaacuteticos em risco
bull Predizem piora cliacutenica
Limitaccedilotildees
bull Custo
bull Disponibilidade
bull Normalizaccedilatildeo de pontos de corte
Caso
bull PET-Amiloacuteide
241 Estudos
11341 Pacientes
7086 Pacientes
Entatildeo vamos coletar Liacutequor para todos
Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory ClinicPatients in a Prospective CohortHandels RL12 Joore MA23 Vos SJ1 Aalten P1 Ramakers IH1 Rikkert MO4 Scheltens P5 Jansen WJ1 Visser PJ15 van Berckel BM5 van Domburg P6 Smid M7 Hoff E8 Hoogmoed J910 Bouwman F5 Claassen J4 Leentjens AF1 Wolfs CA1 Severens JL11 Verhey FR1Author information
bull 200 DA
bull 16 DA prodromica
bull 69 DFT
bull 59 DCB
bull 16 PSP
bull 44 DCL
bull 22 ACP
bull 41 Demecircncia Semacircntica
bull 52 Afasias logopecircnicas
bull 11 Afasias natildeo fluentes
bull 71 Depressatildeo
bull 49 Queixa subjetiva de memoacuteria
bull DA -100
bull DA prodromica-100
bull 439 dos outros pacientes tbpositivos
bull 818 ACP
bull 788 Afasia logopecircnica
bull 50 DCL
bull 458 DCB
bull 454 afasias natildeo fluentes
bull 366 demecircncia semacircnticas
bull 145 das DFT
bull 117 (Depressatildeo e QSM)
E o teste de Memoacuteria
bull Sensibilidade100
bull Especificidade de 748
bull Intrusotildees Sensibilidade de 83 e Especificidade72
bull 273 tinham deacuteficit hipocampal
bull 366 dos deprimidos
bull 40 DCL
bull 375 PSP
bull 319 DFT
bull 273 Afasia natildeo fluente
bull 227 ACP
bull 22 Demecircncia Semacircntica
bull 22 DCB
bull 58 Afasia logopecircnica
Existiu uma correlaccedilatildeo desempenho com os marcadores
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
Caso Cliacutenico
bull HPP cesariana depressatildeo
bull Med Desvenlafaxina 50mg Zolpiden 10mg
bull Haacutebitos etilismo leve
bull Alergia ndn
bull Hist Familiar Matildee com quadro demencial aos 62 anos
Avaliaccedilatildeo Cognitivabull ACE76100
atenccedilatildeo OT5 OE5 MI3 AC93-x-x-72-x=1518Memoacuteria1+6+4+6+5=2226FP peru pato pinto passaro preacutedio parque pneu=7FA galinha peru pato baleia cachorro gato peixe camaratildeo rato tartaruga passaros cavalo leatildeo=13(3+4=714)LIng1+3+1+2+1+1+10+2+1=2226V-E0+0+4+3+3=1016
Exame Neuroloacutegico
bull Equiliacutebrio movimentos em matildeo D e flexatildeoFM elevaccedilatildeo de MSD (levitaccedilatildeo e fica fazendo movimentos em MID)Reflexos Vivos
bull Apraxia evidente pior a DCoordenaccedilatildeo index nariz normal e leve disdiadococinesiaSensib Discreta anartestesia em MIDNC sem alteraccedilotildees
Hipoacutetese Diagnoacutestica
bull Degeneraccedilatildeo Cortico-Basal
bull Doenccedila de Alzheimer atiacutepica
E agora
Exames Complementares nas Demecircncias
bull Descartar causas secundaacuterias
bull Padrotildees especiacuteficos de atrofia
Nova Visatildeo
bull Diferenciaccedilatildeo dos tipos de demecircncia
bull Diagnoacutestico precoce
bull Marcador de evoluccedilatildeo
bull Resposta terapecircutica
Ressonacircncia Magneacuteticabull Natildeo deve ser mais utilizado como somente para
excluir causas secundaacuterias
bull Eacute um biomarcador de dano neuronal
bull Avaliar com cuidado atrofias assimeacutetricas
The n ew en g l an d j o u r n a l of med i c i n e
n engl j med 36423 nejmor g june 9 20112230
A Swedish study showed that subjects with mild
cognitive impairment who had low levels of
β-amyloid peptide 42 (Aβ42) and elevated levels
of tau protein in cerebrospinal f luid were sig-
nif icantly more likely to undergo progression to
Alzheimerrsquos disease than subjects without this
prof ile (hazard ratio 177 95 conf idence inter-
val 53 to 589) a similar relative risk of progres-
sion was associated with a low ratio of Aβ42 to
tau in the cerebrospinal f luid28 An international
multicenter study of 750 subjects with mild cogni-
tive impairment corroborated these general f ind-
ings2930 but used different cutoff points for ab-
normal f indings The reliability of these markers
is highly variable across laboratories standard-
ization will be needed before they are considered
for incorporation into routine care
The use of molecular imaging particularly of
amyloid plaques in the brain (Fig 3) has also been
studied as a possible approach to risk stratif ica-
tion31-33 In several studies subjects with mild cog-
nitive impairment in whom amyloid was detected
on positron-emission tomography (PET) with the
use of the amyloid-binding carbon 11ndashlabeled Pitts-
burgh compound B had more rapid progression to
Alzheimerrsquos disease than did subjects in whom
amyloid was not detected34 The rationale for using
this technique to predict disease progression is that
the presence of amyloid in a patient with mild
cognitive impairment is likely to indicate that the
patient has early Alzheimerrsquos disease however
amyloid has been detected on autopsy in clinical-
ly normal persons indicating that the predictive
value of this measure requires further study35
Management
From a clinical perspective patients with mild cog-
nitive impairment should not be labeled as having
early Alzheimerrsquos disease prodromal Alzheimerrsquos
disease or mild cognitive impairment of the Alz-
heimerrsquos disease type since the patient and fam-
ily are likely to hear only ―Alzheimerrsquos disease and
not appreciate the uncertainty of the association
with Alzheimerrsquos disease36 Clinicians should make
it clear that mild cognitive impairment is an abnor-
mal condition but that the precise outcome is not
certain
At present no medication intended for the
treatment of mild cognitive impairment has been
approved by the Food and Drug Administration
(FDA) In several placebo-controlled clinical trials
there was no signif icant reduction in rates of
progression to dementia among patients with
mild cognitive impairment who were treated with
agents used to treat Alzheimerrsquos disease (donepe-
zil galantamine and rivastigmine administered
at standard doses for Alzheimerrsquos disease for 2 to
4 years)537-40 In one trial evaluating the effects of
high-dose vitamin E (2000 IU daily) or donepezil
in persons with mild cognitive impairment do-
nep ezil signif icantly reduced the risk of pro-
gression to Alzheimerrsquos disease for the f irst 12
months of the study (and for up to 24 months in
the subgroup of subjects who were carriers of
APOE ε4) but had no signif icant effect on the
risk of Alz heimerrsquos disease at 36 months which
was the primary study outcome vitamin E did
not signif icantly reduce the risk of progression
at any time point assessed5
A B C
Figure 2 Coronal MRI Scans from Patients with Normal Cognition Mild Cognitive Impairment and Alzheimerrsquos
Disease
The arrows depict the hippocampal formations and the progressive atrophy characterizing the progression from nor-
mal cognition (Panel A) to mild cognitive impairment (Panel B) to Alzheimerrsquos disease (Panel C)
The New England Journal of Medicine
Downloaded from nejmorg at UECE on July 24 2016 For personal use only No other uses without permission
Copyright copy 2011 Massachusetts Medical Society All rights reserved
cl i n i cal pr act i ce
n engl j med 36423 nejmor g june 9 2011 2231
One potential explanation for the apparent lack
of eff icacy in the clinical trials of interventions in
persons with mild cognitive impairment mdash other
than a true absence of drug eff icacy mdash concerns
the heterogeneity of the subjects As the diagnos-
tic threshold moves to an earlier point in the clini-
cal spectrum of cognitive impairment the subtle
changes in cognition could be due to a variety of
causes other than a degenerative brain disease
making it diff icult to determine whether an inter-
vention has had a signif icant effect
There is some evidence of a potential benefit
from cognitive rehabilitation including the use of
mnemonics association strategies and computer-
assisted training programs4142 A recent systematic
review of the literature on cognitive rehabilitation
programs for persons with mild cognitive impair-
ment including some data from randomized clin-
ical trials showed signif icant improvement in
cognitive function at the end of training42
Observational data have shown associations
between the presence of cardiovascular risk factors
in patients with mild cognitive impairment and an
increased risk of progression to dementia7 Such
risk factors should be addressed although there
is no definitive evidence that modif ication of risk
factors slows disease progression In a randomized
trial that used the Cognitive Subscale of the Alz-
heimerrsquos Disease Assessment Scale to compare the
effect of a physical exercise program (brisk walking
for 150 minutes per week) with that of usual care
and education in persons with subjective memory
loss the exercise group had better cognitive func-
tion at 6 months (the primary study outcome) with
some residual benefit noted at 18 months43
Ar eas o f Un cer t ai n t y
More data are needed regarding the usefulness of
various potential predictors of progression to de-
mentia and their role in clinical practice Further
data on these concerns are awaited from the Alz-
heimerrsquos Disease Neuroimaging Initiative under
way in the United States and Canada2744 and from
similar ongoing studies in Japan Europe and Aus-
tralia Some of the goals of these studies are to
better understand the role of MRI f indings (eg
hippocampal atrophy)2245 f indings on 18FDG-PET
(patterns of hypometabolism in the brain) cere-
brospinal f luid markers (levels of Aβ42 and tau)
and f indings on molecular imaging (amyloid
plaques in the brain) in identifying the subgroup
of persons with amnestic mild cognitive impair-
ment who are likely to undergo progression to
clinical Alz hei merrsquos disease274647 Major challeng-
es are to determine optimal cutoff points for these
tests and to compare their relative reliability (alone
and in combination) Randomized trials are need-
ed to assess the potential benefits of pharmaco-
logic and lifestyle interventions in persons with
mild cognitive impairment who are predicted to
be at high risk for rapid progression to Alzheimerrsquos
A B C
Figure 3 Axial Scans of the Brain Obtained with Positron-Emission Tomography and the Use of Amyloid-Binding
Carbon 11ndashLabeled Pittsburgh Compound B
The yellow and red areas indicate retention of the amyloid-binding tracer reflecting amyloid deposits The patient
with normal cognition (Panel A) has no tracer retention whereas the patient with amnestic mild cognitive impair-
ment has an intermediate amount of tracer retention (Panel B) and the patient with Alzheimerrsquos disease has promi-
nent tracer retention (Panel C)
The New England Journal of Medicine
Downloaded from nejmorg at UECE on July 24 2016 For personal use only No other uses without permission
Copyright copy 2011 Massachusetts Medical Society All rights reserved
Outros Marcadores
bull Liacutequor
bull Dosagem de TAU (decaacuteda de 90)
bull Dosagem de AB-42
bull Growdon 1999 (AB-42 e TAU na DA)
Mattsson N et al 2009 JAMA
bull 750 pacientes com Comprometimento Cognitivo Leve
bull Seguimento por 2 anos
bull 271 evoluiram para DA
bull 59 apresentaram outras demecircncias
bull Baixos niacuteveis de Aβ-42 e altos de Fosfo-Tau com maior
acuraacutecia para evoluccedilatildeo para DA
bull 74 pacientes com Doenccedila de Alzheimer x 142 com
Comprometimento Cognitivo Leve e 82 controles
bull Hipometabolismo
- Precuneos
- Ciacutengulo Posterior
- Coacutertex Temporo-parietal
- Coacutertex Frontal
Koivunen et al Neurology 2011
bull 29 pacientes acompanhados por 2 anos
bull Avaliaccedilatildeo de PET com PIB e RM (Atrofia de
hipocampo)
bull 1729 converteram
bull Maior depoacutesito de PIB Ciacutengulo Posterior frontal lateral
temporal e putamem com maior atrofia
bull Pouca modificaccedilao no PIB em 2 anos
bull Aumento da atrofia
Hipoacutetese da Evoluccedilatildeo Temporal
dos processos fisiopatoloacutegicos
Biomarcador e CCL
Criteacuterios para Pesquisa DA
Porque utilizar biomarcador empacientes com quadros cognitivos
bull O paciente vai piorar dos sintomas cognitivos
bull Existe um processo patoloacutegico jaacute conhecido
bull Existe dano neuronal Topografia
bull Falsos positivos o que fazer
Ressonacircncia Magneacutetica de Cracircnio
bull Atrofia hipocampal
bull Casos leves ou assintomaacuteticos
bull Avaliaccedilatildeo de espessura cortical (Walhovd K et al 2010)
bull DTI (Sexton C et al 2011)
Ressonacircncia Magneacutetica
Vantagens
bull Disponibilidade
bull Visualizaccedilatildeo de atrofia
bull Possibilidade de vaacuterias mediccedilotildees
Limitaccedilotildees
bull Teacutecnicas habituaispoucos sensiacuteveis paraquadros leves
bull Reflete somente o danoneuronal
bull Teacutecnicas especiaispouca disponibilidade
Caso
bull RM laudo normal
PET-FDG
Vantagens
bull Sensibilidade
bull Reflete dano neuronal
Limitaccedilotildees
bull Custo
bull Sem ponto de corte
bull Natildeo especiacutefico do dano patoloacutegico
Caso
bull PET-FDG hipometabolismo FTP esquerdo e leve a Direita frontal e parietal
bull O que esse laudo mostra
bull Que eu consegui examinar e topografar direito
PET Amiloide
bull Dificuldades Iniciais
bull Marcador a base de Fluor
PET Tau and Amyloid-β Burden in Mild Alzheimers Disease Divergent Relationshipwith Age Cognition and Cerebrospinal Fluid BiomarkersKoychev I1 Gunn RN23 Firouzian A2 Lawson J1 Zamboni G1 Ridha B4 Sahakian BJ5 Rowe JB6 Thomas A7 Rochester L7 Ffytche D8 Howard R9 Zetterberg H9101112 MacKay C1 Lovestone S1 Deep and Frequent Phenotyping study team
J Alzheimers Dis 2017 Aug 8
PET Marcador Amiloacuteide
Vantagens
bull Refletem o processo patoloacutegico
bull Conseguem detectar indiviacuteduos assintomaacuteticos em risco
bull Predizem piora cliacutenica
Limitaccedilotildees
bull Custo
bull Disponibilidade
bull Normalizaccedilatildeo de pontos de corte
Caso
bull PET-Amiloacuteide
241 Estudos
11341 Pacientes
7086 Pacientes
Entatildeo vamos coletar Liacutequor para todos
Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory ClinicPatients in a Prospective CohortHandels RL12 Joore MA23 Vos SJ1 Aalten P1 Ramakers IH1 Rikkert MO4 Scheltens P5 Jansen WJ1 Visser PJ15 van Berckel BM5 van Domburg P6 Smid M7 Hoff E8 Hoogmoed J910 Bouwman F5 Claassen J4 Leentjens AF1 Wolfs CA1 Severens JL11 Verhey FR1Author information
bull 200 DA
bull 16 DA prodromica
bull 69 DFT
bull 59 DCB
bull 16 PSP
bull 44 DCL
bull 22 ACP
bull 41 Demecircncia Semacircntica
bull 52 Afasias logopecircnicas
bull 11 Afasias natildeo fluentes
bull 71 Depressatildeo
bull 49 Queixa subjetiva de memoacuteria
bull DA -100
bull DA prodromica-100
bull 439 dos outros pacientes tbpositivos
bull 818 ACP
bull 788 Afasia logopecircnica
bull 50 DCL
bull 458 DCB
bull 454 afasias natildeo fluentes
bull 366 demecircncia semacircnticas
bull 145 das DFT
bull 117 (Depressatildeo e QSM)
E o teste de Memoacuteria
bull Sensibilidade100
bull Especificidade de 748
bull Intrusotildees Sensibilidade de 83 e Especificidade72
bull 273 tinham deacuteficit hipocampal
bull 366 dos deprimidos
bull 40 DCL
bull 375 PSP
bull 319 DFT
bull 273 Afasia natildeo fluente
bull 227 ACP
bull 22 Demecircncia Semacircntica
bull 22 DCB
bull 58 Afasia logopecircnica
Existiu uma correlaccedilatildeo desempenho com os marcadores
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
Avaliaccedilatildeo Cognitivabull ACE76100
atenccedilatildeo OT5 OE5 MI3 AC93-x-x-72-x=1518Memoacuteria1+6+4+6+5=2226FP peru pato pinto passaro preacutedio parque pneu=7FA galinha peru pato baleia cachorro gato peixe camaratildeo rato tartaruga passaros cavalo leatildeo=13(3+4=714)LIng1+3+1+2+1+1+10+2+1=2226V-E0+0+4+3+3=1016
Exame Neuroloacutegico
bull Equiliacutebrio movimentos em matildeo D e flexatildeoFM elevaccedilatildeo de MSD (levitaccedilatildeo e fica fazendo movimentos em MID)Reflexos Vivos
bull Apraxia evidente pior a DCoordenaccedilatildeo index nariz normal e leve disdiadococinesiaSensib Discreta anartestesia em MIDNC sem alteraccedilotildees
Hipoacutetese Diagnoacutestica
bull Degeneraccedilatildeo Cortico-Basal
bull Doenccedila de Alzheimer atiacutepica
E agora
Exames Complementares nas Demecircncias
bull Descartar causas secundaacuterias
bull Padrotildees especiacuteficos de atrofia
Nova Visatildeo
bull Diferenciaccedilatildeo dos tipos de demecircncia
bull Diagnoacutestico precoce
bull Marcador de evoluccedilatildeo
bull Resposta terapecircutica
Ressonacircncia Magneacuteticabull Natildeo deve ser mais utilizado como somente para
excluir causas secundaacuterias
bull Eacute um biomarcador de dano neuronal
bull Avaliar com cuidado atrofias assimeacutetricas
The n ew en g l an d j o u r n a l of med i c i n e
n engl j med 36423 nejmor g june 9 20112230
A Swedish study showed that subjects with mild
cognitive impairment who had low levels of
β-amyloid peptide 42 (Aβ42) and elevated levels
of tau protein in cerebrospinal f luid were sig-
nif icantly more likely to undergo progression to
Alzheimerrsquos disease than subjects without this
prof ile (hazard ratio 177 95 conf idence inter-
val 53 to 589) a similar relative risk of progres-
sion was associated with a low ratio of Aβ42 to
tau in the cerebrospinal f luid28 An international
multicenter study of 750 subjects with mild cogni-
tive impairment corroborated these general f ind-
ings2930 but used different cutoff points for ab-
normal f indings The reliability of these markers
is highly variable across laboratories standard-
ization will be needed before they are considered
for incorporation into routine care
The use of molecular imaging particularly of
amyloid plaques in the brain (Fig 3) has also been
studied as a possible approach to risk stratif ica-
tion31-33 In several studies subjects with mild cog-
nitive impairment in whom amyloid was detected
on positron-emission tomography (PET) with the
use of the amyloid-binding carbon 11ndashlabeled Pitts-
burgh compound B had more rapid progression to
Alzheimerrsquos disease than did subjects in whom
amyloid was not detected34 The rationale for using
this technique to predict disease progression is that
the presence of amyloid in a patient with mild
cognitive impairment is likely to indicate that the
patient has early Alzheimerrsquos disease however
amyloid has been detected on autopsy in clinical-
ly normal persons indicating that the predictive
value of this measure requires further study35
Management
From a clinical perspective patients with mild cog-
nitive impairment should not be labeled as having
early Alzheimerrsquos disease prodromal Alzheimerrsquos
disease or mild cognitive impairment of the Alz-
heimerrsquos disease type since the patient and fam-
ily are likely to hear only ―Alzheimerrsquos disease and
not appreciate the uncertainty of the association
with Alzheimerrsquos disease36 Clinicians should make
it clear that mild cognitive impairment is an abnor-
mal condition but that the precise outcome is not
certain
At present no medication intended for the
treatment of mild cognitive impairment has been
approved by the Food and Drug Administration
(FDA) In several placebo-controlled clinical trials
there was no signif icant reduction in rates of
progression to dementia among patients with
mild cognitive impairment who were treated with
agents used to treat Alzheimerrsquos disease (donepe-
zil galantamine and rivastigmine administered
at standard doses for Alzheimerrsquos disease for 2 to
4 years)537-40 In one trial evaluating the effects of
high-dose vitamin E (2000 IU daily) or donepezil
in persons with mild cognitive impairment do-
nep ezil signif icantly reduced the risk of pro-
gression to Alzheimerrsquos disease for the f irst 12
months of the study (and for up to 24 months in
the subgroup of subjects who were carriers of
APOE ε4) but had no signif icant effect on the
risk of Alz heimerrsquos disease at 36 months which
was the primary study outcome vitamin E did
not signif icantly reduce the risk of progression
at any time point assessed5
A B C
Figure 2 Coronal MRI Scans from Patients with Normal Cognition Mild Cognitive Impairment and Alzheimerrsquos
Disease
The arrows depict the hippocampal formations and the progressive atrophy characterizing the progression from nor-
mal cognition (Panel A) to mild cognitive impairment (Panel B) to Alzheimerrsquos disease (Panel C)
The New England Journal of Medicine
Downloaded from nejmorg at UECE on July 24 2016 For personal use only No other uses without permission
Copyright copy 2011 Massachusetts Medical Society All rights reserved
cl i n i cal pr act i ce
n engl j med 36423 nejmor g june 9 2011 2231
One potential explanation for the apparent lack
of eff icacy in the clinical trials of interventions in
persons with mild cognitive impairment mdash other
than a true absence of drug eff icacy mdash concerns
the heterogeneity of the subjects As the diagnos-
tic threshold moves to an earlier point in the clini-
cal spectrum of cognitive impairment the subtle
changes in cognition could be due to a variety of
causes other than a degenerative brain disease
making it diff icult to determine whether an inter-
vention has had a signif icant effect
There is some evidence of a potential benefit
from cognitive rehabilitation including the use of
mnemonics association strategies and computer-
assisted training programs4142 A recent systematic
review of the literature on cognitive rehabilitation
programs for persons with mild cognitive impair-
ment including some data from randomized clin-
ical trials showed signif icant improvement in
cognitive function at the end of training42
Observational data have shown associations
between the presence of cardiovascular risk factors
in patients with mild cognitive impairment and an
increased risk of progression to dementia7 Such
risk factors should be addressed although there
is no definitive evidence that modif ication of risk
factors slows disease progression In a randomized
trial that used the Cognitive Subscale of the Alz-
heimerrsquos Disease Assessment Scale to compare the
effect of a physical exercise program (brisk walking
for 150 minutes per week) with that of usual care
and education in persons with subjective memory
loss the exercise group had better cognitive func-
tion at 6 months (the primary study outcome) with
some residual benefit noted at 18 months43
Ar eas o f Un cer t ai n t y
More data are needed regarding the usefulness of
various potential predictors of progression to de-
mentia and their role in clinical practice Further
data on these concerns are awaited from the Alz-
heimerrsquos Disease Neuroimaging Initiative under
way in the United States and Canada2744 and from
similar ongoing studies in Japan Europe and Aus-
tralia Some of the goals of these studies are to
better understand the role of MRI f indings (eg
hippocampal atrophy)2245 f indings on 18FDG-PET
(patterns of hypometabolism in the brain) cere-
brospinal f luid markers (levels of Aβ42 and tau)
and f indings on molecular imaging (amyloid
plaques in the brain) in identifying the subgroup
of persons with amnestic mild cognitive impair-
ment who are likely to undergo progression to
clinical Alz hei merrsquos disease274647 Major challeng-
es are to determine optimal cutoff points for these
tests and to compare their relative reliability (alone
and in combination) Randomized trials are need-
ed to assess the potential benefits of pharmaco-
logic and lifestyle interventions in persons with
mild cognitive impairment who are predicted to
be at high risk for rapid progression to Alzheimerrsquos
A B C
Figure 3 Axial Scans of the Brain Obtained with Positron-Emission Tomography and the Use of Amyloid-Binding
Carbon 11ndashLabeled Pittsburgh Compound B
The yellow and red areas indicate retention of the amyloid-binding tracer reflecting amyloid deposits The patient
with normal cognition (Panel A) has no tracer retention whereas the patient with amnestic mild cognitive impair-
ment has an intermediate amount of tracer retention (Panel B) and the patient with Alzheimerrsquos disease has promi-
nent tracer retention (Panel C)
The New England Journal of Medicine
Downloaded from nejmorg at UECE on July 24 2016 For personal use only No other uses without permission
Copyright copy 2011 Massachusetts Medical Society All rights reserved
Outros Marcadores
bull Liacutequor
bull Dosagem de TAU (decaacuteda de 90)
bull Dosagem de AB-42
bull Growdon 1999 (AB-42 e TAU na DA)
Mattsson N et al 2009 JAMA
bull 750 pacientes com Comprometimento Cognitivo Leve
bull Seguimento por 2 anos
bull 271 evoluiram para DA
bull 59 apresentaram outras demecircncias
bull Baixos niacuteveis de Aβ-42 e altos de Fosfo-Tau com maior
acuraacutecia para evoluccedilatildeo para DA
bull 74 pacientes com Doenccedila de Alzheimer x 142 com
Comprometimento Cognitivo Leve e 82 controles
bull Hipometabolismo
- Precuneos
- Ciacutengulo Posterior
- Coacutertex Temporo-parietal
- Coacutertex Frontal
Koivunen et al Neurology 2011
bull 29 pacientes acompanhados por 2 anos
bull Avaliaccedilatildeo de PET com PIB e RM (Atrofia de
hipocampo)
bull 1729 converteram
bull Maior depoacutesito de PIB Ciacutengulo Posterior frontal lateral
temporal e putamem com maior atrofia
bull Pouca modificaccedilao no PIB em 2 anos
bull Aumento da atrofia
Hipoacutetese da Evoluccedilatildeo Temporal
dos processos fisiopatoloacutegicos
Biomarcador e CCL
Criteacuterios para Pesquisa DA
Porque utilizar biomarcador empacientes com quadros cognitivos
bull O paciente vai piorar dos sintomas cognitivos
bull Existe um processo patoloacutegico jaacute conhecido
bull Existe dano neuronal Topografia
bull Falsos positivos o que fazer
Ressonacircncia Magneacutetica de Cracircnio
bull Atrofia hipocampal
bull Casos leves ou assintomaacuteticos
bull Avaliaccedilatildeo de espessura cortical (Walhovd K et al 2010)
bull DTI (Sexton C et al 2011)
Ressonacircncia Magneacutetica
Vantagens
bull Disponibilidade
bull Visualizaccedilatildeo de atrofia
bull Possibilidade de vaacuterias mediccedilotildees
Limitaccedilotildees
bull Teacutecnicas habituaispoucos sensiacuteveis paraquadros leves
bull Reflete somente o danoneuronal
bull Teacutecnicas especiaispouca disponibilidade
Caso
bull RM laudo normal
PET-FDG
Vantagens
bull Sensibilidade
bull Reflete dano neuronal
Limitaccedilotildees
bull Custo
bull Sem ponto de corte
bull Natildeo especiacutefico do dano patoloacutegico
Caso
bull PET-FDG hipometabolismo FTP esquerdo e leve a Direita frontal e parietal
bull O que esse laudo mostra
bull Que eu consegui examinar e topografar direito
PET Amiloide
bull Dificuldades Iniciais
bull Marcador a base de Fluor
PET Tau and Amyloid-β Burden in Mild Alzheimers Disease Divergent Relationshipwith Age Cognition and Cerebrospinal Fluid BiomarkersKoychev I1 Gunn RN23 Firouzian A2 Lawson J1 Zamboni G1 Ridha B4 Sahakian BJ5 Rowe JB6 Thomas A7 Rochester L7 Ffytche D8 Howard R9 Zetterberg H9101112 MacKay C1 Lovestone S1 Deep and Frequent Phenotyping study team
J Alzheimers Dis 2017 Aug 8
PET Marcador Amiloacuteide
Vantagens
bull Refletem o processo patoloacutegico
bull Conseguem detectar indiviacuteduos assintomaacuteticos em risco
bull Predizem piora cliacutenica
Limitaccedilotildees
bull Custo
bull Disponibilidade
bull Normalizaccedilatildeo de pontos de corte
Caso
bull PET-Amiloacuteide
241 Estudos
11341 Pacientes
7086 Pacientes
Entatildeo vamos coletar Liacutequor para todos
Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory ClinicPatients in a Prospective CohortHandels RL12 Joore MA23 Vos SJ1 Aalten P1 Ramakers IH1 Rikkert MO4 Scheltens P5 Jansen WJ1 Visser PJ15 van Berckel BM5 van Domburg P6 Smid M7 Hoff E8 Hoogmoed J910 Bouwman F5 Claassen J4 Leentjens AF1 Wolfs CA1 Severens JL11 Verhey FR1Author information
bull 200 DA
bull 16 DA prodromica
bull 69 DFT
bull 59 DCB
bull 16 PSP
bull 44 DCL
bull 22 ACP
bull 41 Demecircncia Semacircntica
bull 52 Afasias logopecircnicas
bull 11 Afasias natildeo fluentes
bull 71 Depressatildeo
bull 49 Queixa subjetiva de memoacuteria
bull DA -100
bull DA prodromica-100
bull 439 dos outros pacientes tbpositivos
bull 818 ACP
bull 788 Afasia logopecircnica
bull 50 DCL
bull 458 DCB
bull 454 afasias natildeo fluentes
bull 366 demecircncia semacircnticas
bull 145 das DFT
bull 117 (Depressatildeo e QSM)
E o teste de Memoacuteria
bull Sensibilidade100
bull Especificidade de 748
bull Intrusotildees Sensibilidade de 83 e Especificidade72
bull 273 tinham deacuteficit hipocampal
bull 366 dos deprimidos
bull 40 DCL
bull 375 PSP
bull 319 DFT
bull 273 Afasia natildeo fluente
bull 227 ACP
bull 22 Demecircncia Semacircntica
bull 22 DCB
bull 58 Afasia logopecircnica
Existiu uma correlaccedilatildeo desempenho com os marcadores
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
Exame Neuroloacutegico
bull Equiliacutebrio movimentos em matildeo D e flexatildeoFM elevaccedilatildeo de MSD (levitaccedilatildeo e fica fazendo movimentos em MID)Reflexos Vivos
bull Apraxia evidente pior a DCoordenaccedilatildeo index nariz normal e leve disdiadococinesiaSensib Discreta anartestesia em MIDNC sem alteraccedilotildees
Hipoacutetese Diagnoacutestica
bull Degeneraccedilatildeo Cortico-Basal
bull Doenccedila de Alzheimer atiacutepica
E agora
Exames Complementares nas Demecircncias
bull Descartar causas secundaacuterias
bull Padrotildees especiacuteficos de atrofia
Nova Visatildeo
bull Diferenciaccedilatildeo dos tipos de demecircncia
bull Diagnoacutestico precoce
bull Marcador de evoluccedilatildeo
bull Resposta terapecircutica
Ressonacircncia Magneacuteticabull Natildeo deve ser mais utilizado como somente para
excluir causas secundaacuterias
bull Eacute um biomarcador de dano neuronal
bull Avaliar com cuidado atrofias assimeacutetricas
The n ew en g l an d j o u r n a l of med i c i n e
n engl j med 36423 nejmor g june 9 20112230
A Swedish study showed that subjects with mild
cognitive impairment who had low levels of
β-amyloid peptide 42 (Aβ42) and elevated levels
of tau protein in cerebrospinal f luid were sig-
nif icantly more likely to undergo progression to
Alzheimerrsquos disease than subjects without this
prof ile (hazard ratio 177 95 conf idence inter-
val 53 to 589) a similar relative risk of progres-
sion was associated with a low ratio of Aβ42 to
tau in the cerebrospinal f luid28 An international
multicenter study of 750 subjects with mild cogni-
tive impairment corroborated these general f ind-
ings2930 but used different cutoff points for ab-
normal f indings The reliability of these markers
is highly variable across laboratories standard-
ization will be needed before they are considered
for incorporation into routine care
The use of molecular imaging particularly of
amyloid plaques in the brain (Fig 3) has also been
studied as a possible approach to risk stratif ica-
tion31-33 In several studies subjects with mild cog-
nitive impairment in whom amyloid was detected
on positron-emission tomography (PET) with the
use of the amyloid-binding carbon 11ndashlabeled Pitts-
burgh compound B had more rapid progression to
Alzheimerrsquos disease than did subjects in whom
amyloid was not detected34 The rationale for using
this technique to predict disease progression is that
the presence of amyloid in a patient with mild
cognitive impairment is likely to indicate that the
patient has early Alzheimerrsquos disease however
amyloid has been detected on autopsy in clinical-
ly normal persons indicating that the predictive
value of this measure requires further study35
Management
From a clinical perspective patients with mild cog-
nitive impairment should not be labeled as having
early Alzheimerrsquos disease prodromal Alzheimerrsquos
disease or mild cognitive impairment of the Alz-
heimerrsquos disease type since the patient and fam-
ily are likely to hear only ―Alzheimerrsquos disease and
not appreciate the uncertainty of the association
with Alzheimerrsquos disease36 Clinicians should make
it clear that mild cognitive impairment is an abnor-
mal condition but that the precise outcome is not
certain
At present no medication intended for the
treatment of mild cognitive impairment has been
approved by the Food and Drug Administration
(FDA) In several placebo-controlled clinical trials
there was no signif icant reduction in rates of
progression to dementia among patients with
mild cognitive impairment who were treated with
agents used to treat Alzheimerrsquos disease (donepe-
zil galantamine and rivastigmine administered
at standard doses for Alzheimerrsquos disease for 2 to
4 years)537-40 In one trial evaluating the effects of
high-dose vitamin E (2000 IU daily) or donepezil
in persons with mild cognitive impairment do-
nep ezil signif icantly reduced the risk of pro-
gression to Alzheimerrsquos disease for the f irst 12
months of the study (and for up to 24 months in
the subgroup of subjects who were carriers of
APOE ε4) but had no signif icant effect on the
risk of Alz heimerrsquos disease at 36 months which
was the primary study outcome vitamin E did
not signif icantly reduce the risk of progression
at any time point assessed5
A B C
Figure 2 Coronal MRI Scans from Patients with Normal Cognition Mild Cognitive Impairment and Alzheimerrsquos
Disease
The arrows depict the hippocampal formations and the progressive atrophy characterizing the progression from nor-
mal cognition (Panel A) to mild cognitive impairment (Panel B) to Alzheimerrsquos disease (Panel C)
The New England Journal of Medicine
Downloaded from nejmorg at UECE on July 24 2016 For personal use only No other uses without permission
Copyright copy 2011 Massachusetts Medical Society All rights reserved
cl i n i cal pr act i ce
n engl j med 36423 nejmor g june 9 2011 2231
One potential explanation for the apparent lack
of eff icacy in the clinical trials of interventions in
persons with mild cognitive impairment mdash other
than a true absence of drug eff icacy mdash concerns
the heterogeneity of the subjects As the diagnos-
tic threshold moves to an earlier point in the clini-
cal spectrum of cognitive impairment the subtle
changes in cognition could be due to a variety of
causes other than a degenerative brain disease
making it diff icult to determine whether an inter-
vention has had a signif icant effect
There is some evidence of a potential benefit
from cognitive rehabilitation including the use of
mnemonics association strategies and computer-
assisted training programs4142 A recent systematic
review of the literature on cognitive rehabilitation
programs for persons with mild cognitive impair-
ment including some data from randomized clin-
ical trials showed signif icant improvement in
cognitive function at the end of training42
Observational data have shown associations
between the presence of cardiovascular risk factors
in patients with mild cognitive impairment and an
increased risk of progression to dementia7 Such
risk factors should be addressed although there
is no definitive evidence that modif ication of risk
factors slows disease progression In a randomized
trial that used the Cognitive Subscale of the Alz-
heimerrsquos Disease Assessment Scale to compare the
effect of a physical exercise program (brisk walking
for 150 minutes per week) with that of usual care
and education in persons with subjective memory
loss the exercise group had better cognitive func-
tion at 6 months (the primary study outcome) with
some residual benefit noted at 18 months43
Ar eas o f Un cer t ai n t y
More data are needed regarding the usefulness of
various potential predictors of progression to de-
mentia and their role in clinical practice Further
data on these concerns are awaited from the Alz-
heimerrsquos Disease Neuroimaging Initiative under
way in the United States and Canada2744 and from
similar ongoing studies in Japan Europe and Aus-
tralia Some of the goals of these studies are to
better understand the role of MRI f indings (eg
hippocampal atrophy)2245 f indings on 18FDG-PET
(patterns of hypometabolism in the brain) cere-
brospinal f luid markers (levels of Aβ42 and tau)
and f indings on molecular imaging (amyloid
plaques in the brain) in identifying the subgroup
of persons with amnestic mild cognitive impair-
ment who are likely to undergo progression to
clinical Alz hei merrsquos disease274647 Major challeng-
es are to determine optimal cutoff points for these
tests and to compare their relative reliability (alone
and in combination) Randomized trials are need-
ed to assess the potential benefits of pharmaco-
logic and lifestyle interventions in persons with
mild cognitive impairment who are predicted to
be at high risk for rapid progression to Alzheimerrsquos
A B C
Figure 3 Axial Scans of the Brain Obtained with Positron-Emission Tomography and the Use of Amyloid-Binding
Carbon 11ndashLabeled Pittsburgh Compound B
The yellow and red areas indicate retention of the amyloid-binding tracer reflecting amyloid deposits The patient
with normal cognition (Panel A) has no tracer retention whereas the patient with amnestic mild cognitive impair-
ment has an intermediate amount of tracer retention (Panel B) and the patient with Alzheimerrsquos disease has promi-
nent tracer retention (Panel C)
The New England Journal of Medicine
Downloaded from nejmorg at UECE on July 24 2016 For personal use only No other uses without permission
Copyright copy 2011 Massachusetts Medical Society All rights reserved
Outros Marcadores
bull Liacutequor
bull Dosagem de TAU (decaacuteda de 90)
bull Dosagem de AB-42
bull Growdon 1999 (AB-42 e TAU na DA)
Mattsson N et al 2009 JAMA
bull 750 pacientes com Comprometimento Cognitivo Leve
bull Seguimento por 2 anos
bull 271 evoluiram para DA
bull 59 apresentaram outras demecircncias
bull Baixos niacuteveis de Aβ-42 e altos de Fosfo-Tau com maior
acuraacutecia para evoluccedilatildeo para DA
bull 74 pacientes com Doenccedila de Alzheimer x 142 com
Comprometimento Cognitivo Leve e 82 controles
bull Hipometabolismo
- Precuneos
- Ciacutengulo Posterior
- Coacutertex Temporo-parietal
- Coacutertex Frontal
Koivunen et al Neurology 2011
bull 29 pacientes acompanhados por 2 anos
bull Avaliaccedilatildeo de PET com PIB e RM (Atrofia de
hipocampo)
bull 1729 converteram
bull Maior depoacutesito de PIB Ciacutengulo Posterior frontal lateral
temporal e putamem com maior atrofia
bull Pouca modificaccedilao no PIB em 2 anos
bull Aumento da atrofia
Hipoacutetese da Evoluccedilatildeo Temporal
dos processos fisiopatoloacutegicos
Biomarcador e CCL
Criteacuterios para Pesquisa DA
Porque utilizar biomarcador empacientes com quadros cognitivos
bull O paciente vai piorar dos sintomas cognitivos
bull Existe um processo patoloacutegico jaacute conhecido
bull Existe dano neuronal Topografia
bull Falsos positivos o que fazer
Ressonacircncia Magneacutetica de Cracircnio
bull Atrofia hipocampal
bull Casos leves ou assintomaacuteticos
bull Avaliaccedilatildeo de espessura cortical (Walhovd K et al 2010)
bull DTI (Sexton C et al 2011)
Ressonacircncia Magneacutetica
Vantagens
bull Disponibilidade
bull Visualizaccedilatildeo de atrofia
bull Possibilidade de vaacuterias mediccedilotildees
Limitaccedilotildees
bull Teacutecnicas habituaispoucos sensiacuteveis paraquadros leves
bull Reflete somente o danoneuronal
bull Teacutecnicas especiaispouca disponibilidade
Caso
bull RM laudo normal
PET-FDG
Vantagens
bull Sensibilidade
bull Reflete dano neuronal
Limitaccedilotildees
bull Custo
bull Sem ponto de corte
bull Natildeo especiacutefico do dano patoloacutegico
Caso
bull PET-FDG hipometabolismo FTP esquerdo e leve a Direita frontal e parietal
bull O que esse laudo mostra
bull Que eu consegui examinar e topografar direito
PET Amiloide
bull Dificuldades Iniciais
bull Marcador a base de Fluor
PET Tau and Amyloid-β Burden in Mild Alzheimers Disease Divergent Relationshipwith Age Cognition and Cerebrospinal Fluid BiomarkersKoychev I1 Gunn RN23 Firouzian A2 Lawson J1 Zamboni G1 Ridha B4 Sahakian BJ5 Rowe JB6 Thomas A7 Rochester L7 Ffytche D8 Howard R9 Zetterberg H9101112 MacKay C1 Lovestone S1 Deep and Frequent Phenotyping study team
J Alzheimers Dis 2017 Aug 8
PET Marcador Amiloacuteide
Vantagens
bull Refletem o processo patoloacutegico
bull Conseguem detectar indiviacuteduos assintomaacuteticos em risco
bull Predizem piora cliacutenica
Limitaccedilotildees
bull Custo
bull Disponibilidade
bull Normalizaccedilatildeo de pontos de corte
Caso
bull PET-Amiloacuteide
241 Estudos
11341 Pacientes
7086 Pacientes
Entatildeo vamos coletar Liacutequor para todos
Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory ClinicPatients in a Prospective CohortHandels RL12 Joore MA23 Vos SJ1 Aalten P1 Ramakers IH1 Rikkert MO4 Scheltens P5 Jansen WJ1 Visser PJ15 van Berckel BM5 van Domburg P6 Smid M7 Hoff E8 Hoogmoed J910 Bouwman F5 Claassen J4 Leentjens AF1 Wolfs CA1 Severens JL11 Verhey FR1Author information
bull 200 DA
bull 16 DA prodromica
bull 69 DFT
bull 59 DCB
bull 16 PSP
bull 44 DCL
bull 22 ACP
bull 41 Demecircncia Semacircntica
bull 52 Afasias logopecircnicas
bull 11 Afasias natildeo fluentes
bull 71 Depressatildeo
bull 49 Queixa subjetiva de memoacuteria
bull DA -100
bull DA prodromica-100
bull 439 dos outros pacientes tbpositivos
bull 818 ACP
bull 788 Afasia logopecircnica
bull 50 DCL
bull 458 DCB
bull 454 afasias natildeo fluentes
bull 366 demecircncia semacircnticas
bull 145 das DFT
bull 117 (Depressatildeo e QSM)
E o teste de Memoacuteria
bull Sensibilidade100
bull Especificidade de 748
bull Intrusotildees Sensibilidade de 83 e Especificidade72
bull 273 tinham deacuteficit hipocampal
bull 366 dos deprimidos
bull 40 DCL
bull 375 PSP
bull 319 DFT
bull 273 Afasia natildeo fluente
bull 227 ACP
bull 22 Demecircncia Semacircntica
bull 22 DCB
bull 58 Afasia logopecircnica
Existiu uma correlaccedilatildeo desempenho com os marcadores
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
Hipoacutetese Diagnoacutestica
bull Degeneraccedilatildeo Cortico-Basal
bull Doenccedila de Alzheimer atiacutepica
E agora
Exames Complementares nas Demecircncias
bull Descartar causas secundaacuterias
bull Padrotildees especiacuteficos de atrofia
Nova Visatildeo
bull Diferenciaccedilatildeo dos tipos de demecircncia
bull Diagnoacutestico precoce
bull Marcador de evoluccedilatildeo
bull Resposta terapecircutica
Ressonacircncia Magneacuteticabull Natildeo deve ser mais utilizado como somente para
excluir causas secundaacuterias
bull Eacute um biomarcador de dano neuronal
bull Avaliar com cuidado atrofias assimeacutetricas
The n ew en g l an d j o u r n a l of med i c i n e
n engl j med 36423 nejmor g june 9 20112230
A Swedish study showed that subjects with mild
cognitive impairment who had low levels of
β-amyloid peptide 42 (Aβ42) and elevated levels
of tau protein in cerebrospinal f luid were sig-
nif icantly more likely to undergo progression to
Alzheimerrsquos disease than subjects without this
prof ile (hazard ratio 177 95 conf idence inter-
val 53 to 589) a similar relative risk of progres-
sion was associated with a low ratio of Aβ42 to
tau in the cerebrospinal f luid28 An international
multicenter study of 750 subjects with mild cogni-
tive impairment corroborated these general f ind-
ings2930 but used different cutoff points for ab-
normal f indings The reliability of these markers
is highly variable across laboratories standard-
ization will be needed before they are considered
for incorporation into routine care
The use of molecular imaging particularly of
amyloid plaques in the brain (Fig 3) has also been
studied as a possible approach to risk stratif ica-
tion31-33 In several studies subjects with mild cog-
nitive impairment in whom amyloid was detected
on positron-emission tomography (PET) with the
use of the amyloid-binding carbon 11ndashlabeled Pitts-
burgh compound B had more rapid progression to
Alzheimerrsquos disease than did subjects in whom
amyloid was not detected34 The rationale for using
this technique to predict disease progression is that
the presence of amyloid in a patient with mild
cognitive impairment is likely to indicate that the
patient has early Alzheimerrsquos disease however
amyloid has been detected on autopsy in clinical-
ly normal persons indicating that the predictive
value of this measure requires further study35
Management
From a clinical perspective patients with mild cog-
nitive impairment should not be labeled as having
early Alzheimerrsquos disease prodromal Alzheimerrsquos
disease or mild cognitive impairment of the Alz-
heimerrsquos disease type since the patient and fam-
ily are likely to hear only ―Alzheimerrsquos disease and
not appreciate the uncertainty of the association
with Alzheimerrsquos disease36 Clinicians should make
it clear that mild cognitive impairment is an abnor-
mal condition but that the precise outcome is not
certain
At present no medication intended for the
treatment of mild cognitive impairment has been
approved by the Food and Drug Administration
(FDA) In several placebo-controlled clinical trials
there was no signif icant reduction in rates of
progression to dementia among patients with
mild cognitive impairment who were treated with
agents used to treat Alzheimerrsquos disease (donepe-
zil galantamine and rivastigmine administered
at standard doses for Alzheimerrsquos disease for 2 to
4 years)537-40 In one trial evaluating the effects of
high-dose vitamin E (2000 IU daily) or donepezil
in persons with mild cognitive impairment do-
nep ezil signif icantly reduced the risk of pro-
gression to Alzheimerrsquos disease for the f irst 12
months of the study (and for up to 24 months in
the subgroup of subjects who were carriers of
APOE ε4) but had no signif icant effect on the
risk of Alz heimerrsquos disease at 36 months which
was the primary study outcome vitamin E did
not signif icantly reduce the risk of progression
at any time point assessed5
A B C
Figure 2 Coronal MRI Scans from Patients with Normal Cognition Mild Cognitive Impairment and Alzheimerrsquos
Disease
The arrows depict the hippocampal formations and the progressive atrophy characterizing the progression from nor-
mal cognition (Panel A) to mild cognitive impairment (Panel B) to Alzheimerrsquos disease (Panel C)
The New England Journal of Medicine
Downloaded from nejmorg at UECE on July 24 2016 For personal use only No other uses without permission
Copyright copy 2011 Massachusetts Medical Society All rights reserved
cl i n i cal pr act i ce
n engl j med 36423 nejmor g june 9 2011 2231
One potential explanation for the apparent lack
of eff icacy in the clinical trials of interventions in
persons with mild cognitive impairment mdash other
than a true absence of drug eff icacy mdash concerns
the heterogeneity of the subjects As the diagnos-
tic threshold moves to an earlier point in the clini-
cal spectrum of cognitive impairment the subtle
changes in cognition could be due to a variety of
causes other than a degenerative brain disease
making it diff icult to determine whether an inter-
vention has had a signif icant effect
There is some evidence of a potential benefit
from cognitive rehabilitation including the use of
mnemonics association strategies and computer-
assisted training programs4142 A recent systematic
review of the literature on cognitive rehabilitation
programs for persons with mild cognitive impair-
ment including some data from randomized clin-
ical trials showed signif icant improvement in
cognitive function at the end of training42
Observational data have shown associations
between the presence of cardiovascular risk factors
in patients with mild cognitive impairment and an
increased risk of progression to dementia7 Such
risk factors should be addressed although there
is no definitive evidence that modif ication of risk
factors slows disease progression In a randomized
trial that used the Cognitive Subscale of the Alz-
heimerrsquos Disease Assessment Scale to compare the
effect of a physical exercise program (brisk walking
for 150 minutes per week) with that of usual care
and education in persons with subjective memory
loss the exercise group had better cognitive func-
tion at 6 months (the primary study outcome) with
some residual benefit noted at 18 months43
Ar eas o f Un cer t ai n t y
More data are needed regarding the usefulness of
various potential predictors of progression to de-
mentia and their role in clinical practice Further
data on these concerns are awaited from the Alz-
heimerrsquos Disease Neuroimaging Initiative under
way in the United States and Canada2744 and from
similar ongoing studies in Japan Europe and Aus-
tralia Some of the goals of these studies are to
better understand the role of MRI f indings (eg
hippocampal atrophy)2245 f indings on 18FDG-PET
(patterns of hypometabolism in the brain) cere-
brospinal f luid markers (levels of Aβ42 and tau)
and f indings on molecular imaging (amyloid
plaques in the brain) in identifying the subgroup
of persons with amnestic mild cognitive impair-
ment who are likely to undergo progression to
clinical Alz hei merrsquos disease274647 Major challeng-
es are to determine optimal cutoff points for these
tests and to compare their relative reliability (alone
and in combination) Randomized trials are need-
ed to assess the potential benefits of pharmaco-
logic and lifestyle interventions in persons with
mild cognitive impairment who are predicted to
be at high risk for rapid progression to Alzheimerrsquos
A B C
Figure 3 Axial Scans of the Brain Obtained with Positron-Emission Tomography and the Use of Amyloid-Binding
Carbon 11ndashLabeled Pittsburgh Compound B
The yellow and red areas indicate retention of the amyloid-binding tracer reflecting amyloid deposits The patient
with normal cognition (Panel A) has no tracer retention whereas the patient with amnestic mild cognitive impair-
ment has an intermediate amount of tracer retention (Panel B) and the patient with Alzheimerrsquos disease has promi-
nent tracer retention (Panel C)
The New England Journal of Medicine
Downloaded from nejmorg at UECE on July 24 2016 For personal use only No other uses without permission
Copyright copy 2011 Massachusetts Medical Society All rights reserved
Outros Marcadores
bull Liacutequor
bull Dosagem de TAU (decaacuteda de 90)
bull Dosagem de AB-42
bull Growdon 1999 (AB-42 e TAU na DA)
Mattsson N et al 2009 JAMA
bull 750 pacientes com Comprometimento Cognitivo Leve
bull Seguimento por 2 anos
bull 271 evoluiram para DA
bull 59 apresentaram outras demecircncias
bull Baixos niacuteveis de Aβ-42 e altos de Fosfo-Tau com maior
acuraacutecia para evoluccedilatildeo para DA
bull 74 pacientes com Doenccedila de Alzheimer x 142 com
Comprometimento Cognitivo Leve e 82 controles
bull Hipometabolismo
- Precuneos
- Ciacutengulo Posterior
- Coacutertex Temporo-parietal
- Coacutertex Frontal
Koivunen et al Neurology 2011
bull 29 pacientes acompanhados por 2 anos
bull Avaliaccedilatildeo de PET com PIB e RM (Atrofia de
hipocampo)
bull 1729 converteram
bull Maior depoacutesito de PIB Ciacutengulo Posterior frontal lateral
temporal e putamem com maior atrofia
bull Pouca modificaccedilao no PIB em 2 anos
bull Aumento da atrofia
Hipoacutetese da Evoluccedilatildeo Temporal
dos processos fisiopatoloacutegicos
Biomarcador e CCL
Criteacuterios para Pesquisa DA
Porque utilizar biomarcador empacientes com quadros cognitivos
bull O paciente vai piorar dos sintomas cognitivos
bull Existe um processo patoloacutegico jaacute conhecido
bull Existe dano neuronal Topografia
bull Falsos positivos o que fazer
Ressonacircncia Magneacutetica de Cracircnio
bull Atrofia hipocampal
bull Casos leves ou assintomaacuteticos
bull Avaliaccedilatildeo de espessura cortical (Walhovd K et al 2010)
bull DTI (Sexton C et al 2011)
Ressonacircncia Magneacutetica
Vantagens
bull Disponibilidade
bull Visualizaccedilatildeo de atrofia
bull Possibilidade de vaacuterias mediccedilotildees
Limitaccedilotildees
bull Teacutecnicas habituaispoucos sensiacuteveis paraquadros leves
bull Reflete somente o danoneuronal
bull Teacutecnicas especiaispouca disponibilidade
Caso
bull RM laudo normal
PET-FDG
Vantagens
bull Sensibilidade
bull Reflete dano neuronal
Limitaccedilotildees
bull Custo
bull Sem ponto de corte
bull Natildeo especiacutefico do dano patoloacutegico
Caso
bull PET-FDG hipometabolismo FTP esquerdo e leve a Direita frontal e parietal
bull O que esse laudo mostra
bull Que eu consegui examinar e topografar direito
PET Amiloide
bull Dificuldades Iniciais
bull Marcador a base de Fluor
PET Tau and Amyloid-β Burden in Mild Alzheimers Disease Divergent Relationshipwith Age Cognition and Cerebrospinal Fluid BiomarkersKoychev I1 Gunn RN23 Firouzian A2 Lawson J1 Zamboni G1 Ridha B4 Sahakian BJ5 Rowe JB6 Thomas A7 Rochester L7 Ffytche D8 Howard R9 Zetterberg H9101112 MacKay C1 Lovestone S1 Deep and Frequent Phenotyping study team
J Alzheimers Dis 2017 Aug 8
PET Marcador Amiloacuteide
Vantagens
bull Refletem o processo patoloacutegico
bull Conseguem detectar indiviacuteduos assintomaacuteticos em risco
bull Predizem piora cliacutenica
Limitaccedilotildees
bull Custo
bull Disponibilidade
bull Normalizaccedilatildeo de pontos de corte
Caso
bull PET-Amiloacuteide
241 Estudos
11341 Pacientes
7086 Pacientes
Entatildeo vamos coletar Liacutequor para todos
Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory ClinicPatients in a Prospective CohortHandels RL12 Joore MA23 Vos SJ1 Aalten P1 Ramakers IH1 Rikkert MO4 Scheltens P5 Jansen WJ1 Visser PJ15 van Berckel BM5 van Domburg P6 Smid M7 Hoff E8 Hoogmoed J910 Bouwman F5 Claassen J4 Leentjens AF1 Wolfs CA1 Severens JL11 Verhey FR1Author information
bull 200 DA
bull 16 DA prodromica
bull 69 DFT
bull 59 DCB
bull 16 PSP
bull 44 DCL
bull 22 ACP
bull 41 Demecircncia Semacircntica
bull 52 Afasias logopecircnicas
bull 11 Afasias natildeo fluentes
bull 71 Depressatildeo
bull 49 Queixa subjetiva de memoacuteria
bull DA -100
bull DA prodromica-100
bull 439 dos outros pacientes tbpositivos
bull 818 ACP
bull 788 Afasia logopecircnica
bull 50 DCL
bull 458 DCB
bull 454 afasias natildeo fluentes
bull 366 demecircncia semacircnticas
bull 145 das DFT
bull 117 (Depressatildeo e QSM)
E o teste de Memoacuteria
bull Sensibilidade100
bull Especificidade de 748
bull Intrusotildees Sensibilidade de 83 e Especificidade72
bull 273 tinham deacuteficit hipocampal
bull 366 dos deprimidos
bull 40 DCL
bull 375 PSP
bull 319 DFT
bull 273 Afasia natildeo fluente
bull 227 ACP
bull 22 Demecircncia Semacircntica
bull 22 DCB
bull 58 Afasia logopecircnica
Existiu uma correlaccedilatildeo desempenho com os marcadores
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
E agora
Exames Complementares nas Demecircncias
bull Descartar causas secundaacuterias
bull Padrotildees especiacuteficos de atrofia
Nova Visatildeo
bull Diferenciaccedilatildeo dos tipos de demecircncia
bull Diagnoacutestico precoce
bull Marcador de evoluccedilatildeo
bull Resposta terapecircutica
Ressonacircncia Magneacuteticabull Natildeo deve ser mais utilizado como somente para
excluir causas secundaacuterias
bull Eacute um biomarcador de dano neuronal
bull Avaliar com cuidado atrofias assimeacutetricas
The n ew en g l an d j o u r n a l of med i c i n e
n engl j med 36423 nejmor g june 9 20112230
A Swedish study showed that subjects with mild
cognitive impairment who had low levels of
β-amyloid peptide 42 (Aβ42) and elevated levels
of tau protein in cerebrospinal f luid were sig-
nif icantly more likely to undergo progression to
Alzheimerrsquos disease than subjects without this
prof ile (hazard ratio 177 95 conf idence inter-
val 53 to 589) a similar relative risk of progres-
sion was associated with a low ratio of Aβ42 to
tau in the cerebrospinal f luid28 An international
multicenter study of 750 subjects with mild cogni-
tive impairment corroborated these general f ind-
ings2930 but used different cutoff points for ab-
normal f indings The reliability of these markers
is highly variable across laboratories standard-
ization will be needed before they are considered
for incorporation into routine care
The use of molecular imaging particularly of
amyloid plaques in the brain (Fig 3) has also been
studied as a possible approach to risk stratif ica-
tion31-33 In several studies subjects with mild cog-
nitive impairment in whom amyloid was detected
on positron-emission tomography (PET) with the
use of the amyloid-binding carbon 11ndashlabeled Pitts-
burgh compound B had more rapid progression to
Alzheimerrsquos disease than did subjects in whom
amyloid was not detected34 The rationale for using
this technique to predict disease progression is that
the presence of amyloid in a patient with mild
cognitive impairment is likely to indicate that the
patient has early Alzheimerrsquos disease however
amyloid has been detected on autopsy in clinical-
ly normal persons indicating that the predictive
value of this measure requires further study35
Management
From a clinical perspective patients with mild cog-
nitive impairment should not be labeled as having
early Alzheimerrsquos disease prodromal Alzheimerrsquos
disease or mild cognitive impairment of the Alz-
heimerrsquos disease type since the patient and fam-
ily are likely to hear only ―Alzheimerrsquos disease and
not appreciate the uncertainty of the association
with Alzheimerrsquos disease36 Clinicians should make
it clear that mild cognitive impairment is an abnor-
mal condition but that the precise outcome is not
certain
At present no medication intended for the
treatment of mild cognitive impairment has been
approved by the Food and Drug Administration
(FDA) In several placebo-controlled clinical trials
there was no signif icant reduction in rates of
progression to dementia among patients with
mild cognitive impairment who were treated with
agents used to treat Alzheimerrsquos disease (donepe-
zil galantamine and rivastigmine administered
at standard doses for Alzheimerrsquos disease for 2 to
4 years)537-40 In one trial evaluating the effects of
high-dose vitamin E (2000 IU daily) or donepezil
in persons with mild cognitive impairment do-
nep ezil signif icantly reduced the risk of pro-
gression to Alzheimerrsquos disease for the f irst 12
months of the study (and for up to 24 months in
the subgroup of subjects who were carriers of
APOE ε4) but had no signif icant effect on the
risk of Alz heimerrsquos disease at 36 months which
was the primary study outcome vitamin E did
not signif icantly reduce the risk of progression
at any time point assessed5
A B C
Figure 2 Coronal MRI Scans from Patients with Normal Cognition Mild Cognitive Impairment and Alzheimerrsquos
Disease
The arrows depict the hippocampal formations and the progressive atrophy characterizing the progression from nor-
mal cognition (Panel A) to mild cognitive impairment (Panel B) to Alzheimerrsquos disease (Panel C)
The New England Journal of Medicine
Downloaded from nejmorg at UECE on July 24 2016 For personal use only No other uses without permission
Copyright copy 2011 Massachusetts Medical Society All rights reserved
cl i n i cal pr act i ce
n engl j med 36423 nejmor g june 9 2011 2231
One potential explanation for the apparent lack
of eff icacy in the clinical trials of interventions in
persons with mild cognitive impairment mdash other
than a true absence of drug eff icacy mdash concerns
the heterogeneity of the subjects As the diagnos-
tic threshold moves to an earlier point in the clini-
cal spectrum of cognitive impairment the subtle
changes in cognition could be due to a variety of
causes other than a degenerative brain disease
making it diff icult to determine whether an inter-
vention has had a signif icant effect
There is some evidence of a potential benefit
from cognitive rehabilitation including the use of
mnemonics association strategies and computer-
assisted training programs4142 A recent systematic
review of the literature on cognitive rehabilitation
programs for persons with mild cognitive impair-
ment including some data from randomized clin-
ical trials showed signif icant improvement in
cognitive function at the end of training42
Observational data have shown associations
between the presence of cardiovascular risk factors
in patients with mild cognitive impairment and an
increased risk of progression to dementia7 Such
risk factors should be addressed although there
is no definitive evidence that modif ication of risk
factors slows disease progression In a randomized
trial that used the Cognitive Subscale of the Alz-
heimerrsquos Disease Assessment Scale to compare the
effect of a physical exercise program (brisk walking
for 150 minutes per week) with that of usual care
and education in persons with subjective memory
loss the exercise group had better cognitive func-
tion at 6 months (the primary study outcome) with
some residual benefit noted at 18 months43
Ar eas o f Un cer t ai n t y
More data are needed regarding the usefulness of
various potential predictors of progression to de-
mentia and their role in clinical practice Further
data on these concerns are awaited from the Alz-
heimerrsquos Disease Neuroimaging Initiative under
way in the United States and Canada2744 and from
similar ongoing studies in Japan Europe and Aus-
tralia Some of the goals of these studies are to
better understand the role of MRI f indings (eg
hippocampal atrophy)2245 f indings on 18FDG-PET
(patterns of hypometabolism in the brain) cere-
brospinal f luid markers (levels of Aβ42 and tau)
and f indings on molecular imaging (amyloid
plaques in the brain) in identifying the subgroup
of persons with amnestic mild cognitive impair-
ment who are likely to undergo progression to
clinical Alz hei merrsquos disease274647 Major challeng-
es are to determine optimal cutoff points for these
tests and to compare their relative reliability (alone
and in combination) Randomized trials are need-
ed to assess the potential benefits of pharmaco-
logic and lifestyle interventions in persons with
mild cognitive impairment who are predicted to
be at high risk for rapid progression to Alzheimerrsquos
A B C
Figure 3 Axial Scans of the Brain Obtained with Positron-Emission Tomography and the Use of Amyloid-Binding
Carbon 11ndashLabeled Pittsburgh Compound B
The yellow and red areas indicate retention of the amyloid-binding tracer reflecting amyloid deposits The patient
with normal cognition (Panel A) has no tracer retention whereas the patient with amnestic mild cognitive impair-
ment has an intermediate amount of tracer retention (Panel B) and the patient with Alzheimerrsquos disease has promi-
nent tracer retention (Panel C)
The New England Journal of Medicine
Downloaded from nejmorg at UECE on July 24 2016 For personal use only No other uses without permission
Copyright copy 2011 Massachusetts Medical Society All rights reserved
Outros Marcadores
bull Liacutequor
bull Dosagem de TAU (decaacuteda de 90)
bull Dosagem de AB-42
bull Growdon 1999 (AB-42 e TAU na DA)
Mattsson N et al 2009 JAMA
bull 750 pacientes com Comprometimento Cognitivo Leve
bull Seguimento por 2 anos
bull 271 evoluiram para DA
bull 59 apresentaram outras demecircncias
bull Baixos niacuteveis de Aβ-42 e altos de Fosfo-Tau com maior
acuraacutecia para evoluccedilatildeo para DA
bull 74 pacientes com Doenccedila de Alzheimer x 142 com
Comprometimento Cognitivo Leve e 82 controles
bull Hipometabolismo
- Precuneos
- Ciacutengulo Posterior
- Coacutertex Temporo-parietal
- Coacutertex Frontal
Koivunen et al Neurology 2011
bull 29 pacientes acompanhados por 2 anos
bull Avaliaccedilatildeo de PET com PIB e RM (Atrofia de
hipocampo)
bull 1729 converteram
bull Maior depoacutesito de PIB Ciacutengulo Posterior frontal lateral
temporal e putamem com maior atrofia
bull Pouca modificaccedilao no PIB em 2 anos
bull Aumento da atrofia
Hipoacutetese da Evoluccedilatildeo Temporal
dos processos fisiopatoloacutegicos
Biomarcador e CCL
Criteacuterios para Pesquisa DA
Porque utilizar biomarcador empacientes com quadros cognitivos
bull O paciente vai piorar dos sintomas cognitivos
bull Existe um processo patoloacutegico jaacute conhecido
bull Existe dano neuronal Topografia
bull Falsos positivos o que fazer
Ressonacircncia Magneacutetica de Cracircnio
bull Atrofia hipocampal
bull Casos leves ou assintomaacuteticos
bull Avaliaccedilatildeo de espessura cortical (Walhovd K et al 2010)
bull DTI (Sexton C et al 2011)
Ressonacircncia Magneacutetica
Vantagens
bull Disponibilidade
bull Visualizaccedilatildeo de atrofia
bull Possibilidade de vaacuterias mediccedilotildees
Limitaccedilotildees
bull Teacutecnicas habituaispoucos sensiacuteveis paraquadros leves
bull Reflete somente o danoneuronal
bull Teacutecnicas especiaispouca disponibilidade
Caso
bull RM laudo normal
PET-FDG
Vantagens
bull Sensibilidade
bull Reflete dano neuronal
Limitaccedilotildees
bull Custo
bull Sem ponto de corte
bull Natildeo especiacutefico do dano patoloacutegico
Caso
bull PET-FDG hipometabolismo FTP esquerdo e leve a Direita frontal e parietal
bull O que esse laudo mostra
bull Que eu consegui examinar e topografar direito
PET Amiloide
bull Dificuldades Iniciais
bull Marcador a base de Fluor
PET Tau and Amyloid-β Burden in Mild Alzheimers Disease Divergent Relationshipwith Age Cognition and Cerebrospinal Fluid BiomarkersKoychev I1 Gunn RN23 Firouzian A2 Lawson J1 Zamboni G1 Ridha B4 Sahakian BJ5 Rowe JB6 Thomas A7 Rochester L7 Ffytche D8 Howard R9 Zetterberg H9101112 MacKay C1 Lovestone S1 Deep and Frequent Phenotyping study team
J Alzheimers Dis 2017 Aug 8
PET Marcador Amiloacuteide
Vantagens
bull Refletem o processo patoloacutegico
bull Conseguem detectar indiviacuteduos assintomaacuteticos em risco
bull Predizem piora cliacutenica
Limitaccedilotildees
bull Custo
bull Disponibilidade
bull Normalizaccedilatildeo de pontos de corte
Caso
bull PET-Amiloacuteide
241 Estudos
11341 Pacientes
7086 Pacientes
Entatildeo vamos coletar Liacutequor para todos
Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory ClinicPatients in a Prospective CohortHandels RL12 Joore MA23 Vos SJ1 Aalten P1 Ramakers IH1 Rikkert MO4 Scheltens P5 Jansen WJ1 Visser PJ15 van Berckel BM5 van Domburg P6 Smid M7 Hoff E8 Hoogmoed J910 Bouwman F5 Claassen J4 Leentjens AF1 Wolfs CA1 Severens JL11 Verhey FR1Author information
bull 200 DA
bull 16 DA prodromica
bull 69 DFT
bull 59 DCB
bull 16 PSP
bull 44 DCL
bull 22 ACP
bull 41 Demecircncia Semacircntica
bull 52 Afasias logopecircnicas
bull 11 Afasias natildeo fluentes
bull 71 Depressatildeo
bull 49 Queixa subjetiva de memoacuteria
bull DA -100
bull DA prodromica-100
bull 439 dos outros pacientes tbpositivos
bull 818 ACP
bull 788 Afasia logopecircnica
bull 50 DCL
bull 458 DCB
bull 454 afasias natildeo fluentes
bull 366 demecircncia semacircnticas
bull 145 das DFT
bull 117 (Depressatildeo e QSM)
E o teste de Memoacuteria
bull Sensibilidade100
bull Especificidade de 748
bull Intrusotildees Sensibilidade de 83 e Especificidade72
bull 273 tinham deacuteficit hipocampal
bull 366 dos deprimidos
bull 40 DCL
bull 375 PSP
bull 319 DFT
bull 273 Afasia natildeo fluente
bull 227 ACP
bull 22 Demecircncia Semacircntica
bull 22 DCB
bull 58 Afasia logopecircnica
Existiu uma correlaccedilatildeo desempenho com os marcadores
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
Exames Complementares nas Demecircncias
bull Descartar causas secundaacuterias
bull Padrotildees especiacuteficos de atrofia
Nova Visatildeo
bull Diferenciaccedilatildeo dos tipos de demecircncia
bull Diagnoacutestico precoce
bull Marcador de evoluccedilatildeo
bull Resposta terapecircutica
Ressonacircncia Magneacuteticabull Natildeo deve ser mais utilizado como somente para
excluir causas secundaacuterias
bull Eacute um biomarcador de dano neuronal
bull Avaliar com cuidado atrofias assimeacutetricas
The n ew en g l an d j o u r n a l of med i c i n e
n engl j med 36423 nejmor g june 9 20112230
A Swedish study showed that subjects with mild
cognitive impairment who had low levels of
β-amyloid peptide 42 (Aβ42) and elevated levels
of tau protein in cerebrospinal f luid were sig-
nif icantly more likely to undergo progression to
Alzheimerrsquos disease than subjects without this
prof ile (hazard ratio 177 95 conf idence inter-
val 53 to 589) a similar relative risk of progres-
sion was associated with a low ratio of Aβ42 to
tau in the cerebrospinal f luid28 An international
multicenter study of 750 subjects with mild cogni-
tive impairment corroborated these general f ind-
ings2930 but used different cutoff points for ab-
normal f indings The reliability of these markers
is highly variable across laboratories standard-
ization will be needed before they are considered
for incorporation into routine care
The use of molecular imaging particularly of
amyloid plaques in the brain (Fig 3) has also been
studied as a possible approach to risk stratif ica-
tion31-33 In several studies subjects with mild cog-
nitive impairment in whom amyloid was detected
on positron-emission tomography (PET) with the
use of the amyloid-binding carbon 11ndashlabeled Pitts-
burgh compound B had more rapid progression to
Alzheimerrsquos disease than did subjects in whom
amyloid was not detected34 The rationale for using
this technique to predict disease progression is that
the presence of amyloid in a patient with mild
cognitive impairment is likely to indicate that the
patient has early Alzheimerrsquos disease however
amyloid has been detected on autopsy in clinical-
ly normal persons indicating that the predictive
value of this measure requires further study35
Management
From a clinical perspective patients with mild cog-
nitive impairment should not be labeled as having
early Alzheimerrsquos disease prodromal Alzheimerrsquos
disease or mild cognitive impairment of the Alz-
heimerrsquos disease type since the patient and fam-
ily are likely to hear only ―Alzheimerrsquos disease and
not appreciate the uncertainty of the association
with Alzheimerrsquos disease36 Clinicians should make
it clear that mild cognitive impairment is an abnor-
mal condition but that the precise outcome is not
certain
At present no medication intended for the
treatment of mild cognitive impairment has been
approved by the Food and Drug Administration
(FDA) In several placebo-controlled clinical trials
there was no signif icant reduction in rates of
progression to dementia among patients with
mild cognitive impairment who were treated with
agents used to treat Alzheimerrsquos disease (donepe-
zil galantamine and rivastigmine administered
at standard doses for Alzheimerrsquos disease for 2 to
4 years)537-40 In one trial evaluating the effects of
high-dose vitamin E (2000 IU daily) or donepezil
in persons with mild cognitive impairment do-
nep ezil signif icantly reduced the risk of pro-
gression to Alzheimerrsquos disease for the f irst 12
months of the study (and for up to 24 months in
the subgroup of subjects who were carriers of
APOE ε4) but had no signif icant effect on the
risk of Alz heimerrsquos disease at 36 months which
was the primary study outcome vitamin E did
not signif icantly reduce the risk of progression
at any time point assessed5
A B C
Figure 2 Coronal MRI Scans from Patients with Normal Cognition Mild Cognitive Impairment and Alzheimerrsquos
Disease
The arrows depict the hippocampal formations and the progressive atrophy characterizing the progression from nor-
mal cognition (Panel A) to mild cognitive impairment (Panel B) to Alzheimerrsquos disease (Panel C)
The New England Journal of Medicine
Downloaded from nejmorg at UECE on July 24 2016 For personal use only No other uses without permission
Copyright copy 2011 Massachusetts Medical Society All rights reserved
cl i n i cal pr act i ce
n engl j med 36423 nejmor g june 9 2011 2231
One potential explanation for the apparent lack
of eff icacy in the clinical trials of interventions in
persons with mild cognitive impairment mdash other
than a true absence of drug eff icacy mdash concerns
the heterogeneity of the subjects As the diagnos-
tic threshold moves to an earlier point in the clini-
cal spectrum of cognitive impairment the subtle
changes in cognition could be due to a variety of
causes other than a degenerative brain disease
making it diff icult to determine whether an inter-
vention has had a signif icant effect
There is some evidence of a potential benefit
from cognitive rehabilitation including the use of
mnemonics association strategies and computer-
assisted training programs4142 A recent systematic
review of the literature on cognitive rehabilitation
programs for persons with mild cognitive impair-
ment including some data from randomized clin-
ical trials showed signif icant improvement in
cognitive function at the end of training42
Observational data have shown associations
between the presence of cardiovascular risk factors
in patients with mild cognitive impairment and an
increased risk of progression to dementia7 Such
risk factors should be addressed although there
is no definitive evidence that modif ication of risk
factors slows disease progression In a randomized
trial that used the Cognitive Subscale of the Alz-
heimerrsquos Disease Assessment Scale to compare the
effect of a physical exercise program (brisk walking
for 150 minutes per week) with that of usual care
and education in persons with subjective memory
loss the exercise group had better cognitive func-
tion at 6 months (the primary study outcome) with
some residual benefit noted at 18 months43
Ar eas o f Un cer t ai n t y
More data are needed regarding the usefulness of
various potential predictors of progression to de-
mentia and their role in clinical practice Further
data on these concerns are awaited from the Alz-
heimerrsquos Disease Neuroimaging Initiative under
way in the United States and Canada2744 and from
similar ongoing studies in Japan Europe and Aus-
tralia Some of the goals of these studies are to
better understand the role of MRI f indings (eg
hippocampal atrophy)2245 f indings on 18FDG-PET
(patterns of hypometabolism in the brain) cere-
brospinal f luid markers (levels of Aβ42 and tau)
and f indings on molecular imaging (amyloid
plaques in the brain) in identifying the subgroup
of persons with amnestic mild cognitive impair-
ment who are likely to undergo progression to
clinical Alz hei merrsquos disease274647 Major challeng-
es are to determine optimal cutoff points for these
tests and to compare their relative reliability (alone
and in combination) Randomized trials are need-
ed to assess the potential benefits of pharmaco-
logic and lifestyle interventions in persons with
mild cognitive impairment who are predicted to
be at high risk for rapid progression to Alzheimerrsquos
A B C
Figure 3 Axial Scans of the Brain Obtained with Positron-Emission Tomography and the Use of Amyloid-Binding
Carbon 11ndashLabeled Pittsburgh Compound B
The yellow and red areas indicate retention of the amyloid-binding tracer reflecting amyloid deposits The patient
with normal cognition (Panel A) has no tracer retention whereas the patient with amnestic mild cognitive impair-
ment has an intermediate amount of tracer retention (Panel B) and the patient with Alzheimerrsquos disease has promi-
nent tracer retention (Panel C)
The New England Journal of Medicine
Downloaded from nejmorg at UECE on July 24 2016 For personal use only No other uses without permission
Copyright copy 2011 Massachusetts Medical Society All rights reserved
Outros Marcadores
bull Liacutequor
bull Dosagem de TAU (decaacuteda de 90)
bull Dosagem de AB-42
bull Growdon 1999 (AB-42 e TAU na DA)
Mattsson N et al 2009 JAMA
bull 750 pacientes com Comprometimento Cognitivo Leve
bull Seguimento por 2 anos
bull 271 evoluiram para DA
bull 59 apresentaram outras demecircncias
bull Baixos niacuteveis de Aβ-42 e altos de Fosfo-Tau com maior
acuraacutecia para evoluccedilatildeo para DA
bull 74 pacientes com Doenccedila de Alzheimer x 142 com
Comprometimento Cognitivo Leve e 82 controles
bull Hipometabolismo
- Precuneos
- Ciacutengulo Posterior
- Coacutertex Temporo-parietal
- Coacutertex Frontal
Koivunen et al Neurology 2011
bull 29 pacientes acompanhados por 2 anos
bull Avaliaccedilatildeo de PET com PIB e RM (Atrofia de
hipocampo)
bull 1729 converteram
bull Maior depoacutesito de PIB Ciacutengulo Posterior frontal lateral
temporal e putamem com maior atrofia
bull Pouca modificaccedilao no PIB em 2 anos
bull Aumento da atrofia
Hipoacutetese da Evoluccedilatildeo Temporal
dos processos fisiopatoloacutegicos
Biomarcador e CCL
Criteacuterios para Pesquisa DA
Porque utilizar biomarcador empacientes com quadros cognitivos
bull O paciente vai piorar dos sintomas cognitivos
bull Existe um processo patoloacutegico jaacute conhecido
bull Existe dano neuronal Topografia
bull Falsos positivos o que fazer
Ressonacircncia Magneacutetica de Cracircnio
bull Atrofia hipocampal
bull Casos leves ou assintomaacuteticos
bull Avaliaccedilatildeo de espessura cortical (Walhovd K et al 2010)
bull DTI (Sexton C et al 2011)
Ressonacircncia Magneacutetica
Vantagens
bull Disponibilidade
bull Visualizaccedilatildeo de atrofia
bull Possibilidade de vaacuterias mediccedilotildees
Limitaccedilotildees
bull Teacutecnicas habituaispoucos sensiacuteveis paraquadros leves
bull Reflete somente o danoneuronal
bull Teacutecnicas especiaispouca disponibilidade
Caso
bull RM laudo normal
PET-FDG
Vantagens
bull Sensibilidade
bull Reflete dano neuronal
Limitaccedilotildees
bull Custo
bull Sem ponto de corte
bull Natildeo especiacutefico do dano patoloacutegico
Caso
bull PET-FDG hipometabolismo FTP esquerdo e leve a Direita frontal e parietal
bull O que esse laudo mostra
bull Que eu consegui examinar e topografar direito
PET Amiloide
bull Dificuldades Iniciais
bull Marcador a base de Fluor
PET Tau and Amyloid-β Burden in Mild Alzheimers Disease Divergent Relationshipwith Age Cognition and Cerebrospinal Fluid BiomarkersKoychev I1 Gunn RN23 Firouzian A2 Lawson J1 Zamboni G1 Ridha B4 Sahakian BJ5 Rowe JB6 Thomas A7 Rochester L7 Ffytche D8 Howard R9 Zetterberg H9101112 MacKay C1 Lovestone S1 Deep and Frequent Phenotyping study team
J Alzheimers Dis 2017 Aug 8
PET Marcador Amiloacuteide
Vantagens
bull Refletem o processo patoloacutegico
bull Conseguem detectar indiviacuteduos assintomaacuteticos em risco
bull Predizem piora cliacutenica
Limitaccedilotildees
bull Custo
bull Disponibilidade
bull Normalizaccedilatildeo de pontos de corte
Caso
bull PET-Amiloacuteide
241 Estudos
11341 Pacientes
7086 Pacientes
Entatildeo vamos coletar Liacutequor para todos
Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory ClinicPatients in a Prospective CohortHandels RL12 Joore MA23 Vos SJ1 Aalten P1 Ramakers IH1 Rikkert MO4 Scheltens P5 Jansen WJ1 Visser PJ15 van Berckel BM5 van Domburg P6 Smid M7 Hoff E8 Hoogmoed J910 Bouwman F5 Claassen J4 Leentjens AF1 Wolfs CA1 Severens JL11 Verhey FR1Author information
bull 200 DA
bull 16 DA prodromica
bull 69 DFT
bull 59 DCB
bull 16 PSP
bull 44 DCL
bull 22 ACP
bull 41 Demecircncia Semacircntica
bull 52 Afasias logopecircnicas
bull 11 Afasias natildeo fluentes
bull 71 Depressatildeo
bull 49 Queixa subjetiva de memoacuteria
bull DA -100
bull DA prodromica-100
bull 439 dos outros pacientes tbpositivos
bull 818 ACP
bull 788 Afasia logopecircnica
bull 50 DCL
bull 458 DCB
bull 454 afasias natildeo fluentes
bull 366 demecircncia semacircnticas
bull 145 das DFT
bull 117 (Depressatildeo e QSM)
E o teste de Memoacuteria
bull Sensibilidade100
bull Especificidade de 748
bull Intrusotildees Sensibilidade de 83 e Especificidade72
bull 273 tinham deacuteficit hipocampal
bull 366 dos deprimidos
bull 40 DCL
bull 375 PSP
bull 319 DFT
bull 273 Afasia natildeo fluente
bull 227 ACP
bull 22 Demecircncia Semacircntica
bull 22 DCB
bull 58 Afasia logopecircnica
Existiu uma correlaccedilatildeo desempenho com os marcadores
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
Nova Visatildeo
bull Diferenciaccedilatildeo dos tipos de demecircncia
bull Diagnoacutestico precoce
bull Marcador de evoluccedilatildeo
bull Resposta terapecircutica
Ressonacircncia Magneacuteticabull Natildeo deve ser mais utilizado como somente para
excluir causas secundaacuterias
bull Eacute um biomarcador de dano neuronal
bull Avaliar com cuidado atrofias assimeacutetricas
The n ew en g l an d j o u r n a l of med i c i n e
n engl j med 36423 nejmor g june 9 20112230
A Swedish study showed that subjects with mild
cognitive impairment who had low levels of
β-amyloid peptide 42 (Aβ42) and elevated levels
of tau protein in cerebrospinal f luid were sig-
nif icantly more likely to undergo progression to
Alzheimerrsquos disease than subjects without this
prof ile (hazard ratio 177 95 conf idence inter-
val 53 to 589) a similar relative risk of progres-
sion was associated with a low ratio of Aβ42 to
tau in the cerebrospinal f luid28 An international
multicenter study of 750 subjects with mild cogni-
tive impairment corroborated these general f ind-
ings2930 but used different cutoff points for ab-
normal f indings The reliability of these markers
is highly variable across laboratories standard-
ization will be needed before they are considered
for incorporation into routine care
The use of molecular imaging particularly of
amyloid plaques in the brain (Fig 3) has also been
studied as a possible approach to risk stratif ica-
tion31-33 In several studies subjects with mild cog-
nitive impairment in whom amyloid was detected
on positron-emission tomography (PET) with the
use of the amyloid-binding carbon 11ndashlabeled Pitts-
burgh compound B had more rapid progression to
Alzheimerrsquos disease than did subjects in whom
amyloid was not detected34 The rationale for using
this technique to predict disease progression is that
the presence of amyloid in a patient with mild
cognitive impairment is likely to indicate that the
patient has early Alzheimerrsquos disease however
amyloid has been detected on autopsy in clinical-
ly normal persons indicating that the predictive
value of this measure requires further study35
Management
From a clinical perspective patients with mild cog-
nitive impairment should not be labeled as having
early Alzheimerrsquos disease prodromal Alzheimerrsquos
disease or mild cognitive impairment of the Alz-
heimerrsquos disease type since the patient and fam-
ily are likely to hear only ―Alzheimerrsquos disease and
not appreciate the uncertainty of the association
with Alzheimerrsquos disease36 Clinicians should make
it clear that mild cognitive impairment is an abnor-
mal condition but that the precise outcome is not
certain
At present no medication intended for the
treatment of mild cognitive impairment has been
approved by the Food and Drug Administration
(FDA) In several placebo-controlled clinical trials
there was no signif icant reduction in rates of
progression to dementia among patients with
mild cognitive impairment who were treated with
agents used to treat Alzheimerrsquos disease (donepe-
zil galantamine and rivastigmine administered
at standard doses for Alzheimerrsquos disease for 2 to
4 years)537-40 In one trial evaluating the effects of
high-dose vitamin E (2000 IU daily) or donepezil
in persons with mild cognitive impairment do-
nep ezil signif icantly reduced the risk of pro-
gression to Alzheimerrsquos disease for the f irst 12
months of the study (and for up to 24 months in
the subgroup of subjects who were carriers of
APOE ε4) but had no signif icant effect on the
risk of Alz heimerrsquos disease at 36 months which
was the primary study outcome vitamin E did
not signif icantly reduce the risk of progression
at any time point assessed5
A B C
Figure 2 Coronal MRI Scans from Patients with Normal Cognition Mild Cognitive Impairment and Alzheimerrsquos
Disease
The arrows depict the hippocampal formations and the progressive atrophy characterizing the progression from nor-
mal cognition (Panel A) to mild cognitive impairment (Panel B) to Alzheimerrsquos disease (Panel C)
The New England Journal of Medicine
Downloaded from nejmorg at UECE on July 24 2016 For personal use only No other uses without permission
Copyright copy 2011 Massachusetts Medical Society All rights reserved
cl i n i cal pr act i ce
n engl j med 36423 nejmor g june 9 2011 2231
One potential explanation for the apparent lack
of eff icacy in the clinical trials of interventions in
persons with mild cognitive impairment mdash other
than a true absence of drug eff icacy mdash concerns
the heterogeneity of the subjects As the diagnos-
tic threshold moves to an earlier point in the clini-
cal spectrum of cognitive impairment the subtle
changes in cognition could be due to a variety of
causes other than a degenerative brain disease
making it diff icult to determine whether an inter-
vention has had a signif icant effect
There is some evidence of a potential benefit
from cognitive rehabilitation including the use of
mnemonics association strategies and computer-
assisted training programs4142 A recent systematic
review of the literature on cognitive rehabilitation
programs for persons with mild cognitive impair-
ment including some data from randomized clin-
ical trials showed signif icant improvement in
cognitive function at the end of training42
Observational data have shown associations
between the presence of cardiovascular risk factors
in patients with mild cognitive impairment and an
increased risk of progression to dementia7 Such
risk factors should be addressed although there
is no definitive evidence that modif ication of risk
factors slows disease progression In a randomized
trial that used the Cognitive Subscale of the Alz-
heimerrsquos Disease Assessment Scale to compare the
effect of a physical exercise program (brisk walking
for 150 minutes per week) with that of usual care
and education in persons with subjective memory
loss the exercise group had better cognitive func-
tion at 6 months (the primary study outcome) with
some residual benefit noted at 18 months43
Ar eas o f Un cer t ai n t y
More data are needed regarding the usefulness of
various potential predictors of progression to de-
mentia and their role in clinical practice Further
data on these concerns are awaited from the Alz-
heimerrsquos Disease Neuroimaging Initiative under
way in the United States and Canada2744 and from
similar ongoing studies in Japan Europe and Aus-
tralia Some of the goals of these studies are to
better understand the role of MRI f indings (eg
hippocampal atrophy)2245 f indings on 18FDG-PET
(patterns of hypometabolism in the brain) cere-
brospinal f luid markers (levels of Aβ42 and tau)
and f indings on molecular imaging (amyloid
plaques in the brain) in identifying the subgroup
of persons with amnestic mild cognitive impair-
ment who are likely to undergo progression to
clinical Alz hei merrsquos disease274647 Major challeng-
es are to determine optimal cutoff points for these
tests and to compare their relative reliability (alone
and in combination) Randomized trials are need-
ed to assess the potential benefits of pharmaco-
logic and lifestyle interventions in persons with
mild cognitive impairment who are predicted to
be at high risk for rapid progression to Alzheimerrsquos
A B C
Figure 3 Axial Scans of the Brain Obtained with Positron-Emission Tomography and the Use of Amyloid-Binding
Carbon 11ndashLabeled Pittsburgh Compound B
The yellow and red areas indicate retention of the amyloid-binding tracer reflecting amyloid deposits The patient
with normal cognition (Panel A) has no tracer retention whereas the patient with amnestic mild cognitive impair-
ment has an intermediate amount of tracer retention (Panel B) and the patient with Alzheimerrsquos disease has promi-
nent tracer retention (Panel C)
The New England Journal of Medicine
Downloaded from nejmorg at UECE on July 24 2016 For personal use only No other uses without permission
Copyright copy 2011 Massachusetts Medical Society All rights reserved
Outros Marcadores
bull Liacutequor
bull Dosagem de TAU (decaacuteda de 90)
bull Dosagem de AB-42
bull Growdon 1999 (AB-42 e TAU na DA)
Mattsson N et al 2009 JAMA
bull 750 pacientes com Comprometimento Cognitivo Leve
bull Seguimento por 2 anos
bull 271 evoluiram para DA
bull 59 apresentaram outras demecircncias
bull Baixos niacuteveis de Aβ-42 e altos de Fosfo-Tau com maior
acuraacutecia para evoluccedilatildeo para DA
bull 74 pacientes com Doenccedila de Alzheimer x 142 com
Comprometimento Cognitivo Leve e 82 controles
bull Hipometabolismo
- Precuneos
- Ciacutengulo Posterior
- Coacutertex Temporo-parietal
- Coacutertex Frontal
Koivunen et al Neurology 2011
bull 29 pacientes acompanhados por 2 anos
bull Avaliaccedilatildeo de PET com PIB e RM (Atrofia de
hipocampo)
bull 1729 converteram
bull Maior depoacutesito de PIB Ciacutengulo Posterior frontal lateral
temporal e putamem com maior atrofia
bull Pouca modificaccedilao no PIB em 2 anos
bull Aumento da atrofia
Hipoacutetese da Evoluccedilatildeo Temporal
dos processos fisiopatoloacutegicos
Biomarcador e CCL
Criteacuterios para Pesquisa DA
Porque utilizar biomarcador empacientes com quadros cognitivos
bull O paciente vai piorar dos sintomas cognitivos
bull Existe um processo patoloacutegico jaacute conhecido
bull Existe dano neuronal Topografia
bull Falsos positivos o que fazer
Ressonacircncia Magneacutetica de Cracircnio
bull Atrofia hipocampal
bull Casos leves ou assintomaacuteticos
bull Avaliaccedilatildeo de espessura cortical (Walhovd K et al 2010)
bull DTI (Sexton C et al 2011)
Ressonacircncia Magneacutetica
Vantagens
bull Disponibilidade
bull Visualizaccedilatildeo de atrofia
bull Possibilidade de vaacuterias mediccedilotildees
Limitaccedilotildees
bull Teacutecnicas habituaispoucos sensiacuteveis paraquadros leves
bull Reflete somente o danoneuronal
bull Teacutecnicas especiaispouca disponibilidade
Caso
bull RM laudo normal
PET-FDG
Vantagens
bull Sensibilidade
bull Reflete dano neuronal
Limitaccedilotildees
bull Custo
bull Sem ponto de corte
bull Natildeo especiacutefico do dano patoloacutegico
Caso
bull PET-FDG hipometabolismo FTP esquerdo e leve a Direita frontal e parietal
bull O que esse laudo mostra
bull Que eu consegui examinar e topografar direito
PET Amiloide
bull Dificuldades Iniciais
bull Marcador a base de Fluor
PET Tau and Amyloid-β Burden in Mild Alzheimers Disease Divergent Relationshipwith Age Cognition and Cerebrospinal Fluid BiomarkersKoychev I1 Gunn RN23 Firouzian A2 Lawson J1 Zamboni G1 Ridha B4 Sahakian BJ5 Rowe JB6 Thomas A7 Rochester L7 Ffytche D8 Howard R9 Zetterberg H9101112 MacKay C1 Lovestone S1 Deep and Frequent Phenotyping study team
J Alzheimers Dis 2017 Aug 8
PET Marcador Amiloacuteide
Vantagens
bull Refletem o processo patoloacutegico
bull Conseguem detectar indiviacuteduos assintomaacuteticos em risco
bull Predizem piora cliacutenica
Limitaccedilotildees
bull Custo
bull Disponibilidade
bull Normalizaccedilatildeo de pontos de corte
Caso
bull PET-Amiloacuteide
241 Estudos
11341 Pacientes
7086 Pacientes
Entatildeo vamos coletar Liacutequor para todos
Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory ClinicPatients in a Prospective CohortHandels RL12 Joore MA23 Vos SJ1 Aalten P1 Ramakers IH1 Rikkert MO4 Scheltens P5 Jansen WJ1 Visser PJ15 van Berckel BM5 van Domburg P6 Smid M7 Hoff E8 Hoogmoed J910 Bouwman F5 Claassen J4 Leentjens AF1 Wolfs CA1 Severens JL11 Verhey FR1Author information
bull 200 DA
bull 16 DA prodromica
bull 69 DFT
bull 59 DCB
bull 16 PSP
bull 44 DCL
bull 22 ACP
bull 41 Demecircncia Semacircntica
bull 52 Afasias logopecircnicas
bull 11 Afasias natildeo fluentes
bull 71 Depressatildeo
bull 49 Queixa subjetiva de memoacuteria
bull DA -100
bull DA prodromica-100
bull 439 dos outros pacientes tbpositivos
bull 818 ACP
bull 788 Afasia logopecircnica
bull 50 DCL
bull 458 DCB
bull 454 afasias natildeo fluentes
bull 366 demecircncia semacircnticas
bull 145 das DFT
bull 117 (Depressatildeo e QSM)
E o teste de Memoacuteria
bull Sensibilidade100
bull Especificidade de 748
bull Intrusotildees Sensibilidade de 83 e Especificidade72
bull 273 tinham deacuteficit hipocampal
bull 366 dos deprimidos
bull 40 DCL
bull 375 PSP
bull 319 DFT
bull 273 Afasia natildeo fluente
bull 227 ACP
bull 22 Demecircncia Semacircntica
bull 22 DCB
bull 58 Afasia logopecircnica
Existiu uma correlaccedilatildeo desempenho com os marcadores
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
Ressonacircncia Magneacuteticabull Natildeo deve ser mais utilizado como somente para
excluir causas secundaacuterias
bull Eacute um biomarcador de dano neuronal
bull Avaliar com cuidado atrofias assimeacutetricas
The n ew en g l an d j o u r n a l of med i c i n e
n engl j med 36423 nejmor g june 9 20112230
A Swedish study showed that subjects with mild
cognitive impairment who had low levels of
β-amyloid peptide 42 (Aβ42) and elevated levels
of tau protein in cerebrospinal f luid were sig-
nif icantly more likely to undergo progression to
Alzheimerrsquos disease than subjects without this
prof ile (hazard ratio 177 95 conf idence inter-
val 53 to 589) a similar relative risk of progres-
sion was associated with a low ratio of Aβ42 to
tau in the cerebrospinal f luid28 An international
multicenter study of 750 subjects with mild cogni-
tive impairment corroborated these general f ind-
ings2930 but used different cutoff points for ab-
normal f indings The reliability of these markers
is highly variable across laboratories standard-
ization will be needed before they are considered
for incorporation into routine care
The use of molecular imaging particularly of
amyloid plaques in the brain (Fig 3) has also been
studied as a possible approach to risk stratif ica-
tion31-33 In several studies subjects with mild cog-
nitive impairment in whom amyloid was detected
on positron-emission tomography (PET) with the
use of the amyloid-binding carbon 11ndashlabeled Pitts-
burgh compound B had more rapid progression to
Alzheimerrsquos disease than did subjects in whom
amyloid was not detected34 The rationale for using
this technique to predict disease progression is that
the presence of amyloid in a patient with mild
cognitive impairment is likely to indicate that the
patient has early Alzheimerrsquos disease however
amyloid has been detected on autopsy in clinical-
ly normal persons indicating that the predictive
value of this measure requires further study35
Management
From a clinical perspective patients with mild cog-
nitive impairment should not be labeled as having
early Alzheimerrsquos disease prodromal Alzheimerrsquos
disease or mild cognitive impairment of the Alz-
heimerrsquos disease type since the patient and fam-
ily are likely to hear only ―Alzheimerrsquos disease and
not appreciate the uncertainty of the association
with Alzheimerrsquos disease36 Clinicians should make
it clear that mild cognitive impairment is an abnor-
mal condition but that the precise outcome is not
certain
At present no medication intended for the
treatment of mild cognitive impairment has been
approved by the Food and Drug Administration
(FDA) In several placebo-controlled clinical trials
there was no signif icant reduction in rates of
progression to dementia among patients with
mild cognitive impairment who were treated with
agents used to treat Alzheimerrsquos disease (donepe-
zil galantamine and rivastigmine administered
at standard doses for Alzheimerrsquos disease for 2 to
4 years)537-40 In one trial evaluating the effects of
high-dose vitamin E (2000 IU daily) or donepezil
in persons with mild cognitive impairment do-
nep ezil signif icantly reduced the risk of pro-
gression to Alzheimerrsquos disease for the f irst 12
months of the study (and for up to 24 months in
the subgroup of subjects who were carriers of
APOE ε4) but had no signif icant effect on the
risk of Alz heimerrsquos disease at 36 months which
was the primary study outcome vitamin E did
not signif icantly reduce the risk of progression
at any time point assessed5
A B C
Figure 2 Coronal MRI Scans from Patients with Normal Cognition Mild Cognitive Impairment and Alzheimerrsquos
Disease
The arrows depict the hippocampal formations and the progressive atrophy characterizing the progression from nor-
mal cognition (Panel A) to mild cognitive impairment (Panel B) to Alzheimerrsquos disease (Panel C)
The New England Journal of Medicine
Downloaded from nejmorg at UECE on July 24 2016 For personal use only No other uses without permission
Copyright copy 2011 Massachusetts Medical Society All rights reserved
cl i n i cal pr act i ce
n engl j med 36423 nejmor g june 9 2011 2231
One potential explanation for the apparent lack
of eff icacy in the clinical trials of interventions in
persons with mild cognitive impairment mdash other
than a true absence of drug eff icacy mdash concerns
the heterogeneity of the subjects As the diagnos-
tic threshold moves to an earlier point in the clini-
cal spectrum of cognitive impairment the subtle
changes in cognition could be due to a variety of
causes other than a degenerative brain disease
making it diff icult to determine whether an inter-
vention has had a signif icant effect
There is some evidence of a potential benefit
from cognitive rehabilitation including the use of
mnemonics association strategies and computer-
assisted training programs4142 A recent systematic
review of the literature on cognitive rehabilitation
programs for persons with mild cognitive impair-
ment including some data from randomized clin-
ical trials showed signif icant improvement in
cognitive function at the end of training42
Observational data have shown associations
between the presence of cardiovascular risk factors
in patients with mild cognitive impairment and an
increased risk of progression to dementia7 Such
risk factors should be addressed although there
is no definitive evidence that modif ication of risk
factors slows disease progression In a randomized
trial that used the Cognitive Subscale of the Alz-
heimerrsquos Disease Assessment Scale to compare the
effect of a physical exercise program (brisk walking
for 150 minutes per week) with that of usual care
and education in persons with subjective memory
loss the exercise group had better cognitive func-
tion at 6 months (the primary study outcome) with
some residual benefit noted at 18 months43
Ar eas o f Un cer t ai n t y
More data are needed regarding the usefulness of
various potential predictors of progression to de-
mentia and their role in clinical practice Further
data on these concerns are awaited from the Alz-
heimerrsquos Disease Neuroimaging Initiative under
way in the United States and Canada2744 and from
similar ongoing studies in Japan Europe and Aus-
tralia Some of the goals of these studies are to
better understand the role of MRI f indings (eg
hippocampal atrophy)2245 f indings on 18FDG-PET
(patterns of hypometabolism in the brain) cere-
brospinal f luid markers (levels of Aβ42 and tau)
and f indings on molecular imaging (amyloid
plaques in the brain) in identifying the subgroup
of persons with amnestic mild cognitive impair-
ment who are likely to undergo progression to
clinical Alz hei merrsquos disease274647 Major challeng-
es are to determine optimal cutoff points for these
tests and to compare their relative reliability (alone
and in combination) Randomized trials are need-
ed to assess the potential benefits of pharmaco-
logic and lifestyle interventions in persons with
mild cognitive impairment who are predicted to
be at high risk for rapid progression to Alzheimerrsquos
A B C
Figure 3 Axial Scans of the Brain Obtained with Positron-Emission Tomography and the Use of Amyloid-Binding
Carbon 11ndashLabeled Pittsburgh Compound B
The yellow and red areas indicate retention of the amyloid-binding tracer reflecting amyloid deposits The patient
with normal cognition (Panel A) has no tracer retention whereas the patient with amnestic mild cognitive impair-
ment has an intermediate amount of tracer retention (Panel B) and the patient with Alzheimerrsquos disease has promi-
nent tracer retention (Panel C)
The New England Journal of Medicine
Downloaded from nejmorg at UECE on July 24 2016 For personal use only No other uses without permission
Copyright copy 2011 Massachusetts Medical Society All rights reserved
Outros Marcadores
bull Liacutequor
bull Dosagem de TAU (decaacuteda de 90)
bull Dosagem de AB-42
bull Growdon 1999 (AB-42 e TAU na DA)
Mattsson N et al 2009 JAMA
bull 750 pacientes com Comprometimento Cognitivo Leve
bull Seguimento por 2 anos
bull 271 evoluiram para DA
bull 59 apresentaram outras demecircncias
bull Baixos niacuteveis de Aβ-42 e altos de Fosfo-Tau com maior
acuraacutecia para evoluccedilatildeo para DA
bull 74 pacientes com Doenccedila de Alzheimer x 142 com
Comprometimento Cognitivo Leve e 82 controles
bull Hipometabolismo
- Precuneos
- Ciacutengulo Posterior
- Coacutertex Temporo-parietal
- Coacutertex Frontal
Koivunen et al Neurology 2011
bull 29 pacientes acompanhados por 2 anos
bull Avaliaccedilatildeo de PET com PIB e RM (Atrofia de
hipocampo)
bull 1729 converteram
bull Maior depoacutesito de PIB Ciacutengulo Posterior frontal lateral
temporal e putamem com maior atrofia
bull Pouca modificaccedilao no PIB em 2 anos
bull Aumento da atrofia
Hipoacutetese da Evoluccedilatildeo Temporal
dos processos fisiopatoloacutegicos
Biomarcador e CCL
Criteacuterios para Pesquisa DA
Porque utilizar biomarcador empacientes com quadros cognitivos
bull O paciente vai piorar dos sintomas cognitivos
bull Existe um processo patoloacutegico jaacute conhecido
bull Existe dano neuronal Topografia
bull Falsos positivos o que fazer
Ressonacircncia Magneacutetica de Cracircnio
bull Atrofia hipocampal
bull Casos leves ou assintomaacuteticos
bull Avaliaccedilatildeo de espessura cortical (Walhovd K et al 2010)
bull DTI (Sexton C et al 2011)
Ressonacircncia Magneacutetica
Vantagens
bull Disponibilidade
bull Visualizaccedilatildeo de atrofia
bull Possibilidade de vaacuterias mediccedilotildees
Limitaccedilotildees
bull Teacutecnicas habituaispoucos sensiacuteveis paraquadros leves
bull Reflete somente o danoneuronal
bull Teacutecnicas especiaispouca disponibilidade
Caso
bull RM laudo normal
PET-FDG
Vantagens
bull Sensibilidade
bull Reflete dano neuronal
Limitaccedilotildees
bull Custo
bull Sem ponto de corte
bull Natildeo especiacutefico do dano patoloacutegico
Caso
bull PET-FDG hipometabolismo FTP esquerdo e leve a Direita frontal e parietal
bull O que esse laudo mostra
bull Que eu consegui examinar e topografar direito
PET Amiloide
bull Dificuldades Iniciais
bull Marcador a base de Fluor
PET Tau and Amyloid-β Burden in Mild Alzheimers Disease Divergent Relationshipwith Age Cognition and Cerebrospinal Fluid BiomarkersKoychev I1 Gunn RN23 Firouzian A2 Lawson J1 Zamboni G1 Ridha B4 Sahakian BJ5 Rowe JB6 Thomas A7 Rochester L7 Ffytche D8 Howard R9 Zetterberg H9101112 MacKay C1 Lovestone S1 Deep and Frequent Phenotyping study team
J Alzheimers Dis 2017 Aug 8
PET Marcador Amiloacuteide
Vantagens
bull Refletem o processo patoloacutegico
bull Conseguem detectar indiviacuteduos assintomaacuteticos em risco
bull Predizem piora cliacutenica
Limitaccedilotildees
bull Custo
bull Disponibilidade
bull Normalizaccedilatildeo de pontos de corte
Caso
bull PET-Amiloacuteide
241 Estudos
11341 Pacientes
7086 Pacientes
Entatildeo vamos coletar Liacutequor para todos
Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory ClinicPatients in a Prospective CohortHandels RL12 Joore MA23 Vos SJ1 Aalten P1 Ramakers IH1 Rikkert MO4 Scheltens P5 Jansen WJ1 Visser PJ15 van Berckel BM5 van Domburg P6 Smid M7 Hoff E8 Hoogmoed J910 Bouwman F5 Claassen J4 Leentjens AF1 Wolfs CA1 Severens JL11 Verhey FR1Author information
bull 200 DA
bull 16 DA prodromica
bull 69 DFT
bull 59 DCB
bull 16 PSP
bull 44 DCL
bull 22 ACP
bull 41 Demecircncia Semacircntica
bull 52 Afasias logopecircnicas
bull 11 Afasias natildeo fluentes
bull 71 Depressatildeo
bull 49 Queixa subjetiva de memoacuteria
bull DA -100
bull DA prodromica-100
bull 439 dos outros pacientes tbpositivos
bull 818 ACP
bull 788 Afasia logopecircnica
bull 50 DCL
bull 458 DCB
bull 454 afasias natildeo fluentes
bull 366 demecircncia semacircnticas
bull 145 das DFT
bull 117 (Depressatildeo e QSM)
E o teste de Memoacuteria
bull Sensibilidade100
bull Especificidade de 748
bull Intrusotildees Sensibilidade de 83 e Especificidade72
bull 273 tinham deacuteficit hipocampal
bull 366 dos deprimidos
bull 40 DCL
bull 375 PSP
bull 319 DFT
bull 273 Afasia natildeo fluente
bull 227 ACP
bull 22 Demecircncia Semacircntica
bull 22 DCB
bull 58 Afasia logopecircnica
Existiu uma correlaccedilatildeo desempenho com os marcadores
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
Outros Marcadores
bull Liacutequor
bull Dosagem de TAU (decaacuteda de 90)
bull Dosagem de AB-42
bull Growdon 1999 (AB-42 e TAU na DA)
Mattsson N et al 2009 JAMA
bull 750 pacientes com Comprometimento Cognitivo Leve
bull Seguimento por 2 anos
bull 271 evoluiram para DA
bull 59 apresentaram outras demecircncias
bull Baixos niacuteveis de Aβ-42 e altos de Fosfo-Tau com maior
acuraacutecia para evoluccedilatildeo para DA
bull 74 pacientes com Doenccedila de Alzheimer x 142 com
Comprometimento Cognitivo Leve e 82 controles
bull Hipometabolismo
- Precuneos
- Ciacutengulo Posterior
- Coacutertex Temporo-parietal
- Coacutertex Frontal
Koivunen et al Neurology 2011
bull 29 pacientes acompanhados por 2 anos
bull Avaliaccedilatildeo de PET com PIB e RM (Atrofia de
hipocampo)
bull 1729 converteram
bull Maior depoacutesito de PIB Ciacutengulo Posterior frontal lateral
temporal e putamem com maior atrofia
bull Pouca modificaccedilao no PIB em 2 anos
bull Aumento da atrofia
Hipoacutetese da Evoluccedilatildeo Temporal
dos processos fisiopatoloacutegicos
Biomarcador e CCL
Criteacuterios para Pesquisa DA
Porque utilizar biomarcador empacientes com quadros cognitivos
bull O paciente vai piorar dos sintomas cognitivos
bull Existe um processo patoloacutegico jaacute conhecido
bull Existe dano neuronal Topografia
bull Falsos positivos o que fazer
Ressonacircncia Magneacutetica de Cracircnio
bull Atrofia hipocampal
bull Casos leves ou assintomaacuteticos
bull Avaliaccedilatildeo de espessura cortical (Walhovd K et al 2010)
bull DTI (Sexton C et al 2011)
Ressonacircncia Magneacutetica
Vantagens
bull Disponibilidade
bull Visualizaccedilatildeo de atrofia
bull Possibilidade de vaacuterias mediccedilotildees
Limitaccedilotildees
bull Teacutecnicas habituaispoucos sensiacuteveis paraquadros leves
bull Reflete somente o danoneuronal
bull Teacutecnicas especiaispouca disponibilidade
Caso
bull RM laudo normal
PET-FDG
Vantagens
bull Sensibilidade
bull Reflete dano neuronal
Limitaccedilotildees
bull Custo
bull Sem ponto de corte
bull Natildeo especiacutefico do dano patoloacutegico
Caso
bull PET-FDG hipometabolismo FTP esquerdo e leve a Direita frontal e parietal
bull O que esse laudo mostra
bull Que eu consegui examinar e topografar direito
PET Amiloide
bull Dificuldades Iniciais
bull Marcador a base de Fluor
PET Tau and Amyloid-β Burden in Mild Alzheimers Disease Divergent Relationshipwith Age Cognition and Cerebrospinal Fluid BiomarkersKoychev I1 Gunn RN23 Firouzian A2 Lawson J1 Zamboni G1 Ridha B4 Sahakian BJ5 Rowe JB6 Thomas A7 Rochester L7 Ffytche D8 Howard R9 Zetterberg H9101112 MacKay C1 Lovestone S1 Deep and Frequent Phenotyping study team
J Alzheimers Dis 2017 Aug 8
PET Marcador Amiloacuteide
Vantagens
bull Refletem o processo patoloacutegico
bull Conseguem detectar indiviacuteduos assintomaacuteticos em risco
bull Predizem piora cliacutenica
Limitaccedilotildees
bull Custo
bull Disponibilidade
bull Normalizaccedilatildeo de pontos de corte
Caso
bull PET-Amiloacuteide
241 Estudos
11341 Pacientes
7086 Pacientes
Entatildeo vamos coletar Liacutequor para todos
Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory ClinicPatients in a Prospective CohortHandels RL12 Joore MA23 Vos SJ1 Aalten P1 Ramakers IH1 Rikkert MO4 Scheltens P5 Jansen WJ1 Visser PJ15 van Berckel BM5 van Domburg P6 Smid M7 Hoff E8 Hoogmoed J910 Bouwman F5 Claassen J4 Leentjens AF1 Wolfs CA1 Severens JL11 Verhey FR1Author information
bull 200 DA
bull 16 DA prodromica
bull 69 DFT
bull 59 DCB
bull 16 PSP
bull 44 DCL
bull 22 ACP
bull 41 Demecircncia Semacircntica
bull 52 Afasias logopecircnicas
bull 11 Afasias natildeo fluentes
bull 71 Depressatildeo
bull 49 Queixa subjetiva de memoacuteria
bull DA -100
bull DA prodromica-100
bull 439 dos outros pacientes tbpositivos
bull 818 ACP
bull 788 Afasia logopecircnica
bull 50 DCL
bull 458 DCB
bull 454 afasias natildeo fluentes
bull 366 demecircncia semacircnticas
bull 145 das DFT
bull 117 (Depressatildeo e QSM)
E o teste de Memoacuteria
bull Sensibilidade100
bull Especificidade de 748
bull Intrusotildees Sensibilidade de 83 e Especificidade72
bull 273 tinham deacuteficit hipocampal
bull 366 dos deprimidos
bull 40 DCL
bull 375 PSP
bull 319 DFT
bull 273 Afasia natildeo fluente
bull 227 ACP
bull 22 Demecircncia Semacircntica
bull 22 DCB
bull 58 Afasia logopecircnica
Existiu uma correlaccedilatildeo desempenho com os marcadores
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
Mattsson N et al 2009 JAMA
bull 750 pacientes com Comprometimento Cognitivo Leve
bull Seguimento por 2 anos
bull 271 evoluiram para DA
bull 59 apresentaram outras demecircncias
bull Baixos niacuteveis de Aβ-42 e altos de Fosfo-Tau com maior
acuraacutecia para evoluccedilatildeo para DA
bull 74 pacientes com Doenccedila de Alzheimer x 142 com
Comprometimento Cognitivo Leve e 82 controles
bull Hipometabolismo
- Precuneos
- Ciacutengulo Posterior
- Coacutertex Temporo-parietal
- Coacutertex Frontal
Koivunen et al Neurology 2011
bull 29 pacientes acompanhados por 2 anos
bull Avaliaccedilatildeo de PET com PIB e RM (Atrofia de
hipocampo)
bull 1729 converteram
bull Maior depoacutesito de PIB Ciacutengulo Posterior frontal lateral
temporal e putamem com maior atrofia
bull Pouca modificaccedilao no PIB em 2 anos
bull Aumento da atrofia
Hipoacutetese da Evoluccedilatildeo Temporal
dos processos fisiopatoloacutegicos
Biomarcador e CCL
Criteacuterios para Pesquisa DA
Porque utilizar biomarcador empacientes com quadros cognitivos
bull O paciente vai piorar dos sintomas cognitivos
bull Existe um processo patoloacutegico jaacute conhecido
bull Existe dano neuronal Topografia
bull Falsos positivos o que fazer
Ressonacircncia Magneacutetica de Cracircnio
bull Atrofia hipocampal
bull Casos leves ou assintomaacuteticos
bull Avaliaccedilatildeo de espessura cortical (Walhovd K et al 2010)
bull DTI (Sexton C et al 2011)
Ressonacircncia Magneacutetica
Vantagens
bull Disponibilidade
bull Visualizaccedilatildeo de atrofia
bull Possibilidade de vaacuterias mediccedilotildees
Limitaccedilotildees
bull Teacutecnicas habituaispoucos sensiacuteveis paraquadros leves
bull Reflete somente o danoneuronal
bull Teacutecnicas especiaispouca disponibilidade
Caso
bull RM laudo normal
PET-FDG
Vantagens
bull Sensibilidade
bull Reflete dano neuronal
Limitaccedilotildees
bull Custo
bull Sem ponto de corte
bull Natildeo especiacutefico do dano patoloacutegico
Caso
bull PET-FDG hipometabolismo FTP esquerdo e leve a Direita frontal e parietal
bull O que esse laudo mostra
bull Que eu consegui examinar e topografar direito
PET Amiloide
bull Dificuldades Iniciais
bull Marcador a base de Fluor
PET Tau and Amyloid-β Burden in Mild Alzheimers Disease Divergent Relationshipwith Age Cognition and Cerebrospinal Fluid BiomarkersKoychev I1 Gunn RN23 Firouzian A2 Lawson J1 Zamboni G1 Ridha B4 Sahakian BJ5 Rowe JB6 Thomas A7 Rochester L7 Ffytche D8 Howard R9 Zetterberg H9101112 MacKay C1 Lovestone S1 Deep and Frequent Phenotyping study team
J Alzheimers Dis 2017 Aug 8
PET Marcador Amiloacuteide
Vantagens
bull Refletem o processo patoloacutegico
bull Conseguem detectar indiviacuteduos assintomaacuteticos em risco
bull Predizem piora cliacutenica
Limitaccedilotildees
bull Custo
bull Disponibilidade
bull Normalizaccedilatildeo de pontos de corte
Caso
bull PET-Amiloacuteide
241 Estudos
11341 Pacientes
7086 Pacientes
Entatildeo vamos coletar Liacutequor para todos
Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory ClinicPatients in a Prospective CohortHandels RL12 Joore MA23 Vos SJ1 Aalten P1 Ramakers IH1 Rikkert MO4 Scheltens P5 Jansen WJ1 Visser PJ15 van Berckel BM5 van Domburg P6 Smid M7 Hoff E8 Hoogmoed J910 Bouwman F5 Claassen J4 Leentjens AF1 Wolfs CA1 Severens JL11 Verhey FR1Author information
bull 200 DA
bull 16 DA prodromica
bull 69 DFT
bull 59 DCB
bull 16 PSP
bull 44 DCL
bull 22 ACP
bull 41 Demecircncia Semacircntica
bull 52 Afasias logopecircnicas
bull 11 Afasias natildeo fluentes
bull 71 Depressatildeo
bull 49 Queixa subjetiva de memoacuteria
bull DA -100
bull DA prodromica-100
bull 439 dos outros pacientes tbpositivos
bull 818 ACP
bull 788 Afasia logopecircnica
bull 50 DCL
bull 458 DCB
bull 454 afasias natildeo fluentes
bull 366 demecircncia semacircnticas
bull 145 das DFT
bull 117 (Depressatildeo e QSM)
E o teste de Memoacuteria
bull Sensibilidade100
bull Especificidade de 748
bull Intrusotildees Sensibilidade de 83 e Especificidade72
bull 273 tinham deacuteficit hipocampal
bull 366 dos deprimidos
bull 40 DCL
bull 375 PSP
bull 319 DFT
bull 273 Afasia natildeo fluente
bull 227 ACP
bull 22 Demecircncia Semacircntica
bull 22 DCB
bull 58 Afasia logopecircnica
Existiu uma correlaccedilatildeo desempenho com os marcadores
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
bull 74 pacientes com Doenccedila de Alzheimer x 142 com
Comprometimento Cognitivo Leve e 82 controles
bull Hipometabolismo
- Precuneos
- Ciacutengulo Posterior
- Coacutertex Temporo-parietal
- Coacutertex Frontal
Koivunen et al Neurology 2011
bull 29 pacientes acompanhados por 2 anos
bull Avaliaccedilatildeo de PET com PIB e RM (Atrofia de
hipocampo)
bull 1729 converteram
bull Maior depoacutesito de PIB Ciacutengulo Posterior frontal lateral
temporal e putamem com maior atrofia
bull Pouca modificaccedilao no PIB em 2 anos
bull Aumento da atrofia
Hipoacutetese da Evoluccedilatildeo Temporal
dos processos fisiopatoloacutegicos
Biomarcador e CCL
Criteacuterios para Pesquisa DA
Porque utilizar biomarcador empacientes com quadros cognitivos
bull O paciente vai piorar dos sintomas cognitivos
bull Existe um processo patoloacutegico jaacute conhecido
bull Existe dano neuronal Topografia
bull Falsos positivos o que fazer
Ressonacircncia Magneacutetica de Cracircnio
bull Atrofia hipocampal
bull Casos leves ou assintomaacuteticos
bull Avaliaccedilatildeo de espessura cortical (Walhovd K et al 2010)
bull DTI (Sexton C et al 2011)
Ressonacircncia Magneacutetica
Vantagens
bull Disponibilidade
bull Visualizaccedilatildeo de atrofia
bull Possibilidade de vaacuterias mediccedilotildees
Limitaccedilotildees
bull Teacutecnicas habituaispoucos sensiacuteveis paraquadros leves
bull Reflete somente o danoneuronal
bull Teacutecnicas especiaispouca disponibilidade
Caso
bull RM laudo normal
PET-FDG
Vantagens
bull Sensibilidade
bull Reflete dano neuronal
Limitaccedilotildees
bull Custo
bull Sem ponto de corte
bull Natildeo especiacutefico do dano patoloacutegico
Caso
bull PET-FDG hipometabolismo FTP esquerdo e leve a Direita frontal e parietal
bull O que esse laudo mostra
bull Que eu consegui examinar e topografar direito
PET Amiloide
bull Dificuldades Iniciais
bull Marcador a base de Fluor
PET Tau and Amyloid-β Burden in Mild Alzheimers Disease Divergent Relationshipwith Age Cognition and Cerebrospinal Fluid BiomarkersKoychev I1 Gunn RN23 Firouzian A2 Lawson J1 Zamboni G1 Ridha B4 Sahakian BJ5 Rowe JB6 Thomas A7 Rochester L7 Ffytche D8 Howard R9 Zetterberg H9101112 MacKay C1 Lovestone S1 Deep and Frequent Phenotyping study team
J Alzheimers Dis 2017 Aug 8
PET Marcador Amiloacuteide
Vantagens
bull Refletem o processo patoloacutegico
bull Conseguem detectar indiviacuteduos assintomaacuteticos em risco
bull Predizem piora cliacutenica
Limitaccedilotildees
bull Custo
bull Disponibilidade
bull Normalizaccedilatildeo de pontos de corte
Caso
bull PET-Amiloacuteide
241 Estudos
11341 Pacientes
7086 Pacientes
Entatildeo vamos coletar Liacutequor para todos
Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory ClinicPatients in a Prospective CohortHandels RL12 Joore MA23 Vos SJ1 Aalten P1 Ramakers IH1 Rikkert MO4 Scheltens P5 Jansen WJ1 Visser PJ15 van Berckel BM5 van Domburg P6 Smid M7 Hoff E8 Hoogmoed J910 Bouwman F5 Claassen J4 Leentjens AF1 Wolfs CA1 Severens JL11 Verhey FR1Author information
bull 200 DA
bull 16 DA prodromica
bull 69 DFT
bull 59 DCB
bull 16 PSP
bull 44 DCL
bull 22 ACP
bull 41 Demecircncia Semacircntica
bull 52 Afasias logopecircnicas
bull 11 Afasias natildeo fluentes
bull 71 Depressatildeo
bull 49 Queixa subjetiva de memoacuteria
bull DA -100
bull DA prodromica-100
bull 439 dos outros pacientes tbpositivos
bull 818 ACP
bull 788 Afasia logopecircnica
bull 50 DCL
bull 458 DCB
bull 454 afasias natildeo fluentes
bull 366 demecircncia semacircnticas
bull 145 das DFT
bull 117 (Depressatildeo e QSM)
E o teste de Memoacuteria
bull Sensibilidade100
bull Especificidade de 748
bull Intrusotildees Sensibilidade de 83 e Especificidade72
bull 273 tinham deacuteficit hipocampal
bull 366 dos deprimidos
bull 40 DCL
bull 375 PSP
bull 319 DFT
bull 273 Afasia natildeo fluente
bull 227 ACP
bull 22 Demecircncia Semacircntica
bull 22 DCB
bull 58 Afasia logopecircnica
Existiu uma correlaccedilatildeo desempenho com os marcadores
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
Koivunen et al Neurology 2011
bull 29 pacientes acompanhados por 2 anos
bull Avaliaccedilatildeo de PET com PIB e RM (Atrofia de
hipocampo)
bull 1729 converteram
bull Maior depoacutesito de PIB Ciacutengulo Posterior frontal lateral
temporal e putamem com maior atrofia
bull Pouca modificaccedilao no PIB em 2 anos
bull Aumento da atrofia
Hipoacutetese da Evoluccedilatildeo Temporal
dos processos fisiopatoloacutegicos
Biomarcador e CCL
Criteacuterios para Pesquisa DA
Porque utilizar biomarcador empacientes com quadros cognitivos
bull O paciente vai piorar dos sintomas cognitivos
bull Existe um processo patoloacutegico jaacute conhecido
bull Existe dano neuronal Topografia
bull Falsos positivos o que fazer
Ressonacircncia Magneacutetica de Cracircnio
bull Atrofia hipocampal
bull Casos leves ou assintomaacuteticos
bull Avaliaccedilatildeo de espessura cortical (Walhovd K et al 2010)
bull DTI (Sexton C et al 2011)
Ressonacircncia Magneacutetica
Vantagens
bull Disponibilidade
bull Visualizaccedilatildeo de atrofia
bull Possibilidade de vaacuterias mediccedilotildees
Limitaccedilotildees
bull Teacutecnicas habituaispoucos sensiacuteveis paraquadros leves
bull Reflete somente o danoneuronal
bull Teacutecnicas especiaispouca disponibilidade
Caso
bull RM laudo normal
PET-FDG
Vantagens
bull Sensibilidade
bull Reflete dano neuronal
Limitaccedilotildees
bull Custo
bull Sem ponto de corte
bull Natildeo especiacutefico do dano patoloacutegico
Caso
bull PET-FDG hipometabolismo FTP esquerdo e leve a Direita frontal e parietal
bull O que esse laudo mostra
bull Que eu consegui examinar e topografar direito
PET Amiloide
bull Dificuldades Iniciais
bull Marcador a base de Fluor
PET Tau and Amyloid-β Burden in Mild Alzheimers Disease Divergent Relationshipwith Age Cognition and Cerebrospinal Fluid BiomarkersKoychev I1 Gunn RN23 Firouzian A2 Lawson J1 Zamboni G1 Ridha B4 Sahakian BJ5 Rowe JB6 Thomas A7 Rochester L7 Ffytche D8 Howard R9 Zetterberg H9101112 MacKay C1 Lovestone S1 Deep and Frequent Phenotyping study team
J Alzheimers Dis 2017 Aug 8
PET Marcador Amiloacuteide
Vantagens
bull Refletem o processo patoloacutegico
bull Conseguem detectar indiviacuteduos assintomaacuteticos em risco
bull Predizem piora cliacutenica
Limitaccedilotildees
bull Custo
bull Disponibilidade
bull Normalizaccedilatildeo de pontos de corte
Caso
bull PET-Amiloacuteide
241 Estudos
11341 Pacientes
7086 Pacientes
Entatildeo vamos coletar Liacutequor para todos
Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory ClinicPatients in a Prospective CohortHandels RL12 Joore MA23 Vos SJ1 Aalten P1 Ramakers IH1 Rikkert MO4 Scheltens P5 Jansen WJ1 Visser PJ15 van Berckel BM5 van Domburg P6 Smid M7 Hoff E8 Hoogmoed J910 Bouwman F5 Claassen J4 Leentjens AF1 Wolfs CA1 Severens JL11 Verhey FR1Author information
bull 200 DA
bull 16 DA prodromica
bull 69 DFT
bull 59 DCB
bull 16 PSP
bull 44 DCL
bull 22 ACP
bull 41 Demecircncia Semacircntica
bull 52 Afasias logopecircnicas
bull 11 Afasias natildeo fluentes
bull 71 Depressatildeo
bull 49 Queixa subjetiva de memoacuteria
bull DA -100
bull DA prodromica-100
bull 439 dos outros pacientes tbpositivos
bull 818 ACP
bull 788 Afasia logopecircnica
bull 50 DCL
bull 458 DCB
bull 454 afasias natildeo fluentes
bull 366 demecircncia semacircnticas
bull 145 das DFT
bull 117 (Depressatildeo e QSM)
E o teste de Memoacuteria
bull Sensibilidade100
bull Especificidade de 748
bull Intrusotildees Sensibilidade de 83 e Especificidade72
bull 273 tinham deacuteficit hipocampal
bull 366 dos deprimidos
bull 40 DCL
bull 375 PSP
bull 319 DFT
bull 273 Afasia natildeo fluente
bull 227 ACP
bull 22 Demecircncia Semacircntica
bull 22 DCB
bull 58 Afasia logopecircnica
Existiu uma correlaccedilatildeo desempenho com os marcadores
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
Hipoacutetese da Evoluccedilatildeo Temporal
dos processos fisiopatoloacutegicos
Biomarcador e CCL
Criteacuterios para Pesquisa DA
Porque utilizar biomarcador empacientes com quadros cognitivos
bull O paciente vai piorar dos sintomas cognitivos
bull Existe um processo patoloacutegico jaacute conhecido
bull Existe dano neuronal Topografia
bull Falsos positivos o que fazer
Ressonacircncia Magneacutetica de Cracircnio
bull Atrofia hipocampal
bull Casos leves ou assintomaacuteticos
bull Avaliaccedilatildeo de espessura cortical (Walhovd K et al 2010)
bull DTI (Sexton C et al 2011)
Ressonacircncia Magneacutetica
Vantagens
bull Disponibilidade
bull Visualizaccedilatildeo de atrofia
bull Possibilidade de vaacuterias mediccedilotildees
Limitaccedilotildees
bull Teacutecnicas habituaispoucos sensiacuteveis paraquadros leves
bull Reflete somente o danoneuronal
bull Teacutecnicas especiaispouca disponibilidade
Caso
bull RM laudo normal
PET-FDG
Vantagens
bull Sensibilidade
bull Reflete dano neuronal
Limitaccedilotildees
bull Custo
bull Sem ponto de corte
bull Natildeo especiacutefico do dano patoloacutegico
Caso
bull PET-FDG hipometabolismo FTP esquerdo e leve a Direita frontal e parietal
bull O que esse laudo mostra
bull Que eu consegui examinar e topografar direito
PET Amiloide
bull Dificuldades Iniciais
bull Marcador a base de Fluor
PET Tau and Amyloid-β Burden in Mild Alzheimers Disease Divergent Relationshipwith Age Cognition and Cerebrospinal Fluid BiomarkersKoychev I1 Gunn RN23 Firouzian A2 Lawson J1 Zamboni G1 Ridha B4 Sahakian BJ5 Rowe JB6 Thomas A7 Rochester L7 Ffytche D8 Howard R9 Zetterberg H9101112 MacKay C1 Lovestone S1 Deep and Frequent Phenotyping study team
J Alzheimers Dis 2017 Aug 8
PET Marcador Amiloacuteide
Vantagens
bull Refletem o processo patoloacutegico
bull Conseguem detectar indiviacuteduos assintomaacuteticos em risco
bull Predizem piora cliacutenica
Limitaccedilotildees
bull Custo
bull Disponibilidade
bull Normalizaccedilatildeo de pontos de corte
Caso
bull PET-Amiloacuteide
241 Estudos
11341 Pacientes
7086 Pacientes
Entatildeo vamos coletar Liacutequor para todos
Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory ClinicPatients in a Prospective CohortHandels RL12 Joore MA23 Vos SJ1 Aalten P1 Ramakers IH1 Rikkert MO4 Scheltens P5 Jansen WJ1 Visser PJ15 van Berckel BM5 van Domburg P6 Smid M7 Hoff E8 Hoogmoed J910 Bouwman F5 Claassen J4 Leentjens AF1 Wolfs CA1 Severens JL11 Verhey FR1Author information
bull 200 DA
bull 16 DA prodromica
bull 69 DFT
bull 59 DCB
bull 16 PSP
bull 44 DCL
bull 22 ACP
bull 41 Demecircncia Semacircntica
bull 52 Afasias logopecircnicas
bull 11 Afasias natildeo fluentes
bull 71 Depressatildeo
bull 49 Queixa subjetiva de memoacuteria
bull DA -100
bull DA prodromica-100
bull 439 dos outros pacientes tbpositivos
bull 818 ACP
bull 788 Afasia logopecircnica
bull 50 DCL
bull 458 DCB
bull 454 afasias natildeo fluentes
bull 366 demecircncia semacircnticas
bull 145 das DFT
bull 117 (Depressatildeo e QSM)
E o teste de Memoacuteria
bull Sensibilidade100
bull Especificidade de 748
bull Intrusotildees Sensibilidade de 83 e Especificidade72
bull 273 tinham deacuteficit hipocampal
bull 366 dos deprimidos
bull 40 DCL
bull 375 PSP
bull 319 DFT
bull 273 Afasia natildeo fluente
bull 227 ACP
bull 22 Demecircncia Semacircntica
bull 22 DCB
bull 58 Afasia logopecircnica
Existiu uma correlaccedilatildeo desempenho com os marcadores
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
Biomarcador e CCL
Criteacuterios para Pesquisa DA
Porque utilizar biomarcador empacientes com quadros cognitivos
bull O paciente vai piorar dos sintomas cognitivos
bull Existe um processo patoloacutegico jaacute conhecido
bull Existe dano neuronal Topografia
bull Falsos positivos o que fazer
Ressonacircncia Magneacutetica de Cracircnio
bull Atrofia hipocampal
bull Casos leves ou assintomaacuteticos
bull Avaliaccedilatildeo de espessura cortical (Walhovd K et al 2010)
bull DTI (Sexton C et al 2011)
Ressonacircncia Magneacutetica
Vantagens
bull Disponibilidade
bull Visualizaccedilatildeo de atrofia
bull Possibilidade de vaacuterias mediccedilotildees
Limitaccedilotildees
bull Teacutecnicas habituaispoucos sensiacuteveis paraquadros leves
bull Reflete somente o danoneuronal
bull Teacutecnicas especiaispouca disponibilidade
Caso
bull RM laudo normal
PET-FDG
Vantagens
bull Sensibilidade
bull Reflete dano neuronal
Limitaccedilotildees
bull Custo
bull Sem ponto de corte
bull Natildeo especiacutefico do dano patoloacutegico
Caso
bull PET-FDG hipometabolismo FTP esquerdo e leve a Direita frontal e parietal
bull O que esse laudo mostra
bull Que eu consegui examinar e topografar direito
PET Amiloide
bull Dificuldades Iniciais
bull Marcador a base de Fluor
PET Tau and Amyloid-β Burden in Mild Alzheimers Disease Divergent Relationshipwith Age Cognition and Cerebrospinal Fluid BiomarkersKoychev I1 Gunn RN23 Firouzian A2 Lawson J1 Zamboni G1 Ridha B4 Sahakian BJ5 Rowe JB6 Thomas A7 Rochester L7 Ffytche D8 Howard R9 Zetterberg H9101112 MacKay C1 Lovestone S1 Deep and Frequent Phenotyping study team
J Alzheimers Dis 2017 Aug 8
PET Marcador Amiloacuteide
Vantagens
bull Refletem o processo patoloacutegico
bull Conseguem detectar indiviacuteduos assintomaacuteticos em risco
bull Predizem piora cliacutenica
Limitaccedilotildees
bull Custo
bull Disponibilidade
bull Normalizaccedilatildeo de pontos de corte
Caso
bull PET-Amiloacuteide
241 Estudos
11341 Pacientes
7086 Pacientes
Entatildeo vamos coletar Liacutequor para todos
Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory ClinicPatients in a Prospective CohortHandels RL12 Joore MA23 Vos SJ1 Aalten P1 Ramakers IH1 Rikkert MO4 Scheltens P5 Jansen WJ1 Visser PJ15 van Berckel BM5 van Domburg P6 Smid M7 Hoff E8 Hoogmoed J910 Bouwman F5 Claassen J4 Leentjens AF1 Wolfs CA1 Severens JL11 Verhey FR1Author information
bull 200 DA
bull 16 DA prodromica
bull 69 DFT
bull 59 DCB
bull 16 PSP
bull 44 DCL
bull 22 ACP
bull 41 Demecircncia Semacircntica
bull 52 Afasias logopecircnicas
bull 11 Afasias natildeo fluentes
bull 71 Depressatildeo
bull 49 Queixa subjetiva de memoacuteria
bull DA -100
bull DA prodromica-100
bull 439 dos outros pacientes tbpositivos
bull 818 ACP
bull 788 Afasia logopecircnica
bull 50 DCL
bull 458 DCB
bull 454 afasias natildeo fluentes
bull 366 demecircncia semacircnticas
bull 145 das DFT
bull 117 (Depressatildeo e QSM)
E o teste de Memoacuteria
bull Sensibilidade100
bull Especificidade de 748
bull Intrusotildees Sensibilidade de 83 e Especificidade72
bull 273 tinham deacuteficit hipocampal
bull 366 dos deprimidos
bull 40 DCL
bull 375 PSP
bull 319 DFT
bull 273 Afasia natildeo fluente
bull 227 ACP
bull 22 Demecircncia Semacircntica
bull 22 DCB
bull 58 Afasia logopecircnica
Existiu uma correlaccedilatildeo desempenho com os marcadores
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
Criteacuterios para Pesquisa DA
Porque utilizar biomarcador empacientes com quadros cognitivos
bull O paciente vai piorar dos sintomas cognitivos
bull Existe um processo patoloacutegico jaacute conhecido
bull Existe dano neuronal Topografia
bull Falsos positivos o que fazer
Ressonacircncia Magneacutetica de Cracircnio
bull Atrofia hipocampal
bull Casos leves ou assintomaacuteticos
bull Avaliaccedilatildeo de espessura cortical (Walhovd K et al 2010)
bull DTI (Sexton C et al 2011)
Ressonacircncia Magneacutetica
Vantagens
bull Disponibilidade
bull Visualizaccedilatildeo de atrofia
bull Possibilidade de vaacuterias mediccedilotildees
Limitaccedilotildees
bull Teacutecnicas habituaispoucos sensiacuteveis paraquadros leves
bull Reflete somente o danoneuronal
bull Teacutecnicas especiaispouca disponibilidade
Caso
bull RM laudo normal
PET-FDG
Vantagens
bull Sensibilidade
bull Reflete dano neuronal
Limitaccedilotildees
bull Custo
bull Sem ponto de corte
bull Natildeo especiacutefico do dano patoloacutegico
Caso
bull PET-FDG hipometabolismo FTP esquerdo e leve a Direita frontal e parietal
bull O que esse laudo mostra
bull Que eu consegui examinar e topografar direito
PET Amiloide
bull Dificuldades Iniciais
bull Marcador a base de Fluor
PET Tau and Amyloid-β Burden in Mild Alzheimers Disease Divergent Relationshipwith Age Cognition and Cerebrospinal Fluid BiomarkersKoychev I1 Gunn RN23 Firouzian A2 Lawson J1 Zamboni G1 Ridha B4 Sahakian BJ5 Rowe JB6 Thomas A7 Rochester L7 Ffytche D8 Howard R9 Zetterberg H9101112 MacKay C1 Lovestone S1 Deep and Frequent Phenotyping study team
J Alzheimers Dis 2017 Aug 8
PET Marcador Amiloacuteide
Vantagens
bull Refletem o processo patoloacutegico
bull Conseguem detectar indiviacuteduos assintomaacuteticos em risco
bull Predizem piora cliacutenica
Limitaccedilotildees
bull Custo
bull Disponibilidade
bull Normalizaccedilatildeo de pontos de corte
Caso
bull PET-Amiloacuteide
241 Estudos
11341 Pacientes
7086 Pacientes
Entatildeo vamos coletar Liacutequor para todos
Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory ClinicPatients in a Prospective CohortHandels RL12 Joore MA23 Vos SJ1 Aalten P1 Ramakers IH1 Rikkert MO4 Scheltens P5 Jansen WJ1 Visser PJ15 van Berckel BM5 van Domburg P6 Smid M7 Hoff E8 Hoogmoed J910 Bouwman F5 Claassen J4 Leentjens AF1 Wolfs CA1 Severens JL11 Verhey FR1Author information
bull 200 DA
bull 16 DA prodromica
bull 69 DFT
bull 59 DCB
bull 16 PSP
bull 44 DCL
bull 22 ACP
bull 41 Demecircncia Semacircntica
bull 52 Afasias logopecircnicas
bull 11 Afasias natildeo fluentes
bull 71 Depressatildeo
bull 49 Queixa subjetiva de memoacuteria
bull DA -100
bull DA prodromica-100
bull 439 dos outros pacientes tbpositivos
bull 818 ACP
bull 788 Afasia logopecircnica
bull 50 DCL
bull 458 DCB
bull 454 afasias natildeo fluentes
bull 366 demecircncia semacircnticas
bull 145 das DFT
bull 117 (Depressatildeo e QSM)
E o teste de Memoacuteria
bull Sensibilidade100
bull Especificidade de 748
bull Intrusotildees Sensibilidade de 83 e Especificidade72
bull 273 tinham deacuteficit hipocampal
bull 366 dos deprimidos
bull 40 DCL
bull 375 PSP
bull 319 DFT
bull 273 Afasia natildeo fluente
bull 227 ACP
bull 22 Demecircncia Semacircntica
bull 22 DCB
bull 58 Afasia logopecircnica
Existiu uma correlaccedilatildeo desempenho com os marcadores
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
Porque utilizar biomarcador empacientes com quadros cognitivos
bull O paciente vai piorar dos sintomas cognitivos
bull Existe um processo patoloacutegico jaacute conhecido
bull Existe dano neuronal Topografia
bull Falsos positivos o que fazer
Ressonacircncia Magneacutetica de Cracircnio
bull Atrofia hipocampal
bull Casos leves ou assintomaacuteticos
bull Avaliaccedilatildeo de espessura cortical (Walhovd K et al 2010)
bull DTI (Sexton C et al 2011)
Ressonacircncia Magneacutetica
Vantagens
bull Disponibilidade
bull Visualizaccedilatildeo de atrofia
bull Possibilidade de vaacuterias mediccedilotildees
Limitaccedilotildees
bull Teacutecnicas habituaispoucos sensiacuteveis paraquadros leves
bull Reflete somente o danoneuronal
bull Teacutecnicas especiaispouca disponibilidade
Caso
bull RM laudo normal
PET-FDG
Vantagens
bull Sensibilidade
bull Reflete dano neuronal
Limitaccedilotildees
bull Custo
bull Sem ponto de corte
bull Natildeo especiacutefico do dano patoloacutegico
Caso
bull PET-FDG hipometabolismo FTP esquerdo e leve a Direita frontal e parietal
bull O que esse laudo mostra
bull Que eu consegui examinar e topografar direito
PET Amiloide
bull Dificuldades Iniciais
bull Marcador a base de Fluor
PET Tau and Amyloid-β Burden in Mild Alzheimers Disease Divergent Relationshipwith Age Cognition and Cerebrospinal Fluid BiomarkersKoychev I1 Gunn RN23 Firouzian A2 Lawson J1 Zamboni G1 Ridha B4 Sahakian BJ5 Rowe JB6 Thomas A7 Rochester L7 Ffytche D8 Howard R9 Zetterberg H9101112 MacKay C1 Lovestone S1 Deep and Frequent Phenotyping study team
J Alzheimers Dis 2017 Aug 8
PET Marcador Amiloacuteide
Vantagens
bull Refletem o processo patoloacutegico
bull Conseguem detectar indiviacuteduos assintomaacuteticos em risco
bull Predizem piora cliacutenica
Limitaccedilotildees
bull Custo
bull Disponibilidade
bull Normalizaccedilatildeo de pontos de corte
Caso
bull PET-Amiloacuteide
241 Estudos
11341 Pacientes
7086 Pacientes
Entatildeo vamos coletar Liacutequor para todos
Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory ClinicPatients in a Prospective CohortHandels RL12 Joore MA23 Vos SJ1 Aalten P1 Ramakers IH1 Rikkert MO4 Scheltens P5 Jansen WJ1 Visser PJ15 van Berckel BM5 van Domburg P6 Smid M7 Hoff E8 Hoogmoed J910 Bouwman F5 Claassen J4 Leentjens AF1 Wolfs CA1 Severens JL11 Verhey FR1Author information
bull 200 DA
bull 16 DA prodromica
bull 69 DFT
bull 59 DCB
bull 16 PSP
bull 44 DCL
bull 22 ACP
bull 41 Demecircncia Semacircntica
bull 52 Afasias logopecircnicas
bull 11 Afasias natildeo fluentes
bull 71 Depressatildeo
bull 49 Queixa subjetiva de memoacuteria
bull DA -100
bull DA prodromica-100
bull 439 dos outros pacientes tbpositivos
bull 818 ACP
bull 788 Afasia logopecircnica
bull 50 DCL
bull 458 DCB
bull 454 afasias natildeo fluentes
bull 366 demecircncia semacircnticas
bull 145 das DFT
bull 117 (Depressatildeo e QSM)
E o teste de Memoacuteria
bull Sensibilidade100
bull Especificidade de 748
bull Intrusotildees Sensibilidade de 83 e Especificidade72
bull 273 tinham deacuteficit hipocampal
bull 366 dos deprimidos
bull 40 DCL
bull 375 PSP
bull 319 DFT
bull 273 Afasia natildeo fluente
bull 227 ACP
bull 22 Demecircncia Semacircntica
bull 22 DCB
bull 58 Afasia logopecircnica
Existiu uma correlaccedilatildeo desempenho com os marcadores
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
Ressonacircncia Magneacutetica de Cracircnio
bull Atrofia hipocampal
bull Casos leves ou assintomaacuteticos
bull Avaliaccedilatildeo de espessura cortical (Walhovd K et al 2010)
bull DTI (Sexton C et al 2011)
Ressonacircncia Magneacutetica
Vantagens
bull Disponibilidade
bull Visualizaccedilatildeo de atrofia
bull Possibilidade de vaacuterias mediccedilotildees
Limitaccedilotildees
bull Teacutecnicas habituaispoucos sensiacuteveis paraquadros leves
bull Reflete somente o danoneuronal
bull Teacutecnicas especiaispouca disponibilidade
Caso
bull RM laudo normal
PET-FDG
Vantagens
bull Sensibilidade
bull Reflete dano neuronal
Limitaccedilotildees
bull Custo
bull Sem ponto de corte
bull Natildeo especiacutefico do dano patoloacutegico
Caso
bull PET-FDG hipometabolismo FTP esquerdo e leve a Direita frontal e parietal
bull O que esse laudo mostra
bull Que eu consegui examinar e topografar direito
PET Amiloide
bull Dificuldades Iniciais
bull Marcador a base de Fluor
PET Tau and Amyloid-β Burden in Mild Alzheimers Disease Divergent Relationshipwith Age Cognition and Cerebrospinal Fluid BiomarkersKoychev I1 Gunn RN23 Firouzian A2 Lawson J1 Zamboni G1 Ridha B4 Sahakian BJ5 Rowe JB6 Thomas A7 Rochester L7 Ffytche D8 Howard R9 Zetterberg H9101112 MacKay C1 Lovestone S1 Deep and Frequent Phenotyping study team
J Alzheimers Dis 2017 Aug 8
PET Marcador Amiloacuteide
Vantagens
bull Refletem o processo patoloacutegico
bull Conseguem detectar indiviacuteduos assintomaacuteticos em risco
bull Predizem piora cliacutenica
Limitaccedilotildees
bull Custo
bull Disponibilidade
bull Normalizaccedilatildeo de pontos de corte
Caso
bull PET-Amiloacuteide
241 Estudos
11341 Pacientes
7086 Pacientes
Entatildeo vamos coletar Liacutequor para todos
Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory ClinicPatients in a Prospective CohortHandels RL12 Joore MA23 Vos SJ1 Aalten P1 Ramakers IH1 Rikkert MO4 Scheltens P5 Jansen WJ1 Visser PJ15 van Berckel BM5 van Domburg P6 Smid M7 Hoff E8 Hoogmoed J910 Bouwman F5 Claassen J4 Leentjens AF1 Wolfs CA1 Severens JL11 Verhey FR1Author information
bull 200 DA
bull 16 DA prodromica
bull 69 DFT
bull 59 DCB
bull 16 PSP
bull 44 DCL
bull 22 ACP
bull 41 Demecircncia Semacircntica
bull 52 Afasias logopecircnicas
bull 11 Afasias natildeo fluentes
bull 71 Depressatildeo
bull 49 Queixa subjetiva de memoacuteria
bull DA -100
bull DA prodromica-100
bull 439 dos outros pacientes tbpositivos
bull 818 ACP
bull 788 Afasia logopecircnica
bull 50 DCL
bull 458 DCB
bull 454 afasias natildeo fluentes
bull 366 demecircncia semacircnticas
bull 145 das DFT
bull 117 (Depressatildeo e QSM)
E o teste de Memoacuteria
bull Sensibilidade100
bull Especificidade de 748
bull Intrusotildees Sensibilidade de 83 e Especificidade72
bull 273 tinham deacuteficit hipocampal
bull 366 dos deprimidos
bull 40 DCL
bull 375 PSP
bull 319 DFT
bull 273 Afasia natildeo fluente
bull 227 ACP
bull 22 Demecircncia Semacircntica
bull 22 DCB
bull 58 Afasia logopecircnica
Existiu uma correlaccedilatildeo desempenho com os marcadores
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
Ressonacircncia Magneacutetica
Vantagens
bull Disponibilidade
bull Visualizaccedilatildeo de atrofia
bull Possibilidade de vaacuterias mediccedilotildees
Limitaccedilotildees
bull Teacutecnicas habituaispoucos sensiacuteveis paraquadros leves
bull Reflete somente o danoneuronal
bull Teacutecnicas especiaispouca disponibilidade
Caso
bull RM laudo normal
PET-FDG
Vantagens
bull Sensibilidade
bull Reflete dano neuronal
Limitaccedilotildees
bull Custo
bull Sem ponto de corte
bull Natildeo especiacutefico do dano patoloacutegico
Caso
bull PET-FDG hipometabolismo FTP esquerdo e leve a Direita frontal e parietal
bull O que esse laudo mostra
bull Que eu consegui examinar e topografar direito
PET Amiloide
bull Dificuldades Iniciais
bull Marcador a base de Fluor
PET Tau and Amyloid-β Burden in Mild Alzheimers Disease Divergent Relationshipwith Age Cognition and Cerebrospinal Fluid BiomarkersKoychev I1 Gunn RN23 Firouzian A2 Lawson J1 Zamboni G1 Ridha B4 Sahakian BJ5 Rowe JB6 Thomas A7 Rochester L7 Ffytche D8 Howard R9 Zetterberg H9101112 MacKay C1 Lovestone S1 Deep and Frequent Phenotyping study team
J Alzheimers Dis 2017 Aug 8
PET Marcador Amiloacuteide
Vantagens
bull Refletem o processo patoloacutegico
bull Conseguem detectar indiviacuteduos assintomaacuteticos em risco
bull Predizem piora cliacutenica
Limitaccedilotildees
bull Custo
bull Disponibilidade
bull Normalizaccedilatildeo de pontos de corte
Caso
bull PET-Amiloacuteide
241 Estudos
11341 Pacientes
7086 Pacientes
Entatildeo vamos coletar Liacutequor para todos
Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory ClinicPatients in a Prospective CohortHandels RL12 Joore MA23 Vos SJ1 Aalten P1 Ramakers IH1 Rikkert MO4 Scheltens P5 Jansen WJ1 Visser PJ15 van Berckel BM5 van Domburg P6 Smid M7 Hoff E8 Hoogmoed J910 Bouwman F5 Claassen J4 Leentjens AF1 Wolfs CA1 Severens JL11 Verhey FR1Author information
bull 200 DA
bull 16 DA prodromica
bull 69 DFT
bull 59 DCB
bull 16 PSP
bull 44 DCL
bull 22 ACP
bull 41 Demecircncia Semacircntica
bull 52 Afasias logopecircnicas
bull 11 Afasias natildeo fluentes
bull 71 Depressatildeo
bull 49 Queixa subjetiva de memoacuteria
bull DA -100
bull DA prodromica-100
bull 439 dos outros pacientes tbpositivos
bull 818 ACP
bull 788 Afasia logopecircnica
bull 50 DCL
bull 458 DCB
bull 454 afasias natildeo fluentes
bull 366 demecircncia semacircnticas
bull 145 das DFT
bull 117 (Depressatildeo e QSM)
E o teste de Memoacuteria
bull Sensibilidade100
bull Especificidade de 748
bull Intrusotildees Sensibilidade de 83 e Especificidade72
bull 273 tinham deacuteficit hipocampal
bull 366 dos deprimidos
bull 40 DCL
bull 375 PSP
bull 319 DFT
bull 273 Afasia natildeo fluente
bull 227 ACP
bull 22 Demecircncia Semacircntica
bull 22 DCB
bull 58 Afasia logopecircnica
Existiu uma correlaccedilatildeo desempenho com os marcadores
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
Caso
bull RM laudo normal
PET-FDG
Vantagens
bull Sensibilidade
bull Reflete dano neuronal
Limitaccedilotildees
bull Custo
bull Sem ponto de corte
bull Natildeo especiacutefico do dano patoloacutegico
Caso
bull PET-FDG hipometabolismo FTP esquerdo e leve a Direita frontal e parietal
bull O que esse laudo mostra
bull Que eu consegui examinar e topografar direito
PET Amiloide
bull Dificuldades Iniciais
bull Marcador a base de Fluor
PET Tau and Amyloid-β Burden in Mild Alzheimers Disease Divergent Relationshipwith Age Cognition and Cerebrospinal Fluid BiomarkersKoychev I1 Gunn RN23 Firouzian A2 Lawson J1 Zamboni G1 Ridha B4 Sahakian BJ5 Rowe JB6 Thomas A7 Rochester L7 Ffytche D8 Howard R9 Zetterberg H9101112 MacKay C1 Lovestone S1 Deep and Frequent Phenotyping study team
J Alzheimers Dis 2017 Aug 8
PET Marcador Amiloacuteide
Vantagens
bull Refletem o processo patoloacutegico
bull Conseguem detectar indiviacuteduos assintomaacuteticos em risco
bull Predizem piora cliacutenica
Limitaccedilotildees
bull Custo
bull Disponibilidade
bull Normalizaccedilatildeo de pontos de corte
Caso
bull PET-Amiloacuteide
241 Estudos
11341 Pacientes
7086 Pacientes
Entatildeo vamos coletar Liacutequor para todos
Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory ClinicPatients in a Prospective CohortHandels RL12 Joore MA23 Vos SJ1 Aalten P1 Ramakers IH1 Rikkert MO4 Scheltens P5 Jansen WJ1 Visser PJ15 van Berckel BM5 van Domburg P6 Smid M7 Hoff E8 Hoogmoed J910 Bouwman F5 Claassen J4 Leentjens AF1 Wolfs CA1 Severens JL11 Verhey FR1Author information
bull 200 DA
bull 16 DA prodromica
bull 69 DFT
bull 59 DCB
bull 16 PSP
bull 44 DCL
bull 22 ACP
bull 41 Demecircncia Semacircntica
bull 52 Afasias logopecircnicas
bull 11 Afasias natildeo fluentes
bull 71 Depressatildeo
bull 49 Queixa subjetiva de memoacuteria
bull DA -100
bull DA prodromica-100
bull 439 dos outros pacientes tbpositivos
bull 818 ACP
bull 788 Afasia logopecircnica
bull 50 DCL
bull 458 DCB
bull 454 afasias natildeo fluentes
bull 366 demecircncia semacircnticas
bull 145 das DFT
bull 117 (Depressatildeo e QSM)
E o teste de Memoacuteria
bull Sensibilidade100
bull Especificidade de 748
bull Intrusotildees Sensibilidade de 83 e Especificidade72
bull 273 tinham deacuteficit hipocampal
bull 366 dos deprimidos
bull 40 DCL
bull 375 PSP
bull 319 DFT
bull 273 Afasia natildeo fluente
bull 227 ACP
bull 22 Demecircncia Semacircntica
bull 22 DCB
bull 58 Afasia logopecircnica
Existiu uma correlaccedilatildeo desempenho com os marcadores
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
PET-FDG
Vantagens
bull Sensibilidade
bull Reflete dano neuronal
Limitaccedilotildees
bull Custo
bull Sem ponto de corte
bull Natildeo especiacutefico do dano patoloacutegico
Caso
bull PET-FDG hipometabolismo FTP esquerdo e leve a Direita frontal e parietal
bull O que esse laudo mostra
bull Que eu consegui examinar e topografar direito
PET Amiloide
bull Dificuldades Iniciais
bull Marcador a base de Fluor
PET Tau and Amyloid-β Burden in Mild Alzheimers Disease Divergent Relationshipwith Age Cognition and Cerebrospinal Fluid BiomarkersKoychev I1 Gunn RN23 Firouzian A2 Lawson J1 Zamboni G1 Ridha B4 Sahakian BJ5 Rowe JB6 Thomas A7 Rochester L7 Ffytche D8 Howard R9 Zetterberg H9101112 MacKay C1 Lovestone S1 Deep and Frequent Phenotyping study team
J Alzheimers Dis 2017 Aug 8
PET Marcador Amiloacuteide
Vantagens
bull Refletem o processo patoloacutegico
bull Conseguem detectar indiviacuteduos assintomaacuteticos em risco
bull Predizem piora cliacutenica
Limitaccedilotildees
bull Custo
bull Disponibilidade
bull Normalizaccedilatildeo de pontos de corte
Caso
bull PET-Amiloacuteide
241 Estudos
11341 Pacientes
7086 Pacientes
Entatildeo vamos coletar Liacutequor para todos
Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory ClinicPatients in a Prospective CohortHandels RL12 Joore MA23 Vos SJ1 Aalten P1 Ramakers IH1 Rikkert MO4 Scheltens P5 Jansen WJ1 Visser PJ15 van Berckel BM5 van Domburg P6 Smid M7 Hoff E8 Hoogmoed J910 Bouwman F5 Claassen J4 Leentjens AF1 Wolfs CA1 Severens JL11 Verhey FR1Author information
bull 200 DA
bull 16 DA prodromica
bull 69 DFT
bull 59 DCB
bull 16 PSP
bull 44 DCL
bull 22 ACP
bull 41 Demecircncia Semacircntica
bull 52 Afasias logopecircnicas
bull 11 Afasias natildeo fluentes
bull 71 Depressatildeo
bull 49 Queixa subjetiva de memoacuteria
bull DA -100
bull DA prodromica-100
bull 439 dos outros pacientes tbpositivos
bull 818 ACP
bull 788 Afasia logopecircnica
bull 50 DCL
bull 458 DCB
bull 454 afasias natildeo fluentes
bull 366 demecircncia semacircnticas
bull 145 das DFT
bull 117 (Depressatildeo e QSM)
E o teste de Memoacuteria
bull Sensibilidade100
bull Especificidade de 748
bull Intrusotildees Sensibilidade de 83 e Especificidade72
bull 273 tinham deacuteficit hipocampal
bull 366 dos deprimidos
bull 40 DCL
bull 375 PSP
bull 319 DFT
bull 273 Afasia natildeo fluente
bull 227 ACP
bull 22 Demecircncia Semacircntica
bull 22 DCB
bull 58 Afasia logopecircnica
Existiu uma correlaccedilatildeo desempenho com os marcadores
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
Caso
bull PET-FDG hipometabolismo FTP esquerdo e leve a Direita frontal e parietal
bull O que esse laudo mostra
bull Que eu consegui examinar e topografar direito
PET Amiloide
bull Dificuldades Iniciais
bull Marcador a base de Fluor
PET Tau and Amyloid-β Burden in Mild Alzheimers Disease Divergent Relationshipwith Age Cognition and Cerebrospinal Fluid BiomarkersKoychev I1 Gunn RN23 Firouzian A2 Lawson J1 Zamboni G1 Ridha B4 Sahakian BJ5 Rowe JB6 Thomas A7 Rochester L7 Ffytche D8 Howard R9 Zetterberg H9101112 MacKay C1 Lovestone S1 Deep and Frequent Phenotyping study team
J Alzheimers Dis 2017 Aug 8
PET Marcador Amiloacuteide
Vantagens
bull Refletem o processo patoloacutegico
bull Conseguem detectar indiviacuteduos assintomaacuteticos em risco
bull Predizem piora cliacutenica
Limitaccedilotildees
bull Custo
bull Disponibilidade
bull Normalizaccedilatildeo de pontos de corte
Caso
bull PET-Amiloacuteide
241 Estudos
11341 Pacientes
7086 Pacientes
Entatildeo vamos coletar Liacutequor para todos
Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory ClinicPatients in a Prospective CohortHandels RL12 Joore MA23 Vos SJ1 Aalten P1 Ramakers IH1 Rikkert MO4 Scheltens P5 Jansen WJ1 Visser PJ15 van Berckel BM5 van Domburg P6 Smid M7 Hoff E8 Hoogmoed J910 Bouwman F5 Claassen J4 Leentjens AF1 Wolfs CA1 Severens JL11 Verhey FR1Author information
bull 200 DA
bull 16 DA prodromica
bull 69 DFT
bull 59 DCB
bull 16 PSP
bull 44 DCL
bull 22 ACP
bull 41 Demecircncia Semacircntica
bull 52 Afasias logopecircnicas
bull 11 Afasias natildeo fluentes
bull 71 Depressatildeo
bull 49 Queixa subjetiva de memoacuteria
bull DA -100
bull DA prodromica-100
bull 439 dos outros pacientes tbpositivos
bull 818 ACP
bull 788 Afasia logopecircnica
bull 50 DCL
bull 458 DCB
bull 454 afasias natildeo fluentes
bull 366 demecircncia semacircnticas
bull 145 das DFT
bull 117 (Depressatildeo e QSM)
E o teste de Memoacuteria
bull Sensibilidade100
bull Especificidade de 748
bull Intrusotildees Sensibilidade de 83 e Especificidade72
bull 273 tinham deacuteficit hipocampal
bull 366 dos deprimidos
bull 40 DCL
bull 375 PSP
bull 319 DFT
bull 273 Afasia natildeo fluente
bull 227 ACP
bull 22 Demecircncia Semacircntica
bull 22 DCB
bull 58 Afasia logopecircnica
Existiu uma correlaccedilatildeo desempenho com os marcadores
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
PET Amiloide
bull Dificuldades Iniciais
bull Marcador a base de Fluor
PET Tau and Amyloid-β Burden in Mild Alzheimers Disease Divergent Relationshipwith Age Cognition and Cerebrospinal Fluid BiomarkersKoychev I1 Gunn RN23 Firouzian A2 Lawson J1 Zamboni G1 Ridha B4 Sahakian BJ5 Rowe JB6 Thomas A7 Rochester L7 Ffytche D8 Howard R9 Zetterberg H9101112 MacKay C1 Lovestone S1 Deep and Frequent Phenotyping study team
J Alzheimers Dis 2017 Aug 8
PET Marcador Amiloacuteide
Vantagens
bull Refletem o processo patoloacutegico
bull Conseguem detectar indiviacuteduos assintomaacuteticos em risco
bull Predizem piora cliacutenica
Limitaccedilotildees
bull Custo
bull Disponibilidade
bull Normalizaccedilatildeo de pontos de corte
Caso
bull PET-Amiloacuteide
241 Estudos
11341 Pacientes
7086 Pacientes
Entatildeo vamos coletar Liacutequor para todos
Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory ClinicPatients in a Prospective CohortHandels RL12 Joore MA23 Vos SJ1 Aalten P1 Ramakers IH1 Rikkert MO4 Scheltens P5 Jansen WJ1 Visser PJ15 van Berckel BM5 van Domburg P6 Smid M7 Hoff E8 Hoogmoed J910 Bouwman F5 Claassen J4 Leentjens AF1 Wolfs CA1 Severens JL11 Verhey FR1Author information
bull 200 DA
bull 16 DA prodromica
bull 69 DFT
bull 59 DCB
bull 16 PSP
bull 44 DCL
bull 22 ACP
bull 41 Demecircncia Semacircntica
bull 52 Afasias logopecircnicas
bull 11 Afasias natildeo fluentes
bull 71 Depressatildeo
bull 49 Queixa subjetiva de memoacuteria
bull DA -100
bull DA prodromica-100
bull 439 dos outros pacientes tbpositivos
bull 818 ACP
bull 788 Afasia logopecircnica
bull 50 DCL
bull 458 DCB
bull 454 afasias natildeo fluentes
bull 366 demecircncia semacircnticas
bull 145 das DFT
bull 117 (Depressatildeo e QSM)
E o teste de Memoacuteria
bull Sensibilidade100
bull Especificidade de 748
bull Intrusotildees Sensibilidade de 83 e Especificidade72
bull 273 tinham deacuteficit hipocampal
bull 366 dos deprimidos
bull 40 DCL
bull 375 PSP
bull 319 DFT
bull 273 Afasia natildeo fluente
bull 227 ACP
bull 22 Demecircncia Semacircntica
bull 22 DCB
bull 58 Afasia logopecircnica
Existiu uma correlaccedilatildeo desempenho com os marcadores
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
PET Tau and Amyloid-β Burden in Mild Alzheimers Disease Divergent Relationshipwith Age Cognition and Cerebrospinal Fluid BiomarkersKoychev I1 Gunn RN23 Firouzian A2 Lawson J1 Zamboni G1 Ridha B4 Sahakian BJ5 Rowe JB6 Thomas A7 Rochester L7 Ffytche D8 Howard R9 Zetterberg H9101112 MacKay C1 Lovestone S1 Deep and Frequent Phenotyping study team
J Alzheimers Dis 2017 Aug 8
PET Marcador Amiloacuteide
Vantagens
bull Refletem o processo patoloacutegico
bull Conseguem detectar indiviacuteduos assintomaacuteticos em risco
bull Predizem piora cliacutenica
Limitaccedilotildees
bull Custo
bull Disponibilidade
bull Normalizaccedilatildeo de pontos de corte
Caso
bull PET-Amiloacuteide
241 Estudos
11341 Pacientes
7086 Pacientes
Entatildeo vamos coletar Liacutequor para todos
Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory ClinicPatients in a Prospective CohortHandels RL12 Joore MA23 Vos SJ1 Aalten P1 Ramakers IH1 Rikkert MO4 Scheltens P5 Jansen WJ1 Visser PJ15 van Berckel BM5 van Domburg P6 Smid M7 Hoff E8 Hoogmoed J910 Bouwman F5 Claassen J4 Leentjens AF1 Wolfs CA1 Severens JL11 Verhey FR1Author information
bull 200 DA
bull 16 DA prodromica
bull 69 DFT
bull 59 DCB
bull 16 PSP
bull 44 DCL
bull 22 ACP
bull 41 Demecircncia Semacircntica
bull 52 Afasias logopecircnicas
bull 11 Afasias natildeo fluentes
bull 71 Depressatildeo
bull 49 Queixa subjetiva de memoacuteria
bull DA -100
bull DA prodromica-100
bull 439 dos outros pacientes tbpositivos
bull 818 ACP
bull 788 Afasia logopecircnica
bull 50 DCL
bull 458 DCB
bull 454 afasias natildeo fluentes
bull 366 demecircncia semacircnticas
bull 145 das DFT
bull 117 (Depressatildeo e QSM)
E o teste de Memoacuteria
bull Sensibilidade100
bull Especificidade de 748
bull Intrusotildees Sensibilidade de 83 e Especificidade72
bull 273 tinham deacuteficit hipocampal
bull 366 dos deprimidos
bull 40 DCL
bull 375 PSP
bull 319 DFT
bull 273 Afasia natildeo fluente
bull 227 ACP
bull 22 Demecircncia Semacircntica
bull 22 DCB
bull 58 Afasia logopecircnica
Existiu uma correlaccedilatildeo desempenho com os marcadores
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
PET Marcador Amiloacuteide
Vantagens
bull Refletem o processo patoloacutegico
bull Conseguem detectar indiviacuteduos assintomaacuteticos em risco
bull Predizem piora cliacutenica
Limitaccedilotildees
bull Custo
bull Disponibilidade
bull Normalizaccedilatildeo de pontos de corte
Caso
bull PET-Amiloacuteide
241 Estudos
11341 Pacientes
7086 Pacientes
Entatildeo vamos coletar Liacutequor para todos
Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory ClinicPatients in a Prospective CohortHandels RL12 Joore MA23 Vos SJ1 Aalten P1 Ramakers IH1 Rikkert MO4 Scheltens P5 Jansen WJ1 Visser PJ15 van Berckel BM5 van Domburg P6 Smid M7 Hoff E8 Hoogmoed J910 Bouwman F5 Claassen J4 Leentjens AF1 Wolfs CA1 Severens JL11 Verhey FR1Author information
bull 200 DA
bull 16 DA prodromica
bull 69 DFT
bull 59 DCB
bull 16 PSP
bull 44 DCL
bull 22 ACP
bull 41 Demecircncia Semacircntica
bull 52 Afasias logopecircnicas
bull 11 Afasias natildeo fluentes
bull 71 Depressatildeo
bull 49 Queixa subjetiva de memoacuteria
bull DA -100
bull DA prodromica-100
bull 439 dos outros pacientes tbpositivos
bull 818 ACP
bull 788 Afasia logopecircnica
bull 50 DCL
bull 458 DCB
bull 454 afasias natildeo fluentes
bull 366 demecircncia semacircnticas
bull 145 das DFT
bull 117 (Depressatildeo e QSM)
E o teste de Memoacuteria
bull Sensibilidade100
bull Especificidade de 748
bull Intrusotildees Sensibilidade de 83 e Especificidade72
bull 273 tinham deacuteficit hipocampal
bull 366 dos deprimidos
bull 40 DCL
bull 375 PSP
bull 319 DFT
bull 273 Afasia natildeo fluente
bull 227 ACP
bull 22 Demecircncia Semacircntica
bull 22 DCB
bull 58 Afasia logopecircnica
Existiu uma correlaccedilatildeo desempenho com os marcadores
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
Caso
bull PET-Amiloacuteide
241 Estudos
11341 Pacientes
7086 Pacientes
Entatildeo vamos coletar Liacutequor para todos
Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory ClinicPatients in a Prospective CohortHandels RL12 Joore MA23 Vos SJ1 Aalten P1 Ramakers IH1 Rikkert MO4 Scheltens P5 Jansen WJ1 Visser PJ15 van Berckel BM5 van Domburg P6 Smid M7 Hoff E8 Hoogmoed J910 Bouwman F5 Claassen J4 Leentjens AF1 Wolfs CA1 Severens JL11 Verhey FR1Author information
bull 200 DA
bull 16 DA prodromica
bull 69 DFT
bull 59 DCB
bull 16 PSP
bull 44 DCL
bull 22 ACP
bull 41 Demecircncia Semacircntica
bull 52 Afasias logopecircnicas
bull 11 Afasias natildeo fluentes
bull 71 Depressatildeo
bull 49 Queixa subjetiva de memoacuteria
bull DA -100
bull DA prodromica-100
bull 439 dos outros pacientes tbpositivos
bull 818 ACP
bull 788 Afasia logopecircnica
bull 50 DCL
bull 458 DCB
bull 454 afasias natildeo fluentes
bull 366 demecircncia semacircnticas
bull 145 das DFT
bull 117 (Depressatildeo e QSM)
E o teste de Memoacuteria
bull Sensibilidade100
bull Especificidade de 748
bull Intrusotildees Sensibilidade de 83 e Especificidade72
bull 273 tinham deacuteficit hipocampal
bull 366 dos deprimidos
bull 40 DCL
bull 375 PSP
bull 319 DFT
bull 273 Afasia natildeo fluente
bull 227 ACP
bull 22 Demecircncia Semacircntica
bull 22 DCB
bull 58 Afasia logopecircnica
Existiu uma correlaccedilatildeo desempenho com os marcadores
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
241 Estudos
11341 Pacientes
7086 Pacientes
Entatildeo vamos coletar Liacutequor para todos
Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory ClinicPatients in a Prospective CohortHandels RL12 Joore MA23 Vos SJ1 Aalten P1 Ramakers IH1 Rikkert MO4 Scheltens P5 Jansen WJ1 Visser PJ15 van Berckel BM5 van Domburg P6 Smid M7 Hoff E8 Hoogmoed J910 Bouwman F5 Claassen J4 Leentjens AF1 Wolfs CA1 Severens JL11 Verhey FR1Author information
bull 200 DA
bull 16 DA prodromica
bull 69 DFT
bull 59 DCB
bull 16 PSP
bull 44 DCL
bull 22 ACP
bull 41 Demecircncia Semacircntica
bull 52 Afasias logopecircnicas
bull 11 Afasias natildeo fluentes
bull 71 Depressatildeo
bull 49 Queixa subjetiva de memoacuteria
bull DA -100
bull DA prodromica-100
bull 439 dos outros pacientes tbpositivos
bull 818 ACP
bull 788 Afasia logopecircnica
bull 50 DCL
bull 458 DCB
bull 454 afasias natildeo fluentes
bull 366 demecircncia semacircnticas
bull 145 das DFT
bull 117 (Depressatildeo e QSM)
E o teste de Memoacuteria
bull Sensibilidade100
bull Especificidade de 748
bull Intrusotildees Sensibilidade de 83 e Especificidade72
bull 273 tinham deacuteficit hipocampal
bull 366 dos deprimidos
bull 40 DCL
bull 375 PSP
bull 319 DFT
bull 273 Afasia natildeo fluente
bull 227 ACP
bull 22 Demecircncia Semacircntica
bull 22 DCB
bull 58 Afasia logopecircnica
Existiu uma correlaccedilatildeo desempenho com os marcadores
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
Entatildeo vamos coletar Liacutequor para todos
Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory ClinicPatients in a Prospective CohortHandels RL12 Joore MA23 Vos SJ1 Aalten P1 Ramakers IH1 Rikkert MO4 Scheltens P5 Jansen WJ1 Visser PJ15 van Berckel BM5 van Domburg P6 Smid M7 Hoff E8 Hoogmoed J910 Bouwman F5 Claassen J4 Leentjens AF1 Wolfs CA1 Severens JL11 Verhey FR1Author information
bull 200 DA
bull 16 DA prodromica
bull 69 DFT
bull 59 DCB
bull 16 PSP
bull 44 DCL
bull 22 ACP
bull 41 Demecircncia Semacircntica
bull 52 Afasias logopecircnicas
bull 11 Afasias natildeo fluentes
bull 71 Depressatildeo
bull 49 Queixa subjetiva de memoacuteria
bull DA -100
bull DA prodromica-100
bull 439 dos outros pacientes tbpositivos
bull 818 ACP
bull 788 Afasia logopecircnica
bull 50 DCL
bull 458 DCB
bull 454 afasias natildeo fluentes
bull 366 demecircncia semacircnticas
bull 145 das DFT
bull 117 (Depressatildeo e QSM)
E o teste de Memoacuteria
bull Sensibilidade100
bull Especificidade de 748
bull Intrusotildees Sensibilidade de 83 e Especificidade72
bull 273 tinham deacuteficit hipocampal
bull 366 dos deprimidos
bull 40 DCL
bull 375 PSP
bull 319 DFT
bull 273 Afasia natildeo fluente
bull 227 ACP
bull 22 Demecircncia Semacircntica
bull 22 DCB
bull 58 Afasia logopecircnica
Existiu uma correlaccedilatildeo desempenho com os marcadores
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
bull 200 DA
bull 16 DA prodromica
bull 69 DFT
bull 59 DCB
bull 16 PSP
bull 44 DCL
bull 22 ACP
bull 41 Demecircncia Semacircntica
bull 52 Afasias logopecircnicas
bull 11 Afasias natildeo fluentes
bull 71 Depressatildeo
bull 49 Queixa subjetiva de memoacuteria
bull DA -100
bull DA prodromica-100
bull 439 dos outros pacientes tbpositivos
bull 818 ACP
bull 788 Afasia logopecircnica
bull 50 DCL
bull 458 DCB
bull 454 afasias natildeo fluentes
bull 366 demecircncia semacircnticas
bull 145 das DFT
bull 117 (Depressatildeo e QSM)
E o teste de Memoacuteria
bull Sensibilidade100
bull Especificidade de 748
bull Intrusotildees Sensibilidade de 83 e Especificidade72
bull 273 tinham deacuteficit hipocampal
bull 366 dos deprimidos
bull 40 DCL
bull 375 PSP
bull 319 DFT
bull 273 Afasia natildeo fluente
bull 227 ACP
bull 22 Demecircncia Semacircntica
bull 22 DCB
bull 58 Afasia logopecircnica
Existiu uma correlaccedilatildeo desempenho com os marcadores
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
E o teste de Memoacuteria
bull Sensibilidade100
bull Especificidade de 748
bull Intrusotildees Sensibilidade de 83 e Especificidade72
bull 273 tinham deacuteficit hipocampal
bull 366 dos deprimidos
bull 40 DCL
bull 375 PSP
bull 319 DFT
bull 273 Afasia natildeo fluente
bull 227 ACP
bull 22 Demecircncia Semacircntica
bull 22 DCB
bull 58 Afasia logopecircnica
Existiu uma correlaccedilatildeo desempenho com os marcadores
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
Liacutequor
Vantagens
bull Possibilidade de dosagem de vaacuterios marcadores
bull Predizem quem podem evoluir
bull Podem ajudar no diferencial
bull Avalia carga amiloide e dano neuronal
Limitaccedilotildees
bull Invasivo
bull Erros preacute-analiacuteticos
bull Natildeo padronizaccedilatildeo
bull Custo (+-)
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
Caso
bull Liacutequor AB 453 TAU250 Fosfo TAU82
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
Biomarcador Ideal
bull Alta Sensibilidade e Especificidade
bull Faacutecil Realizaccedilatildeo
bull Baixo Custo
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
E agora
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
Sangue
bull Perfil lipiacutedico no sangue
bull TAU
bull AB (inicial mais promissor)
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
E A NOSSA PACIENTE
bull DA X DCB
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
Mov Disords 2015
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
Caso
bull Mutaccedilatildeo no Gen da Presenilina 1
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
ABN Recomendaccedilotildees examescomplementares
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
ABN Recomendaccedilotildees examescomplementares
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
Conclusotildees
bull Noacutes pacientes com CCL eles conseguem predizer que corre maiorrisco (intervenccedilotildees futuras)
bull Confirmaccedilatildeo de formas atiacutepicas
bull PETSPECT e RM padrotildees de atrofia que satildeo bastantes sugestivos
bull Sua normalidade estaacute relacionada a melhor prognoacutestico
bull Disponibilidade custos operacionais e pouco influecircncia no curso da doenccedila limitam sua aplicaccedilatildeo de rotina
Obrigado pela atenccedilatildeonaffrotayahoocombr
Obrigado pela atenccedilatildeonaffrotayahoocombr