IPA08 - Progression of MCI To Dementia [April 2008]
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Transcript of IPA08 - Progression of MCI To Dementia [April 2008]
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Relative Risk of Progression of MCI to Dementia
Pooled and Meta-Analysis of 39 Robust Inception Cohort Studies
Alex MitchellConsultant & Hon SnR Lecturer in Liaison Psychiatry, Leicester
Moj FeshkiStR in Psychiatry
Srini MalladiConsultant in Old Age Psychiatry, Northampton
IPA, Dublin 2008
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What is MCI?
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The Natural History of Dementia
PRE-SYMPTOMATIC
PRE-CLINICAL
CLINICAL
Pathological Burden
Dis
ease
Sev
erit
y
Time in Years
T0
T-5 T+10
T-10 T+5
(Bra
in V
olu
me
/ In
trac
ran
ial V
olu
me)
80%
85%
90%
75%
70%
Severe Dementia
Moderate Dementia
Mild Dementia
Mild Cognitive Impairment
23v24
30
20v21
9v10
Dia
gnos
is
Dea
th
11v12
MM
SE
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Stages of Dementia
VI(Cortical association
areas)
All38+6-730-11Severe Alzheimer’s disease
V(Basal cortex)
Semantic MemoryVisuospatial awarenessOrientation
21-375212-20Moderate Alzheimer’s disease
III/IV(Amygdala & Thalamus)
Recognition MemorySpatial Episodic MemoryExecutive Dysfunction
13-204121-23Early Alzheimer’s disease
II(CA1 field of
hippocampus)
Verbal Episodic Memory(Delayed Recall)
1-1330.521-29Mild Cognitive Impairment
II(CA1 field of
hippocampus)
Verbal Episodic Memory (Extended Recall)
1-1220.524-29Age-Associated Memory Impairment
I(Transentorhinal
area)
No Problems01030Healthy Elderly
Braak StagingCognitive PerformanceADAS-Cog
GDSCDRMMSEStage
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1. Subjective Memory complaintSpontaneous or affirmed?
2. Normal activities of daily livingNormal or near normal?
3. Memory impaired for age1.5SD?
4. No dementiaQuestionable dementia?
Simple Definition Peterson (Mayo Defn) 1997/1999/2001
Winblad B, Palmer K, Kivipelto M, et al. Mild cognitive impairment—beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med 2004;256:240–6.
Portet F, Ousset PJ, Visser PJ, Frisoni GB, Nobili F, Scheltens P, Vellas B, Touchon J . Mild cognitive impairment (MCI) in medical practice: a critical review of the concept and new diagnostic procedure. Report of the MCI Working Group of the European Consortium on Alzheimer's Disease. Journal Of Neurology Neurosurgery And Psychiatry 2006;77 (6): 714-718 .
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Author (year) N Age Study Prev (%)
Graham (1997) 1800 >65 CSHA 5.3
Larrieu (2002) 1265 70-90 PAQUID 2.8
Hanninen (2002) 806 60-76 KUPIO 5.3
Lopez (2003) 2470 >75 CHS 6.0
Fisk (2003) 1790 >65 CSHA 1-3
Ganguli (2004) 1248 >65 MoVIES 3-4
Prevalence of MCI
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What is the Risk of Dementia in MCI?
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Progression, Peterson, 1999
Petersen RC et al: Arch Neurol 56:303, 1999
MCI → AD 12%/yr
50
60
70
80
90
100
Initial 12 24 36 48exam Months
Control → AD 1-2%/yr
50
60
70
80
90
100
Initial 12 24 36 48exam Months
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100
88
76
64
52
40
28
16
40
0
10
20
30
40
50
60
70
80
90
100
Baseline Year 1 Year 2 Year 3 Year 4 Year 5 Year 6 Year 7 Year 8 Year 9
ExtrapolationCrude Mayo MCI Model
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Rivastigmine InDDEX Study
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Rivastigmine InDDEX Study
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Cochrane Review
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AChE for MCI?
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Pooled Effect of Ache for MCIRR Meta-analysis (fixed effects)
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ACR for MCI to Dementia by Intervention
6.3%
8.0%
9.9%
0
1
2
3
4
5
6
7
8
9
10
Drug Placebo VitE
n=4 n=4 n=1
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Pooled Analysis
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Pooled Analysis - Methods
• Systematic search + appraisal + extraction
• Focus on robust studies– Follow-up 3yrs+– Sample n > 50
• Expecting ?20 papers– 65 studies– 15 long term– Sample = 11,756
4x
2x
10x
9x
17x
AD
13926xAACD
23085xCIND
9022xCDR
464412xPartial
251110xClassical
N=DementiaType
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0
2
4
6
8
10
12
4 5 6 7 8 9 10
Years of Observation
Annual Rate of Conversion (%)
Hansson et al (2007)
Bozoki et al (2001)
Visser & Verhey (2008)
Devanand et al (2007) Annerbo et al (2006)Visser et al (2006)
Ganguli et al (2004)
Tyas et al (2004)
Hogan & Ebly (2000)
Ishikawa & Ikeda (2007)
Grober et al (2000)
Larrieu et al (2002)
Dickerson et al (2007) Aggarwal et al (2005)
Busse et al (2006)
Triangle = Specialist Centres (clinical)Square = Community Studies (non-clinical)
Long Term Studies 5yrs+
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y = -5.9607Ln(x) + 16.633R2 = 0.1857
0
2
4
6
8
10
12
14
16
18
20
2 3 4 5 6 7 8 9 10
Years of Observation
ACRMedium+Long Term Studies 3yrs+
Triangle = DementiaSquare = Alzheimer’s disease
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ACR to AD
0.08
0.04
0.07
0.09
0.04
0.09
0.05
0.06
0.09
0.04
0.00
0.01
0.02
0.03
0.04
0.05
0.06
0.07
0.08
0.09
0.10
Classical MCI Partial MCI CDR=0.5 CIND AACD
All
Specialist Settings
Long Term Studies 3yrs+
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Weakness in Model?
• 1-2% Die per year
• 2-5% Recover per year
• ? Lost to follow-up
• => Inception vs Completer studies
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0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
CP1183493-10
Years after enrollment
Alive (%)
NormalsNormalsAll amnestic MCIAll amnestic MCI
P<0.0001
Mayo Data Survival (Kaplan-Mayer)
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0
1
2
3
45
67
89
10
17
0
2
4
6
8
10
12
14
16
1922
20
100
85
7465
5750
4337
3124
18
8
0
10
20
30
40
50
60
70
80
90
100
Baseline Year 1 Year 2 Year 3 Year 4 Year 5 Year 6 Year 7 Year 8 Year 9 Year 10 Year 15
MCI-StableRecoveredDiedDementia
ExtrapolationAdvanced All Case MCI Model
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Extras
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Non-Amnestic MCISingle Domain
Yes
Amnestic MCISingle Domain
Yes
Cognitive complaint
Not normal for age
Modest Objective Cognitive decline
Normal instrumental function
Yes
Amnestic MCI
MCI
Memory impaired? No
Non-Amnestic MCI
Single non-memorycognitive domain
impaired?
Memoryimpairment only? No
Non-Amnestic MCIMultiple Domain
No
Amnestic MCIMultiple Domain
Petersen: J Int Med, 2004
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Credits / Acknowledgments
For more slides www.psycho-oncology.info/slides
Alex J Mitchell © 2008