Embed Size (px)
Citation preview
6/6/2019
1
v.s.
Asst. Prof. Chatchawan Rattanabannakit, MD.Division of Neurology, Department of Medicine
Faculty of Medicine Siriraj Hospital, Mahidol University
Dementia Association of Thailand Annual Conference
June 6th -7th, 2019
Definition and
Diagnosis: MCI vs SCD
2
CLINICAL SPECTRUM IN ALZHEIMER’S DISEASE
Preclinical MCI Dementia
Adapted from: Jack Jr CR, et al. Brain. 2010;133:3336–48.
AβTau
Brain
structure Cognition
Clinical
functionDecades
3
EVOLUTION OF THE MCI CRITERIA
Petersen RC. Continuum (Minneap Minn) 2016; 22(2): 404-184
CRITERIA FOR AMNESTIC MCI
5 6
6/6/2019
2
DSM-5: MILD NEUROCOGNITIVE DISORDER
A. Evidence of modest cognitive decline from a previous level of performance in
one or more cognitive domains (complex attention, executive function, learning and memory, language,
perceptual- motor, or social cognition) based on:
1. Concern of the individual, a knowledgeable informant, or the clinician that there has been
a mild decline in cognitive function; and
2. A modest impairment in cognitive performance, preferably documented by standardized
neuropsychological testing or, in its absence, another quantified clinical assessment.
B. The cognitive deficits do not interfere with capacity for independence in
everyday activities (i.e., complex instrumental activities of daily living such as paying bills or managing medications
are preserved, but greater effort, compensatory strategies, or accommodation may be required).
C. The cognitive deficits do not occur exclusively in the context of a delirium.
D. The cognitive deficits are not better explained by
another mental disorder (e.g., major depressive disorder, schizophrenia).
7 8
Petersen RC. Continuum (Minneap Minn) 2016; 22(2): 404-18
ALZHEIMER’S DISEASE SPETRUM
Subjective
Cognitive
Complaint
Modified from
9
TERMS USED FOR SUBJECTIVE COMPLAINTS
Subjective cognitive decline (SCD)
Subjective memory impairment (SMI)
Subjective cognitive complaint (SCC)
Subjective memory concern (SMC)
Cognitive complainer (CC)
10
SCD PRECEDING THE MCI AND AD
Normal adult MCI AD
Subjective cognitive impairment
11Jessen F, et al. Alzheimers Dement. 2014
12
6/6/2019
3
Adapted from: Jessen F, et al. Alzheimers Dement. 2014
Preclinical AD MCI/prodromal AD Dementia
Onset of decline
in cognitive performance
Impairment on a
cognitive test
Age-, sex- and education adjusted
normal performance range
Co
gn
itiv
e p
erf
orm
an
ce
Progression of disease pathology and clinical states
Subjective cognitive decline (SCD)(Indicating compensation and subtle decline in cognitive performance)
Concept of Subjective Cognitive Decline (SCD) in
preclinical AD
13
Research criteria for pre-MCI subjective cognitive
decline (SCD)
1 and 2 must be present
1. Self-experienced persistent decline in cognitive capacity in comparison with a previously normal status and unrelated to an acute event.
2. Normal age-, gender-, and education-adjusted performance on standardized cognitive tests, which are used to classify mild cognitive impairment (MCI) or prodromal AD.
Exclusion criteria
Mild cognitive impairment, prodromal AD, or dementia
Can be explained by a psychiatric* or neurologic disease (apart from AD), medical disorder, medication, or substance use
Jessen F, et al. Alzheimers Dement. 2014
*Individual symptoms of depression or anxiety, which do not reach
the threshold of a disorder, are not considered exclusion criteria
14
COGNITIVE COMPLAINT ASSESSMENT
Clinical interview: Subjectively
YES/NO Question
Graded response question
Validated tests such as MAC-Q, Ecog, AD8, CCI etc.
Whom should be evaluated?
Patient**
Knowledgeable informant
Both 15
Self-report VS Informants-report
The report of an individual’s cognitive decline by informants was
better correlated with objective cognitive test performance than the
report by the subject themselves and may be a better predictor of
subsequent MCI or dementia1-5.
Moreover, as compared to informant-only or self-only report of
cognitive decline, using the mutual report by both subjects and
informants was found to be a better prediction of diagnostic
outcome and associated with the worst cognitive trajectory6-7.
1. Gavett R, et al. Alz Dis Assoc Dis. 2011
2. Rami L, et al. J Alzheimers Dis. 2014
3. Slavin MJ, et al. Am J Geriat Psychiat. 2014
4. Rabin LA, et al. J Am Geriatr Soc. 2012
5. Caselli RJ, et al. Alzheimers Dement. 2014
6. Gifford KA, et al. Alzheimers Dement. 2013
7. Gifford KA, et al. J Alzheimer Dis. 2015 16
17
Other consideration in diagnosis of SCD
It is acknowledged that depression, anxiety and personality may
affect the perception of cognitive decline as well as the objective
cognitive performance1.
In populations with chronic health difficulties, cognitive
complaints may be more highly associated with physical health
symptoms than with objective impairment2.
Linguistic and cultural factors may also influence the report of
cognitive complaints3-4.
181. Jessen F, et al. Alzheimers Dement. 2014
2. Boone KB, et al. Clin Neuropsychol. 2009
3. Jackson JD, et al. Alzheimers Dement. 2016
4. Rabin LA, et al. Annu Rev Clin Psychol. 2017
6/6/2019
4
Diagnosis of Cognitive Impairment
Subjective
Cognitive
Complaints
Objective
Cognitive
Impairment
Functional
Impairment
Biomarkers / Genetics
Subjective Cognitive Decline (SCD)
Functional Impairment(Activities of daily livings: ADL)
Subjective
Cognitive
Complaints
Objective
Cognitive
Impairment
Functional
Impairment
Biomarkers / Genetics
Functional Impairment(Activities of daily livings: ADL)
Mild Cognitive Impairment (MCI)
PREVALENCE
AND THE RISK OF
FUTURE DEMENTIA20
PREVALENCE OF MCI
Overall prevalence of MCI is in the 12 - 18% range in
persons over the age of 60 years.
The Mayo Clinic Study of Aging followed cognitively normal
subjects 70 years and older for a median of 5 years and
found the progression rate to be MCI is in the 5 - 6% per
year range.
Petersen RC. Continuum (Minneap Minn) 2016; 22(2): 404-18 22
DIAGNOSIS OF MCI
Petersen RC. Continuum (Minneap Minn) 2016; 22(2): 404-18
PROGRESSION OF MCI
Golomb J, et al. Dialogues Clin Neurosci. 2004; 6: 351-6723
PROGNOSIS OF MCI
Studies conducted in referral clinics have shown that patients with MCI progress to AD at a rate of 10 -15% (5-17) per year
Rates of conversion also vary according to the duration of follow-up; one analysis compared longer duration (>5 years) to shorter duration studies and found lower rates with longer durations of follow-up
The risk of conversion decreases over time
Typically, patients convert within a period of two to three years;however, longer intervals of up to eight years have been reported
McDade EM, et al. ©2016 UpToDate® Last updated: May 04, 2016.
Lopez OL. Continuum (Minneap Minn) 2013; 19(2): 411-24 24
6/6/2019
5
MCI reversion & MCI stability
The annual reversion rate from MCI to normal cognition was
substantially higher (20%) than the annual progression rate from MCI
to dementia.
While MCI patients may progress to dementia or revert to normal
cognition, a large proportion of MCI patients may remain clinically
stable for their entire observed clinical course.
However, it is unknown for how long MCI patients truly remain stable
since available studies using the Mayo-revised or IWG-expanded MCI
criteria have follow-up periods up to five years.
Pandya SY, et al. J Neurol Sci. 2016; 369: 57-62 25
Predictors of progression of MCI
Age
Neuropsychological testing
Predictors related to AD pathology
ApoE epsilon 4
CSF biomarkers
Neuroimagings
Structural MRI
FDG-PET, Amyloid PET, Tau PET
Psychological features
Cerebrovascular disease and vascular risk factor
Slow gait: Motoric cognitive syndrome
Olfactory dysfunction
±±
26
SUBJECTIVE COGNITIVE DECLINE
Self-perceived cognitive decline is a common
condition in cognitively normal older persons
Prevalence in community-residing persons ≥ 65 years
ranged from 25% - 56%
23% of patients over 65 years presented to GP with
memory complaints
Reisberg B, et al. Alzheimer’s & Dementia. 2010
Archer HA, et al. JAD. 201527
AD BIOMARKER AND SCD
There is evidence that subjectively experience decline is associated with the
increased likelihood of abnormal biomarkers consistent with Alzheimer’s
disease, including findings from cerebrospinal fluid (CSF), structural and
functional magnetic resonance imaging (MRI), and positron emission
tomography (PET) 1-5.
Moreover, SCD with APOE ε4 genotype are associated with high Aβ burden 6.
1. Jessen F, et al. Alzheimers Dement. 2014
2. Visser PJ, et al. Lancet Neurol. 2009
3. Saykin AJ, et al. Neurology. 2006
4. Amariglio RE, et al. Neuropsychologia. 2012
5. Merrill DA, et al.Int Psychogeriatr. 2012
6. Zwan MD, et al. JAD. 201628
Saykin AJ, et al. Neurology. 2006
REDUCTION OF GM DENSITY (MRI)
HC CC MCI HC CC MCI
HC CC MCI HC CC MCI
Left hippocampus volume Right hippocampus volume
Volu
me
Left hippocampal GM Density Right hippocampal GM Density
Gra
y M
att
er
Density
29
SCD with APOE ε4 are associated with high Aβ burden
from AIBL cohortn=307 cognitively normal
n=133 for 18F-flutametamol
scan
Zwan MD, et al. JAD. 201630
6/6/2019
6
Importance of SCD (2)
Longitudinal studies have shown that cognitively normal individuals with
subjective cognitive decline are at a higher risk to progress to MCI or dementia.
1. Luck T, et al. Acta Psychiatr Scand. 2014
2. Jessen F, et al. Alzheimers Dement. 2014
3. Reisberg B, et al. Alzheimers Dement. 2010
4. Krysio RJ, et al. Neurology. 2014
LEILA75+ study
N=443 non-demented
5.4 year follow up
No SCD
SCD
Cum
ula
tive d
em
entia-f
ree s
urv
ival
Luck T, et al. Acta Psychiatr Scand. 201431
Other consideration in SCD
In community, SCD converted to MCI 34.2% over 5.3 years, and
to dementia 10.79% over 5.2 years.
In memory clinic, SCD converted to MCI 16.5-30.0%, and to
dementia 10.0 - 11.7% over 2.5 - 3.5 years.
SCD individuals with worries or consistent SCD are at higher risk.
1. Archer HA, et al. JAD. 2015
2. Eckerstrom M, et al. DADM. 2017
3. Jessen F, et al. Arch Gen Psychiatry. 2010 32
Jessen F, et al. Arch Gen Psychiatry. 2010
No SCD
SCD without worry
SCD with worry
SCD with or without worry
HR 3.04
CI: 1.36-6.81
HR 6.54CI: 2.82-15.20
AgeCoDe n=2423,
cognitively normal
36 months follow-up
33
Inconsistent and Consistent SCD
AgeCoDe Study
n= 1,990 Cognitively
normal
Age > 75
Inconsistent SCD = only one
at baseline or 18th month
Consistent SCD = SCD at
baseline and 18th month
HR 1.45CI: 0.91-2.29
HR 2.09CI: 1.35-3.23
HR 3.99CI: 2.33-6.83
Wolfsgruber S, et al. JAD 2016
Inconsistent SCD
consistent without worries
consistent with worries
34
MANAGEMENT OF
MCI vs SCD
35 36
6/6/2019
7
Management guideline for patients with MCI
Clinicians should wean patients from medications that can contribute
to cognitive impairment and treat modifiable risk factors that may be
contributing (Level B).
Clinicians should counsel the patients and families that there are no
pharmacologic or dietary agents currently shown to have
symptomatic cognitive benefit in MCI and that no medications are
FDA-approved for this purpose (Level B).
Clinicians may choose not to offer cholinesterase inhibitors (Level B).
37Petersen RC, et al. Neurology 2018; 90: 126-135
Management guideline for patients with MCI
For patients diagnosed with MCI, clinicians should recommend regular
exercise (twice/week) as part of an overall approach to management
(Level B).
Clinicians should discuss diagnosis and uncertainties regarding
prognosis (Level B).
In patients with MCI, clinicians may recommend cognitive interventions
(Level C).
38Petersen RC, et al. Neurology 2018; 90: 126-135
Management of patients with SCD
Pharmacologic – heterogeneity, costly, difficult to implement and maintain
Non-pharmacologic
A small effect size was found on cognitive outcomes, greater for cognitive
versus other intervention types. The available evidence suggests that NPI
may benefit current cognitive function in persons with SCD.
Conversely, for individuals presenting with SCD within the context of
mood/anxiety, personality, and health concerns, pharmacologic treatment and
intervention may improve psychological functioning and overall quality of life.
39Rabin LA, et al. Annu Rev Clin Psychol. 2017
Smart CM, et al. Neuropsychol Rev. 2017
IMPORTANCE OF
MCI and SCD
40
Symptomatic
Therapy
Natural History of
Alzheimer’s Disease
Treatment of Alzheimer’s Disease
Cognitive
Function
Years
Disease-Modifying
Therapy (DMT)
Drug development pipeline for AD
112 agents
Up to end of Jan 2018
42
6/6/2019
8
CLINICAL SPECTRUM IN ALZHEIMER’S DISEASE
Preclinical MCI Dementia
Adapted from: Jack Jr CR, et al. Brain. 2010;133:3336–48.
SCD
43
Use of SCD for clinical trials
Buckley RF, et al. J Mol Neurosci. 2016 44
CONTENTS and CONCLUSION
Definition and diagnosis of MCI and SCD
Prevalence and the risk of future dementia
Management of MCI and SCD
Importance of these conditions
45
“Self Complaint & Objective cognitive impairment”
“Dementia risk MCI > SCD > Normal”, “Concern>no concern”
“No drugs”, “non-pharmaco may benefit”
“Early treatment”, “target group treatment”
Thank you!Any question?
Chatchawan Rattanabannakit
46
