Identification of Early Cognitive Impairment - Centenary After Hours ...

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Dec 14, 2013 (3 years and 8 months ago)

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Identifying Early Cognitive Impairment

11
th

Annual GTA Primary Care Symposium








Sharon Cohen MD FRCPC

November 9, 2013






Toronto Memory Program

Objectives


Following this talk, participants will:



Be able to differentiate between normal aging, mild
cognitive impairment and dementia


Understand the rationale for detecting early
cognitive impairment


Recognize appropriate situations for screening


Identify appropriate cognitive screening tools


Appreciate recommendations and options for
management of early cognitive impairment


S.Cohen


Toronto
Memory Program

Disclosures




Research Grants, Advisory Board Member,
Speaker Honoraria from:


AbbVie
; Baxter; Genentech; Lilly;

Lundbeck
; Merck; Novartis; Pfizer;



Roche;
Servier
;
TauRx






S.Cohen

Toronto Memory Program

Background


Individuals are increasingly concerned about
their cognitive health


Life expectancy keeps rising (2009: M:79; F:84)


Aging is associated with predictable cognitive
changes that are not pathological


Aging is also the main risk factor for AD


S.Cohen Toronto Memory Program

S.Cohen


Toronto
Memory Program

Am I developing Alzheimer’s Disease?

S.Cohen Toronto Memory Program

Am I developing Alzheimer’s Disease?

S.Cohen Toronto Memory Program

Pathological Signature of AD

amyloid

tau

Early Detection Allows For:




Treatment
of
reversible and/or exacerbating factors
(e.g., depression, sleep apnea, drug side effects, thyroid deficiency)


Optimization of
patient
care through education,
support services, medications


Planning for future care


Participation in clinical trials


Care and support for caregivers


S.Cohen


Toronto
Memory Program

Who to Screen for Cognitive Impairment?

Current guidelines for screening:


No

for population screening



Yes

for case finding


Cognition should be assessed whenever there is
a concern re: cognitive decline from any of:


The Patient



An Informant


The Clinician

S.Cohen


Toronto
Memory Program

Barriers to Early Detection


≥ 50% dementia
cases
go unrecognized
in primary
care


Canadian FPs identify the main barriers to identification
and management of dementia as:


Limited
training on dementia


Diagnostic uncertainty


Lack of access to
resources
(e.g.,
specialists)


Lack of time



Pimlott

NJ
et al. Can Fam
Physician

2009; 55(5
):508
-
9
. World
Health Organization.
Dementia: A Public Health Priority.
2012.
Available at: http
://www.who.int/mental_health/
publications
/dementia_report_2012
. Accessed: February 27, 2013.

S.Cohen


Toronto
Memory Program

Dementia


Decline in two or more cognitive domains


Significant impact on daily function


o
Alzheimer’s disease the most common cause in
those over age 65






S.Cohen


Toronto
Memory Program

Mild Cognitive Impairment


Decline in one or more cognitive domains


Daily function relatively intact


o
Many possible underlying causes

o
High risk for progression to dementia







S.Cohen


Toronto
Memory Program

Age Associated Cognitive Decline (AACD)


Starts as early as the 4
th

decade


Decline in multiple cognitive domains
-

but
within 1.5 SD of norm


Characterized by a reduction in:

o
Speed of recall; Reaction time; Incidental learning;

o

Source memory; Ability to shift set/multitask



S.Cohen


Toronto
Memory Program

AACD: The Good News


Many aspects of cognition remain stable or improve:

o
Semantic memory remains strong

o
Procedural memory remains strong

o
Insight, judgment, decision making remain
strong or increase

o
Vocabulary continues to increase









S.Cohen Toronto Memory Program

S.Cohen


Toronto
Memory Program











S.Cohen Toronto Memory Program

John North

PhD Philosophy

Age 93


AACD versus MCI


AACD



Concern voiced regarding
cognitive decline



No objective deficits on
testing
(scores within 1.5 SD)



Preserved daily function


MCI


Concern voiced regarding
cognitive decline




Objective cognitive deficits
in one or more domains



Relatively preserved daily
function


S.Cohen


Toronto
Memory Program


MCI versus Dementia


MCI


Concern re: change in
cognition voiced by patient
or informant



Objective cognitive deficits
>1.5 SD for age and education
in one or more domains



Daily function relatively
preserved


Dementia


Concern re: change in
cognition voiced by patient
or informant



Objective cognitive deficits
>1.5 SD for age and education
in two or more domains



Daily function significantly
impaired


S.Cohen


Toronto
Memory Program

Cognitive Assessment Options

1.
Bedside paper and pencil test:
e.g., MMSE, CDT,
MoCA
, Quick Screen, MIS,
Mini
-
Cog


2.
Detailed neuropsychological test batteries:
e.g.,
Weschler
,
Stroop
, Wisconsin Card Sort


3.
Computerized screening tests:
e.g.,
Cognigram
;
CogSport
;
Cognistat


S.Cohen


Toronto
Memory Program

Paper and Pencil Screening Tools


Majority designed to screen for dementia and
are insensitive for mild deficits


MMSE sensitive to moderate severity
dementia but unable to distinguishing AACD
from MCI from early dementia


Of bedside paper and pencil tests, only
MoCA

is sensitive for MCI (90% sensitivity versus
17% for MMSE in MCI)

S.Cohen


Toronto
Memory Program

Neuropsychological Testing


May assists in diagnosis of atypical cases, e.g.,
those with non
-
amnestic

deficits


Lengthy test sessions; limited availability;
expensive for patient


Not required for routine diagnostic work
-
up of
dementia (CCCDTD)




Chertkow
H
et al. Can J Neurol Sci
2001
; 28(Suppl
1):
28
-
41;

Chui H, Zhang Q.
Neurology

1997
; 49(4):925
-
35;

Jacova C
et al. Alzheimers Dement

2007; 3(4):299
-
317.


S.Cohen


Toronto
Memory Program

Computerized Cognitive Screening Tools


Used extensively in clinical trials for safety
monitoring


Can provide more objective and reliable testing


Can incorporate flexibility in test paradigm


Can free up MD time, staff, resources


S.Cohen


Toronto
Memory Program

Cognigram

(
CogState
)


Non
-
verbal, computerized test using playing cards


Detects subtle cognitive change at short intervals


Designed to be culturally and educationally neutral
with minimal language requirement


Sensitivity = 81% for MCI; 100% for AD


Specificity = 82% for MCI; 92% for AD


Good correlation with neuropsychological tests

S.Cohen


Toronto
Memory Program

Darby
DG
et al. J
Alzheimers Dis
2011
; 27(3
):
627
-
37;
Dingwall

K, Carney S.
Australas Psychiatry

2009;

17
(
Suppl 1
)
:S47
-
50
;

Lim
YY
et al. J Clin
Exp Neuropsychol

2012
; 34(4
):
345
-
58;
Maruff

P
et al.

Presented at: AAIC 2013.

Cognigram: Demonstration

Differences in
Cognigram

Performance in
MCI, Alzheimer’s disease, and Healthy Controls

-3.5
-3
-2.5
-2
-1.5
-1
-0.5
0
Detection
Identification
One-card
learning
One back
MCI
Alzheimer's disease
Difference from healthy controls (z
-
scores)

Lim
YY
et al. J Clin Exp Neuropsychol

2012; 34(4):345
-
58.

Determining Functional Impairment


The weakest link in assessing mild patients


No problem determining once BADL impaired


However, mild patients may still be
independent

in
IADL but:


Not at their previous level


No longer performing IADL which are or would be
problematic


Therefore must consider previous level as baseline







Detects subtle cognitive change at short intervals


Designed to be culturally and educationally neutral
with minimal language requirements


Sensitivity = 81% for MCI; 100% for AD


Specificity = 82% for MCI; 92% for AD


Good correlation with neuropsychological tests

S.Cohen


Toronto
Memory Program


A Few Words About Biomarkers


Revised Diagnostic Criteria for AD (NIA
-
AA 2011)
recognizes 3 stages of AD:


Preclinical AD


MCI due to AD


AD Dementia


Proposes use of biomarkers (3 imaging; 2 CSF) to
enhance diagnostic certainty (particularly in the
pre
-
clinical and MCI stage of disease)

S.Cohen Toronto Memory Program

S.Cohen


Toronto
Memory Program

PET Amyloid Imaging

The Window of Opportunity


Primary Prevention:

o
The long pre
-
symptomatic stage of AD suggests that
interventions to prevent disease should start in young
to mid life


Secondary Prevention:

o
Early detection of AD at a pre
-
symptomatic or mild
stage allows for interventions prior to the
development of significant brain damage and
functional impairment


S.Cohen Toronto Memory Program

S.Cohen


Toronto
Memory Program

April 2012:

FDA Approves Amyvid for Clinical Use


Amyvid
™ (
Florbetapir

F 18 Injection)


The first agent approved for
clinical use
to


detect
amyloid

plaque in patients under


evaluation for AD


Not yet available in Canada…


S.Cohen Toronto Memory Program

Management of MCI


Requires monitoring over time due to high risk of
progression (AAN; CCCD3)


Requires investigations for underlying etiology
including identification and management of
vascular factors (NIA
-
AA; CCCDTD)


Includes promotion of a brain healthy lifestyle:
physical & mental activity; social engagement;
dietary pattern; sleep hygiene; stress management


Consider referral for secondary prevention trials

S.Cohen


Toronto
Memory Program

Recommendations for MCI/Dementia in
those under 65
(“early onset dementia”)


All patients with early onset dementia should
be referred to a memory clinic, preferably
with
access to genetic counselling
& genetic testing


Physicians
should be sensitive to
special
issues
associated with early onset dementia
, e.g.,
employment, family responsibilities, access
to
age appropriate support services


Gauthier S
et al
; CCDTD4 participants.
Can Geriatr J

2012; 15(4):120
-
6.

S.Cohen


Toronto
Memory Program

Driving and MCI/Dementia:

CCCD3 Recommendations


Counsel patients
that driving cessation is an inevitable
consequence of progressive dementias and planning
for this should occur early


Cognitive tests are insufficient to judge driving ability


Gold standard: specialized on
-
road
driving
evaluation;
patients have a legal right to this test


Patient with who are deemed safe to drive require re
-
evaluation q 6

12 months or
sooner if
indicated

Hogan DB
et al. CMAJ

2008; 179(8
):787
-
93.

S.Cohen


Toronto
Memory Program

Summary


Cognitive concerns require cognitive screening


MoCA

&
Cognigram

are sensitive tools for MCI and
early dementia


Determining functional impairment (to distinguish
dementia from MCI) requires thoughtful history taking


MCI management includes monitoring, attention to risk
factors, and consideration of prevention trials


Those < 65 have additional needs & should be referred


Biomarkers enhance diagnostic certainty and will be of
increasing importance over the next several years

S.Cohen


Toronto
Memory Program

Am I developing Alzheimer’s Disease?

S.Cohen

Toronto
Memory Program