The Forgetful Patient – Evaluation and Management

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Dec 14, 2013 (7 years and 10 months ago)

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The Forgetful Patient



Evaluation
and Management

Michael
Sha
, MD, FACP

Governor, Indiana ACP Chapter

Indiana University School of Medicine

2011 Scientific Meeting

Central America ACP Chapter

Panama City, Panama

Dementia

Dementia


Cognitive Spectrum


Normal


Mild Cognitive Impairment (MCI)


Definition
-

most
commonly defined as a subtle but
measurable memory
disorder


American Academy of Neurology (2001)




A
n
individual’s report of
memory
problems, preferably
confirmed by another person


Measurable, greater than normal
memory impairment
detected with standard memory assessment tests


Normal
general thinking and reasoning skills


Ability
to perform normal daily
activities

Dementia

Dementia


Spectrum


Dementia (DSM
-
IV)


I
mpairment of memory


I
mpairment of at least one other cognitive domain


Abstract thinking,


Judgment,


Language, or


V
isuo
-
spatial abilities


D
eterioration should be significant enough to
interfere with work or social relationships


Dementia

Outline


Screening Tools


Treatment Update


Prevention


Management Update

Dementia

Dementia


Evaluation


Early diagnosis, early treatment


Preserve quality of life


Postpone institutionalization


Evaluate for reversible causes


Confounders to diagnosis


Psychiatric disorders (e.g. depression)


Medications


Cognitive decline with normal aging


Low educational attainment

Screening Tests


Mini
-
Mental Status Exam


Clock Drawing


Short Portable Mental Status
Questionnaire


Blessed Dementia Scale


3MS (Modified
-
MMSE)


Fuld

Object
-
Memory Evaluation


Cognitive Abilities Screening
Instrument


Structured Telephone Interview
for Dementia Assessment


MDS Cognitive Performance Scale


Cognitive Impairment Diagnosing
Instrument


Baylor Profound Mental Status
Exam


Severe Impairment Battery (SIB)



Guys Advanced Dementia
Schedule


East Boston Memory Test


7
-
minute Neurocognitive
Screening Battery


Katzman’s

Short Orientation
-
Memory
-
Concentration Test


Time and Change Test


Mattis

Dementia Rating Scale


Hasegawa Dementia Scale
-
Revised


Delayed
-
Word
-
Recall Test


Cognitive Capacity Screening
Examination


Cortical Function Assessment


Mental Status Questionnaire

Dementia

Screening Tests



Mini
-
Mental Status Exam



Clock
Drawing Test



Severe Impairment Battery

Dementia

Mini
-
Mental Status Exam


Published in
1975 in the
Journal of
Psychiatric
Research


An 11
-
item
instrument
designed for
easy and quick
administration

Dementia

Mini
-
Mental Status Exam


30 point scoring scale


5 points for orientation to time


5 points for orientation to place


6 points total for retention and recall


5 points for attention (serial 7’s or “WORLD”)


MMSE score of 23/24 generally accepted as cutoff
for cognitive impairment


83
-
87% sensitivity, 82
-
96% specificity


Sensitivity and specificity affected by age, educational
level

Dementia

Mini
-
Mental Status Exam


Influence of age


MMSE scores decline
with age


MMSE declines 0.6
points per year in
normal patients, 2.8
points in demented
patients
(
Aevarsson

O,
Dementia and Geriatric
Cognitive Disorders, 2000)

(Crum, JAMA, 1993)

Dementia

Mini
-
Mental Status Exam


Influence of education


Education accounts

for
more variance in
MMSE scores than

any
other
factor


MMSE is based on
an 8
th
-
grade level of
education


High education


“Ceiling effect”


(Crum, JAMA, 1993)

Dementia

Mini
-
Mental Status Exam


Additional drawbacks


MMSE
becomes less sensitive as the dementia
progresses



Floor Effect



due to weighting
of the MMSE point
system


Does not adequately assess executive functioning

Dementia

Mini
-
Mental Status Exam


How valid is the Spanish
-
language version of the
MMSE?


Validity study
(
Taussig

IM, Clinical Gerontologist, 1992 and
Taussig

IM,
Journal of the International Neuropsychology Society, 1996)


Conducted through the Spanish
-
Speaking
Alzheimer’s Disease Research Program at the
University of Southern California


168 patients were enrolled (81 dementia, 77
non
-
demented patients)


42% from Mexico, rest were from other Latin
American countries


Dementia

Mini
-
Mental Status Exam


Validity of Spanish
-
language MMSE (S
-
MMSE)


Performance by non
-
demented older Hispanics did not
differ from non
-
demented native English speakers


Implies there is a lack of cultural bias in total scores
from the MMSE and the S
-
MMSE


Education provided similar confounding influence


Dementia

Mini
-
Mental Status Exam


SUMMARY


Rapid to administer and score


MMSE is valid with high sensitivity and specificity and
understanding its limitations with education and age


Longitudinally useful until
patients
progress beyond
moderate
dementia


S
-
MMSE appears equally valid as the MMSE in
diagnosing dementia


Dementia

Clock Drawing Test


Assesses multiple cognitive domains


Relatively quick to administer


Drawbacks


Many types of
errors are
possible


Multiple scoring
systems

Dementia

Clock Drawing
-

Scoring


Most of the scoring systems are complex


limits
utility

Dementia

Clock Drawing
Test


Despite the significant variations in scoring
systems, all of the published scoring systems
have good reliability and inter
-
rater reliability


Most scoring systems have a sensitivity of 85%
and specificity of 85%


Level of education does influence clock drawing scores


Correlation between clock drawing scoring systems


Correlation with MMSE


Can use with
MMSE to increase MMSE sensitivity
and specificity

Dementia

Severe Impairment Battery


40 item, 100 point scale instrument


Focused on evaluating cognitive ability in
severely demented patients


Simple one
-
step commands with gestural cues


Allows for nonverbal and partially correct responses


Composed of 6 major subscales

Attention

Orientation

Language

Memory

Visuo
-
spatial

ability

Construction

Dementia

Severe Impairment Battery


Ability of instrument to differentiate cognitive
performance in dementia patients categorized as
“severe impairment” by MMSE

Dementia

Screening Tests


Need to understand the performance
characteristics of the tests used


Need to balance utility (i.e. ease of use) with need
to document longitudinal progression


Prognosis


Response to treatment

Dementia

Treatment


Acetylcholinesterase

inhibitors


Neuropeptide modifying agent
-

Memantine


Not helpful


Tacrine


Vitamin E


Ginkgo
biloba


Dementia

Acetylcholinesterase

Inhibitors


High
-
dose Donepezil study
(
Farlow

MR, Clinical Therapeutics,
2010)


Randomized double
-
blind study


International, multicenter study (219 centers in Asia,
Europe, Australia, North and South America, and South
Africa)


Study arms


High
-
dose Donepezil (23mg
qd
) for 24 weeks


Standard
-
dose Donepezil (10mg
qd
) for 24 weeks

Dementia

Acetylcholinesterase

Inhibitors


High
-
dose Donepezil study


Inclusion
criteria:


Enrolled patients with probable
Alzheimers

with a
MMSE score of 0 to 20


Taking Donepezil 10mg
qd

for > 12 weeks


Exclusion criteria:


Other neurologic disorders


Outcome measures: Severe Impairment Battery (SIB)
and Clinician’s Interview
-
Based Impression of Change
Plus Caregiver Input Scale (CIBIC+)

Dementia

Acetylcholinesterase

Inhibitors


High
-
dose Donepezil study


Results


1467 patients randomized (981 in the high
-
dose treatment arm, 486 in the standard dose treatment
arm)


Global participation


10 sites from South America


10% of study participants from
South America


Dementia

Acetylcholinesterase

Inhibitors


High
-
dose Donepezil study


SIB


+2.5 in high dose arm
vs

+0.4 in standard dose
(p < 0.001)


CIBIC +


4.23 in high dose arm
vs

4.29 in standard dose
(p = NS)


No benefit in ADL or MMSE
scores

Dementia

Acetylcholinesterase

Inhibitors


High
-
dose Donepezil
study


Side effects


11.8% with nausea in high dose arm
vs

3.4% in
standard dose arm


9.2% with vomiting in high dose arm
vs

2.% in
standard dose arm


8.3% with diarrhea in high dose arm
vs

5.3% in
standard dose arm

Dementia

Acetylcholinesterase

Inhibitors,
Memantine


Where to we stand with drug treatment?


Most drugs with statistically significant benefit but little
clinical improvement
(
Qaseem

A, Annals of Internal Medicine 2008)


High dose Donepezil falls in the same category


May be marginally better standard dose Donepezil


Cost will be a factor


Need to caution patient and family about higher
incidence of side effects


Need to focus on helping families and caregivers adapt
and cope


Dementia

Dementia


Prevention


Exercise


Mentally stimulating activities (“Cognitive Training”)


Acetylcholinesterase

inhibitors and
Memantine



Dementia

Prevention
-

Exercise


Fitness for the Aging Brain Study
(
Lautenschlager

NT, JAMA
2008)


Randomized, single site, 18
-
month study


Study arms


24
-
weeks of home
-
based program of physical activity


Education and usual care


Outcome measure


Alzheimer Disease Assessment
Scale


Cognitive Subscale (ADAS
-
Cog)


Scale consists of 11 brief cognitive tests, scored 0 to
70 (higher number is worse!)

Dementia

Prevention
-

Exercise


Fitness for the Aging Brain Study


Inclusion criteria


Community
-
based older adults recruited


Exclusion criteria


Patients with significant cognitive impairment, likely
depression (based on the Geriatric Depression
Scale), significant alcohol use, history of chronic
mental illness, lack of fluency in English


Intervention


encouragement of 150 minutes of
moderately intense physical activity per week (three 50
-
minute sessions) with periodic reminders

Dementia

Prevention
-

Exercise


Fitness for the Aging Brain Study


Results


170 patients in study (85 in each arm)


Patients in the exercise arm has a statistically
significant improvement in cognition as measured by
the ADAS
-
Cog and in recall of word lists


0.69 point improvement comparing the arms at 18
months

Dementia

Prevention
-

Exercise


Fitness for the Aging Brain Study


Results


170 patients in study (85 in each arm)


Dementia

Prevention
-

Exercise


Adult Change in Thought (ACT) Study
(Larson EB,
Annals of Internal Medicine 2006)


Prospective cohort study to evaluate regular exercise (at
least 3 times per week) on risk for dementia



1740 participants, 65 years of
age and cognitively intact at
baseline


Reassessed every 2 years
(1994
-
2003)

Dementia

Prevention
-

Exercise


Adult Change in Thought (ACT)
Study


Persons
who exercised 3 or more times a week had a
relative hazard of 0.68

(CI, 0.48 to 0.96) for developing
dementia compared with those who exercised fewer
than 3 times per
week


32% risk reduction in
developing dementia


Dementia

Prevention
-

Cognitive Training


Advanced Cognitive Training for Independent and
Vital Elderly (ACTIVE) Study
(Willis SL, JAMA 2006)


Randomized, single blinded, , multi
-
center, 4 group
design


5 year longitudinal study


Treatment arms


Control (no contact)


Memory training


Reasoning training


Speed of processing training

Dementia

Prevention
-

Cognitive Training


ACTIVE Study


Inclusion: older than 65 years old


Exclusion: substantial functional impairment, major
medical conditions likely to lead to death or functional
decline, dementia, severe sensory impairment


Outcome measures:



a variety of instruments were used to assess the
cognitive effects of each intervention


functional outcomes were assess by independent
activities of daily living (IADLs
)

Dementia

Prevention
-

Cognitive Training


ACTIVE Study


Results
-

2832 patients were randomized


Dementia

Prevention
-

Cognitive Training


ACTIVE Study


Participants in the 3 training arms were statistically
better able to perform IADLs than controls

Dementia

Prevention
-

Cognitive Training


ACTIVE Study


Cognitive training improves cognitive function in
older
adults


The
improvement

from cognitive training lasts at least 5
years from the beginning of the intervention


Improvements in cognitive function can have a positive
effect on daily function
.

Dementia

Prevention


Drugs


Can
acetylcholinesterase

inhibitors and
Memantine

provide
neuroenhancements

in health
individuals?


Not enough data for using these drugs to improve
memory or to prevent dementia
(
Rapantis

D, Pharmacological
Research, 2010)


Dementia

Prevention


Exercise is likely very beneficial


Mentally stimulating activities can have long term
benefits


There is no data to support using
acetylcholinesterase

inhibitors or
memantine

in
healthy adults

Dementia

Atypical Antipsychotics and Dementia


Behavorial

disturbances can be quite problematic
for patients and particularly caregivers


Incidence of hallucinations and delusions


Alzheimer’s Disease


20
-
40%


Lewy

Body Dementia


70
-
90%


Some evidence of efficacy in treating dementia
-
related conditions like delirium
(Cochrane Database of
Systematic Reviews,
www.cochrane.org
)



Dementia

Atypical Antipsychotics and Dementia


Antipsychotics are associated with increased
mortality
(
Rossom

RC, Journal of the American Geriatrics Society, 2010)






Higher rates of comorbidities in treatment cohorts

Dementia

Atypical Antipsychotics and Dementia


What to do about
behavorial

disturbances?


Acetylcholinesterase

inhibitors, SSRI or SNRI,
antiepileptics


Non
-
drug therapy


music therapy, hand massage,
gentle touch, physical activity, reality orientation,
reminiscing


Minimize use of atypical antipsychotics


Psychotic
symptoms that potentially endanger the
patient,
caregiver,
or family


Discuss risk with family



Dementia

Take Home Points


Need a low threshold for screening for dementia, but
be aware of diagnoses that mimic dementia


Many screening instruments


pick one (or two) and
understand the performance characteristics


High dose Donepezil may provide marginal benefit but
side effect risk does increase


Exercise and cognitive training are likely helpful in
preventing dementia and delaying progression


Minimize atypical antipsychotics in managing
behavior disturbance in demented patients


Care for the patient and the family



www.acponline.org

Questions?