Mild and Major Cognitive Impairments
in the Elderly: Diagnostic
Considerations and Implications for
Capacity
David Loewenstein PhD, ABPP/CN
Professor of Psychiatry, Miller School of Medicine,
University of Miami
Growing Older In America
The population of the United
States is growing older and living
longer than ever before
The United States population is
growing older
• In 2000 the number of older adults (age 65 or
above) in the United States was estimated to
be 35 million
• In 2030 it is estimated that there will be
greater than 71 million older adults
• Age is the greatest risk factor for cognitive
impairment and for conditions such as
Alzheimer’s disease (AD)
Cognition and Aging
• Memory and cognition change as we
get older
• Basic processes of change in cognitive
aging:
–Changes in brain structure and
chemistry
Cognitive Abilities Preserved in
Healthy Older Adults (Rubert,
Loewenstein, and Eisdorfer, 2001)
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Attention Span
Remote or Tertiary Memory
Everyday Communication Skills
Lexical, Phonological and Syntactic
Knowledge
• Discourse Comprehension
• Simple Visual Perception
Cognitive Abilities That Decline as a
Function of Aging (Rubert,
Loewenstein and Eisdorfer, 2001)
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Verbal Fluency
Confrontation Naming of Low Frequency Stimuli
Selective Attention
Cognitive Flexibility and Shifting Cognitive Sets
Complex Visuoconstructive Skills
Complex Logical Analysis
Perceptual Speed Tasks
Cognitive Decline in the Older Adult
It is essential to be able to differentiate between
normal aging and mild cognitive impairment
since the latter may represent the earliest
manifestations of early neurodegenerative
disease
What happens?
Dementia: Scope of the Problem
• In 2010 35.6 million older adults across the globe
are living with dementia (predominantly
Alzheimer’s disease)
By 2030- estimated 65.7 million cases
By 2059- estimated 115.4 million cases
• The total estimated worldwide costs of
dementia in 2010 are US $604 billion
• Source: World Alzheimer’s Association (2010)
Earliest Manifestations of AD
• One of the earliest manifestations of AD is
subtle changes in cognitive function
• Memory deficits are typically among the
earliest deficits observed in AD but atypical
presentations have been observed (i.e.,
dysexecutive function, language disturbance,
spatial deficits)
GOALS OF THIS PRESENTATION
1) To become familiar with the definitions of dementia
and mild cognitive impairment (MCI) as contrasted
by the normal aging process
2) Know the etiological considerations (e.g.
Alzheimer's disease) that may underlie cognitive
impairment in the elderly
3) Examine types of cognitive domains that may be
affected in older age (e.g. memory, executive
function and problem-solving, language)
4) Explore how cognitive impairment may affect
decision-making capacity
Let’s Try to Keep those Memories
DSM-IV Criteria for Dementia
• A. The development of multiple cognitive deficits
manifested by both
• 1) memory impairment
• 2) one or more cognitive disturbances (aphasia,
apraxia, agnosia, disturbance in executive
function)
• B. Cognitive deficits cause significant impairment
which represents decline in social and
occupational function
• C. Deficits do not occur exclusively during the
course of a delirium
Alzheimer’s disease
Over 5.5 million people in the United
States are currently afflicted with
Alzheimer’s Disease
Greatest risk factor is age (Risk at 85
Years of Age as High as 35%-50%)
There is presently no cure, only mild
amelioration of symptoms
Probable ALZHEIMER’S DISEASE:
CLINICAL DIAGNOSIS- NINCDS-ADRDA
Criteria (McKhann et al., 1984)
• Dementia
• Diagnosis of exclusion (Approximately 85% accuracy)- Rule
out other disorders, such as stroke, Parkinson’s, and
‘reversible’ conditions, such as drug side-effects
• Clinical features: -Onset is insidious, course is gradually
progressive; memory deficits early; depression often early
– Behavioral symptoms such as delusions, agitation and
wandering commonly occur later
– Average duration is 8-10 years, with great variation (1 to
25 years)
NEUROPATHOLOGY OF ALZHEIMER’S
Plaques
Tangles
AD and the Brain
Beta-amyloid Plaques
1.
Amyloid precursor protein (APP) is the
precursor to amyloid plaque.
1. APP sticks through the neuron
membrane.
2.
3.
2. Enzymes cut the APP into fragments
of protein, including beta-amyloid.
3. Beta-amyloid fragments come together
in clumps to form plaques.
In AD, many of these clumps form,
disrupting the work of neurons. This
affects the hippocampus and other areas
of the cerebral cortex.
Slide 17
AD and the Brain
Neurofibrillary
Tangles
Neurons have an internal support structure partly made up of
microtubules. A protein called tau helps stabilize microtubules. In AD,
tau changes, causing microtubules to collapse, and tau proteins clump
together to form neurofibrillary tangles.
Progressive Atrophy of ERC & HPC
Young
Aged (control)
MCI
Mild AD
Sagittal MRI: Progressive HPC/
Amygdala Atrophy
[11C] PIB and PET:
In Vivo Imaging of β-Amyloid Plaques
Axial
Sagittal
PIB = Pittsburgh compound-B; PET = positron emission tomography. Image courtesy of William E. Klunk, MD, PhD, and Chet Mathis, PhD.
Source: Klunk WE et al. Ann Neurol. 2004;55:306-319.
22
Prediction of Progression of MCI Based
on amyloid imaging using PIB
82% of 11 C-PIB positive subjects with
MCI progressed to AD in three years
Okello A, Koivunen J, Brooks DJ, et al. Conversion of
amyloid positive and negative MCI to AD over 3
years: An 11C-PIB PET study Neurology 2009
Amyloid Plaques Are Not Seen Only in
Clinical AD
Significant Amyloid Plaques Are Seen Postmortem in Older
Nondemented Subjects
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27% (age ≥ 75 years; Price & Morris, 1999)
45% (age ≥ 66 years; Hulette CM et al, 1998)
29% (age ≥ 65 years; Tomlinson BE et al, 1968)
34% (mean age, 85 years; Katzman R et al,
1988)
• ~33% (age ≥ 47 years; Braak & Braak, 1991)
Sources: Price JL, Morris JC. Ann Neurol. 1999;45:358-368.
Hulette CM et al. J Neruopathol Exp Neurol. 1998;57:1168-1174.
Tomlinson BE et al. J Neurol Sci. 1968;7:331-356.
Katzman R et al. Ann Neurol. 1988;23:138-144.
Braak H, Braak E. Acta Neuropathol (Berl). 1991;82:239-259.
COULD THOSE WITH NORMAL COGNITION
ACTUALLY HAVE EARLY AD DUE TO COGNITIVE
RESERVE?
• Alzheimer’s Pathology is seen on autopsy
among 30% of subjects who are not
cognitively impaired in their lifetime.
• This raises the possibility that those with high
cognitive reserve may be able to handle
increased amyloid load and subsequent early
neurodegeneration without exhibiting
symptoms
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FACTORS THAT INCREASE THE PROBABILITY
THAT MCI REPRESENTS EARLY ALZHEIMER’S
DISEASE
Atrophy of the hippocampus and particularly
the entorhinal cortex
PET Scan amyloid imaging or FDG
CSF levels of AB 42 and tau
Homozygous for the ApoE allele (4/4) or
Heterozygous for the ApoE allele
Vascular Dementia: L Frontal Infarct
Microvascular Disease of the Brain
NOT ALL MCI REPRESENTS ALZHEIMER’S DISEASE
• Neuropsychologist Must Insure That Sensory Deficits (Hearing and
Vision Loss) Are Not Mistaken for MCI
• Anxiety/ Depression/ Stress and Cultural Factors Need To Be
Accounted For With Regards To Impact On Cognitive Performance
• Degenerative: Lewy Body Disease; Fronto-Temporal Dementia
• Vascular: Strokes, TIAs, Vasculitis
• Toxic/ Metabolic/Endocrine (Drugs, Alcohol, Thyroid)
• Space Occupying Lesions (Tumors, Subdural Hematomas
Hydrocephalus)
Therapeutic Implications of Disease Course
Normal
Prodromal
Prevent
Onset
Cognitive
Function
Slow
Clinical
Dementia
Progression
Treat
Symptoms
& Slow
Decline
Disease Progression
MILD COGNITIVE IMPAIRMENT CRITERIA
(Petersen et al., 2001 – Neurology)
1. Memory complaint, preferably
corroborated by an informant
2. Objective memory impairment
3. Normal general cognitive function
4. Intact activities of daily living
5. Not demented
WHEN IS MCI EARLY ALZHEIMER’S
DISEASE?
• Morris (2001) 100% of MCI patients in
memory disorders clinic progressed to
dementia over a 9.5 year period (84% met
neuropathological pathological criteria for AD)
• Reviewing of epidemiological studies,
reversion rate of MCI to normal is as much as
30% (see Brooks and Loewenstein,2010;
Ganguli et al., In Press)
MILD COGNITIVE IMPAIRMENT
CONVERSION TO DEMENTIA
Conversion to Dementia
50
40
30
Normal
MCI
20
10
0
1
2
3
Year
MCI was expanded by Petersen
(2003) to include non-amnestic and
multiple cognitive domains
The number of persons with MCI in
the US age 70 and above is estimated
to be between 5 and 6 million
Plassman et al Annals of Internal Medicine 2008
WHAT IS THE BEST WAY TO ASSESS
COGNITIVE AND FUNCTIONAL CAPACITY?
• Neuropsychological Testing Supervised by an
Experienced Clinical Neuropsychologist
• Neuropsychology is the Study of Brain
Function Through Cognitive and Behavioral
Testing
What is a Neuropsychologist?
• Generally a PhD or equivalent in Clinical
Psychology
• One Year Clinical Internship with Primary
Emphasis in Neuropsychology
• One to 2 Year Post-doctoral Fellowship in
Neuropsychology
PURPOSES OF NEUROPSYCHOLOGY
• To assess whether there is a cognitive deficit
• To determine the nature and extent of cognitive
impairment (i.e., memory, language, executive
function)
• To determine how these cognitive impairments
relate to diagnosis of brain disease (more sensitive
than neuroimaging in many conditions)
• To plan for treatment and/or remediation
REAL LIFE APPLICATIONS OF
NEUROPSYCHOLOGICAL TESTING
• Treatment plan after head injury or stroke
• Determine whether there are subtle cognitive
deficits ( surgeon with aneurysm clipping)
• Determining capacity to return to work
• Diagnosis of early neurodegenerative disease
from pure affective or anxiety disorders
affecting cognition
Ms. B
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Referred for Evaluation
3rd Grade education
Depressed
Sister is sure that she is having significant
memory deficits, brother is sure that she is
normal, children are not sure
• Does she have early Alzheimer’s disease?
Advantages of Neuropsychological Testing
• Objective
• Compared to Age and Education Related
Normative Data
• Patterns of Strengths and Weaknesses can
give information about diagnosis and
treatment
Domains of Function Assessed By the
Neuropsychologist
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MEMORY
LANGUAGE (Expressive and Receptive)
VISUOSPATIAL SKILLS
EXECUTIVE FUNCTION
ATTENTION
PROCESSING SPEED
SENSORY MOTOR SKILLS
Anatomy of Memory
Bilateral damage to
the hippocampus
results in anterograde
amnesia (Patient H.M.)
Three Stages of Memory
• Stage 1 - Sensory Memory is a
brief representation of a stimulus
while being processed in the
sensory system
• Stage 2 - Short-Term Memory
(STM) is working memory
– Limited capacity (7 items)
– Duration is about 30 seconds
• Stage 3 - Long-Term Memory
(LTM) is large capacity and long
duration
TYPES OF TESTS THAT ARE GIVEN
• Tests of Learning Over Multiple Trials (Serial
Position effects, learning curves, immediate
versus delayed recall, recognition memory)
• Memory for Passages (Immediate and
delayed)
• Visual Reproduction (Immediate and delayed)
Items To Be Recalled On an Object Memory
Test
Language
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Confrontation Naming (Boston Naming Test)
Semantic Fluency (Animals, Fruits, Vegetables)
Letter Fluency
Reading, Repetition, Writing, Calculations
Receptive Language (Token Test, Simple and
more complex commands)
Visuospatial Skills/Praxis
• Block Design
• Object Assembly
• Copying simple and more complex geometric
designs
Executive Function
• Abstract Reasoning (Similarities)
• Concept Formation and Shifting Cognitive Sets
(Wisconsin Card Sorting Test, Stroop Color
Word Interference, Trailmaking Test)
Attention
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Span (Digits Forwards and Backwards)
Vigilance (Continuous Performance Test)
Divided Attention
Visual Tracking
Auditory Tracking
Sensory/Motor
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Grooved Pegboard
Finger Tapping
Grip Strength
Finger Gnosis
Sensory Perceptual Examination
Comprehensive Neuropsychological
Assessment
• Aids in Accurate Diagnosis
• Helps Clinician Understand Strengths and
Weaknesses (Deficits in certain aspects of
memory and executive function can affect
compliance with treatment)
• Helps establish a baseline to monitor change
over time
• Helps with treatment and remediation
NEUROPSYCHOLOGY AND THE
OLDER ADULT
Two Important Premises in Understanding
Cognitive Decline in the Elderly
1) Significant Cognitive Decline is not an
Invariable Consequence of Normal Aging
2) Increasing Age is a Risk Factor For
Degenerative Brain Disorders Which May
Affect Cognitive Function
Our laboratory is involved In developing tests
that are
a) Sensitive to the earliest changes associated
with neurodegenerative disease
b) Are culturally and educationally fair
c) Address real world memory deficits (i.e.,
prospective memory-remembering to
remember an intended action)
Semantic Interference Test (SIT)
Loewenstein, et al., (2004) Journal of the
International Neuropsychological Society (1)
91-100.
Sensitivity and Specificity of the SIT in the early
Detection of MCI-AD
MCI-AD
Sensitivity= 84.6%
Normal Elderly Specificity= 96.2%
Pre-MCI States and Progression To MCI or
Dementia Over a 2-3 Year Follow-up
(Loewenstein et al., 2010)
Initial DX
No Progression
Progression to
MCI
Progression to
Dementia
Total
Progression
Normal
96.3%
3.7%
0%
3.7%
Pre- Amnestic
MCI+ (N=48)
83.3%
16.7%
0%
16.7%
Pre-Amnestic
MCI ++(N= 18)
61.1%
27.8%
11.1%
38.9%
Pre- Amnestic
MCI Clinical
(N=41)
78.0%
17.1%
4.9%
22.0%
When should someone be referred for
neuropsychological assessment
• There is concern about cognitive changes
related to underlying brain disease
• Separating cognitive effects of depression and
anxiety disorders from underlying cerebral
dysfunction
• To determine cognitive strengths and
weaknesses that may affect treatment
adherence and compliance
Competence and Capacity
• Competency or competence indicates that the
person has the capacity to perform a specific
action
• Capacity is the ability to perform in a specific
situation with the appropriate appreciation to
behave in one’s self interest
Competence and Capacity
• Needs to be assessed with regards to a
specific task or set of tasks
• Writing a will (testamentary capacity) is
different than managing a restaurant or an
apartment complex
How Does Cognitive Function Impact
Upon Decision Making?
• 1) Knowledge of immediate and delayed
consequences of actions
• 2) Appreciation of whether one’s self interest
will be served or hurt by an action or action(s)
• 3) Cognitive slowing, attentional deficits and
impairments in judgment or comprehension
can lead to misunderstanding of potential
risks and benefits and impair decision-making
CASE EXAMPLES
• Donald runs a large family business. The
family notices memory personality changes.
• He insists on making all major decisions even
though his wife and his sons who work in the
business have noticed that he has made
business dealings without their knowledge
that threatens the financial foundations of the
company .
CASE EXAMPLES
• Ruth is accompanied by two daughters. Both
are very upset that she has made a recent
change in her will naming a young man that
she met at church as beneficiary of her estate.
• She has been making increasingly large
purchases at a home shopping network that
has cost tens of thousands of dollars.
CASE EXAMPLES
• George has had three automobile accidents
where he has insisted that the other person is
at fault and there were known witnesses. The
family notices that he has been driving
erratically and forgetting to take essential
diabetes and hypertension medicines. He
refuses any assistance.
CASE EXAMPLES
• A general surgeon shows up for consultation
because he is bored with retirement and
wants to return to limited practice. He wife
notices some minor memory deficits that she
wants evaluated.
• Results suggest a mild to moderate dementia
with impaired memory judgment and spatial
skills.
CASE EXAMPLES
• Mary comes in for evaluation quite concerned.
Her estranged daughter is questioning her
capacity to make decisions about her finances
and engage in medical decision-making about
her cancer.
Major Issues
• Lack of memory ability - affects ability to a)
conduct business; b) leads to errors that
jeopardizes finances; c) endangers person or
property (e.g., non-payment of rent, leaving the
stove burning, failure to take required
medications)
• Lack of judgment- a) decisions that put person
and property at risk; b) inability to properly
understand risks versus rewards; c) immediate
versus delayed consequences; d) subject to
undue influence
Things to Be Aware of in Working With
Older Adults
• Lack of auditory or visual acuity may affect cognitive
processing of information. If an individual does not hear
correctly on telephone, decision making may be impaired.
• Need to present information where a) redundancy is built
in, b) font and volume of speech is friendly to older adults,
c) multimodal presentation of material; d) checks to
understand correct comprehension of material and options
• Need to check person’s understanding of a) potential
decisions and their potential short-term and long-term
impacts; b) how potential consequences works for and
against a person’s self-interest; c) decisions are being made
freely without coercion.
SOME MORE THOUGHTS ON
COMPETENCY
• Competency is a legal rather than a medical term
• Cognitive impairment does not necessarily mean
loss of capacity or competency in a specific area
• Competency is specific to specific areas (i.e.,
finances, medical decision-making)
• Need to gather the most effective data on
strengths and weaknesses. Often professionals
make judgments on competency without proper
skill sets or experience.
Best Evaluation For Cognitive And Skills
Deficits in Older Adults
• Highly trained and experienced
neuropsychologists
• Experienced and trained behavioral
neurologists or geriatric psychiatrists who give
a through neurocognitive evaluation
ISSUES
• 1) Should persons have an independent
neuropsychological evaluation to serve as a baseline to
assess future decline?
• 2) How do we judge that person has the capacity to
truly understand options and what works in long-term
and short-term interests?
• 3) How do we insure that decisions made in later life
are consistent with the person’s previously stated
wishes and that changes in decisions do not reflect
cognitive difficulties, psychiatric disturbance or undue
influence?