Case Example
Mild Cognitive Impairment
Cliff Singer, MD
Adjunct Professor, University of Maine
Chief, Geriatric Mental Health and Neuropsychiatry
Acadia Hospital and Eastern Maine Medical Center
Bangor, Maine
• 80 year old WF in excellent health
• Her family notices word-finding struggles,
some geographic confusion and repetition
• PCP, persuaded by family to assess.
• MMSE = 27. “She’s fine.”
• One year later, family more concerned.
• PCP reluctantly agrees to re-assess.
MMSE=29. “She’s fine.”
• Patient. “I told you!”
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Memory: Age Effects
Objective
Description
Age effects
information for rapid
access
moderate decrease
-implicit
instinct
increases
-procedural
know-how
increases
-autobiographical
personal knowledge
preserved
-semantic
general knowledge
increases
-episodic
events
decreases: most
affected
-prospective
remember to do
something
decreases
Working memory
• To improve your ability to answer these
questions regarding subject memory
impairment:
Remote memory
– “Is this dementia?”
• Answers: No, not sure, not yet or yes
Recent memory
– “Is this Alzheimer’s disease?”
• Answers: No, possibly, partly or probably
Cognitive Changes
Salthouse TA. Current Direct Psychol Sci 2004; 13:4:140-44
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Natural History of Cognitive Change
Normal Aging
MCI
Dementia
Noticeable symptoms
Diagnosis
Time
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Hypothetical Progression of AD
What’s Normal?
Jack CR et al. Lancet Neurology 2010
• What’s his name?
• What’s that called?
• Where did I park?
• Where did I put those?
• Did I tell you this already? Yes.
• Did I ask this already? Yes.
• Did you tell me this already? Yes.
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Progression of Cognitive Changes
What’s Not Normal
• Getting lost in a familiar place.
• Not being able to follow a directions/recipe
• Telling the same story more than twice
without asking.
Aging
MCI
Dementia
Recall and
learning
Executive
Intact
Impaired
Impaired
Intact
Intact
Dependent
Reasoning
Abstract
Abstract
Concrete
• Asking the same question more than twice.
Navigation
Intact
Transition
Impaired
• Losing interest in conversation, leaving home,
hygiene, other people
Speech
Mild WFD
Transition
Anomia
Behavior
Normal
Changing
Changed
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Memory Complaints in Primary Care
Guidelines for Dementia Screening:
American Geriatric Society
• Waldorff FB et al. 2012: 24% > 65 reported
subjective memory complaints (SMC).
• Snitz BE et al. 2008: SMC correlated with
objective memory impairment (OMI) except
either w/depression (false +) or more severe
impairment (false -)
• Benito-León J et al. 2010: Depression was
stronger predictor of SMC than OMI.
• Routine cognitive screening not
recommended beyond questions about:
– Short term memory
– Function
• Money management, driving, medication
management, safety in the home
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AGS Guidelines for Diagnosis
Alzheimer’s Assoc. Recommendations
www.americangeriatrics.org
Cordell CB et al. Alz Assoc 2013; 1-10
• If problem is suspected based on
screening question, or patient/family
complaint:
• Alzheimer’s Association advisory group does
recommends routine screening
– Incorporate into Medicare Annual Wellness Visit
– CI missed in 27-81% of visits
– SMC sensitivity of 43% in dementia and only 37%
in MCI (Mitchell AJ 2008)
– Structured tools improve detection: 83% vs. 59%
(Borson S et al. 2006)
– Assess cognition with validated instrument
– Document cognitive domains affected
– Document functional impairment
– Document time course and progression
– R/O delirium and depression
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Advisory Group Recommendations
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UNE GEC Dementia
Conference
www.alz.org/healthcareprovider
Cordell CB et al. Alz Assoc 2013; 1-10
• 2-step process:
– Screen with either Mini-Cog or GPCOG
– Positive screen or clinical suspicion:
• MoCA or SLUMS
• labs, depression screen, neurologic exam or
refer to dementia expert (geriatrician, geriatric
psychiatrist, neurologist, neuropsychologist)
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Detection of MCI
Why Diagnose Cognitive Impairment?
• Screening recommendations based on
sensitivity of instruments for dementia
• Detection of more subtle decline that
validates SMC associated with
increased risk for eventual progression
to dementia is more challenging
•
•
•
•
•
•
•
•
•
People want to know
Prognosis (at higher risk for dementia)
Un-diagnose dementia and de-stigmitize
Secondary prevention (delirium, excessive disability)
Medication management
Financial management and exploitation
Driving safety
Increase motivation for primary/secondary prevention
Clinical trial information (ClinicalTrials.gov)
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Why not diagnose MCI?
Mini-Cog
Lingler JH et al. The Gerontologist 2006; 46:6:791-800
• Range of positive and negative emotions
accompany MCI diagnosis
• Stigmatize (thought of as having dementia)
• Ambiguity of prognosis may create
problems for future planning
• Time constraints
•
•
•
•
•
3-word recall and clock draw test
Pass/fail or 7-point scoring
2-4 minutes administration
Validated across cultures
Good sensitivity for dementia (>80%) but
poor for MCI (55%)
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Mini-Cog Algorithm
GPCOG (www.gpcog.com.au)
Brodaty H et al. JAGS 2002; 50:3:530-534
• Patient assessment of memory, date
and CDT (2-5 minutes)
• Family interview regarding function and
symptoms (1-3 minutes)
• Use of direct assessment and both
patient and caregiver interview of ADLs
is unique and increases sensitivity
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Pfeffer R. et al.
J Gerontol.
1982; 37:3:323-329
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Mild Neurocognitive Disorder: CDR
Informant-based interview to differentiate
aging from dementia
Galvin JE et al. Neurology 2005; 65:559-64
www.alz.org/health-care-professionals/
Scoring:
0-1: Normal cognitive function
2-8: Cognitive impairment
Sensitivity > 84%
Specificity > 80%
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MoCA vs. MMSE
MOCA
(www.mocatest.org)
10-15 minutes
Educational bias
Sensitive enough for MCI
Diagnostic value
Available in 35+
languages
Low-vision (blind) version
In the public domain
Extensive literature
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Nasreddine ZS et al. J Am Ger Soc 2005; 53:695-699
• MoCA (” 26)
– Sensitivity
• MCI=90%
• Mild AD=100%
– Specificity
• Mild AD=87%
• MMSE (” 26)
– Sensitivity
• MCI=18%
• Mild AD=78%
– Specificity
• Mild AD=100%
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MCI Diagnostic Criteria
Cognitive Reserve: MCI vs. Dementia
Peterson R et al. Arch Neurol 1999; 56:303-308
Percent Change Relative to Standard TUG
Singer C and Eden S. Poster Inter Psychogeriatric Assoc, Berlin Germany, October 2015
100
90
80
70
60
50
40
30
20
10
0
• Subjective memory complaint
• Normal ADLs
• Normal general cognition
– MMSE 24-27; MoCA or SLUMS 18-26
Months FWD
(Easy Task)
Months BKWD
(Difficult Task)
Normal
MCI
• Amnestic subtype:
– Abnormal memory for age (lowest 10%)
– Often pre-dementia Alzheimer’s Disease
– Initial report of conversion rate 12-15% per year vs. 1-2% for
those w/normal recall
• “Non-amnestic” forms likely prodrome to other types of
dementia
Dementia
Multi-tasking slows gait in people with dementia.
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DSM-5 Mild Neurocognitive Disorder
Dementia Diagnosis:
Diagnostic and Statistical Manual of Mental Disorders 5th Edition, 2013
McKhann GM et al. Alz & Dem 2011; 7:263-269
•
Evidence of modest decline in one or more cognitive
domains (“multiple domain type”)
– Complex attention, executive function, learning and
memory, language, perceptual-motor, social cognition
•
•
•
•
•
•
Cognitive deficits do not interfere with independence in
everyday activities
Cognitive deficits not occur exclusively during course of
delirium
Cognitive deficits not due to mental disorder
Underlying cause should be specified if possible
Reassess at 6-12 month intervals
Prevalence estimates vary from 7-24% (average 18.9%)
•
•
•
•
•
Cognitive problem interferes w/ function
Decline from previous level of function
Not due to delirium or mental illness
Impairment is validated by testing (MoCA<24)
Impairment is present in • 2 domains:
– New learning and memory, executive, visuospatial,
language, behavior
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DSM-5 Major Neurocognitive Disorder
• Evidence of decline in one or more cognitive
domains from subjective report or testing
• Cognitive deficits are severe enough to interfere
with independence in everyday activities
• Cognitive deficits not occur exclusively during
course of delirium
• Cognitive deficits not due to mental disorder
• Underlying cause should be specified if possible
DSM-5:
Major Neurocognitive Disorder due to AD
• Major neurocognitive disorder is present
• Insidious onset and gradual progression
• Decline in memory and learning and at least one other
cognitive domain
• No evidence of other medical, neurologic or psychiatric
condition to explain the findings
• Or, there is genetic or biomarker confirmation before
dementia develops
Prevalence of Diagnoses
Diagnosis of MCI Due to AD
Feldman H et al. Neuroepidemiology 2003; 22:265-74
Albert MS et al. Alzheimer’s Dementia 2011; 7:3:270-9
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Patient A:
MCI/AD
Patient A: CDR
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Patient B:
Dementia/AD
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Patient B: CDR
From: Cerebrospinal Fluid Levels ofȕ-Amyloid 1-42, but Not of Tau, Are Fully Changed Already 5 to 10 Years
Before the Onset of Alzheimer Dementia
Arch Gen Psychiatry. 2012;69(1):98-106. doi:10.1001/archgenpsychiatry.2011.155
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Date of download: 12/3/2014
CSF Biomarkers
Blenow K et al. Alzheimer’s & Dementia 2015; 11:58-69
• Low Aȕ42 and high T-tau/P-tau: AD “signature”
• Low Aȕ42
– Reduced to 50% of control levels
– MCI: 95% sensitivity to prodromal AD
– May predict decline in cognitively normal
• High tau
– P-tau increased to 200% of control levels in AD
– T-tau not-specific but adds sensitivity to low Aȕ42
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Biomarkers
Aȕ PET: PIB beta-amyloid imaging
agent
Lautner R et al. JAMA Psychiatry 2014; 7:10:1183-91
RED =
maximum
uptake
VIOLET =
minimum
uptake
University of
Pittsburgh
Biomarkers in MCI
Clinical Use of AD Biomarkers
Peterson R et al. J Int Medicine 2014; 275:214-228
Molinuevo JL et al. Alzheimer’s & Dementia 2014; 10:808-17
MCI due to AD
Aȕ markers
Neurodegeneration
Unlikely
negative
negative
Possible
positive
negative
Possible
negative
positive
Likely
positive
positive
• Diagnostic criteria: sensitivity 70.9-87.3% with
specificity of 44.3-70.8% (possible vs. probable)
• CSF markers:
– If all 3 CSF markers are normal, AD is highly unlikely,
regardless of age or APOE genotype
– If all 3 are strongly positive (>10% over cutoff score), AD is
likely
– With ambiguous results, PET or PIB can help clarify
– BUT, until we have disease modifying therapies available
clinically, is it worth doing the tests?
Is Dementia in the Oldest AD?
Non-Amnestic MCI
Haroutunian V et al. Arch Neurol 2008; 65:9:1211-1217
• Vascular
– Small vessel disease typically presents with
frontal/executive signs > memory
• Lewy Body and Parkinson’s Diseases
– Generally show more fluctuations in
cognition, parasomnia, bradykinetic
parkinsonism, slow processing, visual
hallucinations, mood disorders
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Patient C:
MoCA
Patient C CDR
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Psychiatric MCI & Dementia
TBI and EtOH
• Schizophrenia (“dementia praecox”):
• TBI: Persistent impairment may occur with
mild impacts, cognition may improve slowly
with time, but progressive decline also
occurs with single and multiple
concussions (CTE)
• EtOH: Either generalized dementia and/or
amnestic syndrome (Korsakoff’s following
Wernike’s) usually improving with sobriety
over several months, may be persistent
– Frontal-executive dysfunction primarily
• Anxiety disorders
– Memory and attention deficits, fluctuates
• Depression:
– Memory, attention, executive dysfunction, variable
severity (MCI to dementia), fluctuates
– Unmasks latent neurodegenerative dementia
– Early symptom of AD and other dementias
– Accelerates dementia from AD?
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Primary
Prevention
Clinical Plan
• Once MCI is detected:
– Identify underlying causes including meds
– Acknowledge uncertain prognosis
– Counsel cognitive/brain health
– Optimize Rx of comorbid risk factors
*
Patterson C et al. CMAJ 2008;
178:5:548-56
*
• BP, sleep (insomnia and OSA), mood disorders
– Monitor cognition, ADLs and safety at 6-12
month intervals
– Refer to clinical trials if appropriate
* Some RCT data for improving
cognitive function. Chertkow H et
al. CMAJ 2008; 10:1273-85
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Counseling Brain Health
• Generalized
–
–
–
–
–
–
–
Mediterranean diet
Physical and social activity
Sleep
Stress reduction/meditation
Periodic fasting
Moderate alcohol intake
Correct sensory losses if possible
• Specialized
– Cognitive activity
Case Example Follow-Up
AChE Inhibitors in MCI from AD
•
• This is my mother-in-law
• 1 year later, subtle cognitive decline,
varying with fatigue and glucose levels
• Observational diagnosis: early amnestic
MCI
• “Patient” agrees something is wrong.
• Interventions: Some driving restrictions and
enrollment in RCT for MCI 2° AD
Salloway S et al. Neurology 2004:63:4:651-7
– 270 patients, 24 week RCT, donepezil vs. placebo
– No change in primary outcome measures
– But more donepezil-treated patients showed improved
attention, psychomotor speed and total ADAS-cog
•
Doody R et al. Neurology 2009; 72:18:1555-61
– 48 week, RCT, donepezil vs. placebo
– Slight improvement in ADAS-cog, not CDR
– Slight advantage to donepezil on subjective ratings
• Conclusions: Off label and generally ineffective for
MCI from AD.
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“The Husband” by Joseph Mills
He comes every day to eat lunch and sit͒with her in the
sun room. Sometimes he reads͒letters out loud from
their children or friends;͒sometimes he reads the paper
as she sleeps.͒One day the staff makes her favorite
cake͒to celebrate their anniversary,͒and he tells how, to
buy her ring, he worked͒months of overtime at the
factory,͒so she thought he was seeing someone
else.͒"As if I would look at other women͒when I have
Pearl," he says, shaking his head.͒She begins to cry and
tells him, "You're sweet, ͒but I miss my husband." He
pats her hand. ͒"I know," he says, "It's all right. Try some
cake."
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