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The American College of Osteopathic Family Physicians designates the lectures and workshops for Category 1-A credits on an hour-for-hour basis, pending approval by the AOA CCME, ACOFP is not responsible for the content.
ACOFP / AOA’s 122nd Annual Osteopathic Medical Conference & Exposition
OCTOBER 7 - 10PHILADELPHIA, PENNSYLVANIA29.5 Category 1-A CME credits anticipated
OMED 17®
Joint Session with ACOFP and Cleveland Clinic: Managing Chronic Disease
Dementia and Mild Cognitive Impairment: Evaluation, Management, and When to Refer
Jagan Pillai, MD, PhD
10/5/2017
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Jagan A PillaiNeurologist
Center for Brain Health
Dementia &Mild Cognitive Impairment:Evaluation, Management
and When to refer
Learning Objectives
1. Know current guidelines for evaluation and diagnosis of Mild Cognitive Impairment (MCI) and dementia
2. Keep abreast of new developments on the use of biomarkers in helping ascribe their underlying etiology
3. Know basics of management of MCI and dementia and what can a specialist provide in addition
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Case 1. Mr. Mac
• 72 year man for evaluation of memory loss.
• Visit was prompted by his increasing difficulty in retrieving names when working as a tour guide.
• Still handles all his activities of daily living (ADLs) but he is loosing track of what he is doing when completing a task.
• Difficulty with managing schedules and more hesitant driving.
• More noticeable changes over last 2 years.
Case 2. Mrs. CS
• 64 year old right handed woman with a 2 year history of word finding difficulty.
• Clinical and neuropsychological assessments confirmed a profound anomia and relatively preserved function in other cognitive domains.
• MRI brain showed evidence of medial and anterior temporal lobe atrophy with greater left sided emphasis.
• A clinical diagnosis of Alzheimer’s disease was made .
• On longitudinal follow up over two years she noted no significant changes in her functional ability
• Referred for a second opinion.
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Case 3. Ms.Min
• 58 year old right handed woman has difficulty driving to work.
• Has become lost on her way to work where she has been a school teacher for 35 years.
• More anxious while driving, had 2 fender benders last month.
• She handles work very well in her day job and at home.
• She has noted that her hand writing is a more scraggly and has had more bumps and trips but no falls
Key Point
• No single point in history• No single cognitive assessment
• No single neuroimaging result
• No single biomarker result
can definitely make a diagnosis of normal cognition, MCI, dementia or a neurodegenerative disease
• More than one of the above have to taken together within context to help make an individual diagnosis
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Diagnosis often depends on 3 key answers
1. What lobes/parts of the brain are affected ?
[Frontal, temporal, occipital, parietal, subcortical]
2. What is the severity of the problems?
[ is the person capable of taking care of themselves independently..can they do their ADLS and IADLS or not?)
3. What is the underlying etiology?
[Normal ageing, Alzheimer's, Frontotemporal, Lewy body disease, Normal pressure hydrocephalus, Autoimmune etc.]
1. What lobes/parts of the brain are affected ?
From Front. Integr. Neurosci., 12 September 2013
1. Is it Cortical, Subcortical or both?
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Modified from qbi.uq.edu.au
Occipital: Vision
Left Temporal: Object Naming
Prefrontal:AttentionJudgment,OrganizingPlanning
Orbitofrontal:Social Graces
Parietal:Spatial judgmentMotor coordinationCalculation
Prefrontal cortex (PFC) early changes
Left Temporal
Parietal and PFC
PFC later changes
Hippocampal vs PFC
Left Temporal PFC early change
PFC early change
Montreal Cognitive Assessment
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Hippocampus: Delayed Recall [Episodic memory]
Different from deficits in:Immediate RecallRecall With Cues
in Frontal subcortical lesions
2. What is the severity of the problem?
• Dementia
• Mild Cognitive Impairment
• Within age related norms
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What constitutes dementia?
Not every one with memory loss is demented
23% of community subjects >70yrs had hippocampal dysfunction
but not demented.
(Small et al, 2002)
National Institute of Aging/ Alzheimer s Association NIA‐AA 2011 criteria for Dementia
Cognitive or behavioral symptoms that:
• Represent a decline from previous levels of functioning
• Interfere with the ability to function at usual activities; • Are not explained by delirium or major psychiatric disorder; and
• The cognitive or behavioral impairment involves a minimum of two of the following domains:
• Impaired ability to acquire and remember new information.• Impaired reasoning and handling of complex tasks, poor judgment• Impaired visuospatial abilities.• Impaired language functions • Changes in personality, behavior, or comportment
McKhann et al, 2011
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Frequency of Dementia Types
(Barker et al, ADAD 2002; 16: 203-212)N = 382
VascularLewy Body FrontotemporalHippocampal sclerosisAutoimmunePrionAlcohol relatedNormal pressure hydrocephalus
Dementia etiologies by age at onset and Progression Dementia etiologies by age at onset and Progression
(<65yrs at onset of symptoms)
‐ Young onset Alzheimer's
‐ Fronto‐temporal dementia syndromes
‐ Huntingtons disease
‐ Prion diseases
‐ Korasakoffs amnesia
‐ Large strokes
‐ Other syndromes(Wilson’s disease,Metachromatic leukodystrophy, Adrenoleukodystrophy, Kuf’s disease, adult polyglucosan body disease, Cerebrotendinousxanthomatosis, Mitochondrial disorders,Fahrs disease)
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Between 65‐80yrs
‐ Alzheimer's disease
‐Multi infarct vascular disease
‐ Lewy Body dementia
‐ Fronto‐temporal dementia syndromes
‐ Parkinson's disease dementia
Dementia etiologies by age at onset and Progression
Dementia etiologies by age at onset and Progression Dementia etiologies by age at onset and Progression
(Over 85yrs
‐ Mixed dementia pathology
‐ Multi infarct vascular dementia
‐ Alzheimer's disease
‐ Cerebral amyloid angiopathy
‐ Hippocampal sclerosis dementia
‐ Lewy Body dementia
‐ Parkinsons disease dementia
‐ Argyrophiic grain disease
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Mild Cognitive Impairment (MCI)
MCI is an often an unstable diagnosis
• 16% of MCI reverted back to normal or near‐normal ~1 year later
• 20% progress to dementia
• No clear difference with age on onset
(Kopesell & Monsell, 2012)
MCINormal Dementia
NIA‐AA 2011 criteria for MCI—Criteria for the clinical and cognitive syndrome
1. Concern regarding a change in cognition
2. Impairment in one or more cognitive domains
3.Preservation of independence in functional abilities
4. Not demented
Albert et al, 2011
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How to judge if MCI or dementia?How to judge if MCI or dementia?
1. What is the likely baseline performance for the patient?
2. Are there possible reversible factors masking performance level?
3. Is independence in functional abilities of daily life affected?
MCI Dementia
What is the likely baseline performance for the patientWhat is the likely baseline performance for the patient
• Age
• Education
• Previous functional status
• Physical activity level
• Previous medical comorbidites and risk factors
Factors mediating cognitive and brain reserve
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Are there possible reversible factors masking performance level?Are there possible reversible factors masking performance level?
Is this a normal aging or MCI patient being stressed to worse performance of dementia?
‐Medical illness
‐Medications
‐Significant psychological stressors
‐Depression
‐Substance abuse and toxicities
MCI etiologiesMCI etiologies
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MCI etiologiesMCI etiologies
NIA‐AA 2011 criteria for MCI—likely from AD
• Acknowledges Mild cognitive impairments related to AD that does not reach threshold of dementia
• More specifics on distinguishing AD from non AD dementia
• Incorporation of biomarkers of the underlying disease state
Alberts et al, 2011
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How to judge if MCI or normal cognition with ageHow to judge if MCI or normal cognition with age
1. What is the likely baseline performance for the patient?
2. Based on our knowledge of different rates and degree of decline across different cognitive domains
MCINorma
l
Crossectional
Longitudinal
Hedden & Gabrieli,2004
Verbal ability
Verbal ability
Perceptual speed
Perceptual speed
Rates and degree of declineacross different cognitive domains
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Cognitive skills mostly stable with age
• Autobiographical memory
• Emotional processing (performance in attributing appropriate mental states to others)
• Implicit memory (sense of having previously encountered task before influencing performance…feeling of familiarity in influencing good guesses better than chance)
• Orientation to person, place and season
• Verbal ability
Any abnormality here is likely to be pathological
Less likely NORMAL AGING IF >1 within each domain or 4 domain errors made
Quick RULE OF THUMB
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Assessment of Dementia and MCI• History
• Course, risk factors
• Mental status examination
• Neuropsychiatric assessment (hallucinations,
delusions, agitation, depression)
• Neurologic/medical examination
• Laboratory studies (Thyroid function panel, Vitamins
B1, B12, MMA, Folate, Sed rate, RPR)
• Lumbar puncture and CSF evaluation if atypical
features
• Neuroimaging
Biomarkers currently clinically used for AD diagnosis
• Hippocampal and medial temporal lobe atrophy more than expected for age
• CSF low Aβ (<190pg/ml) and high Tau (>90pg/ml)
Tau/ Aβ Ratio >0.5, sensitivity and specificity values 85.7 and 84.6%,
• FDG PET noting hypometabolism in posterior cingulate, bi parietal and temporal regions
• Amyloid PET
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Normal MCI due to AD AD dementia
Biomarker: Hippocampal atrophy
Jack et al, 2010
In patients with Alzheimer disease and mild dementia,sensitivity was 77%, and specificity, 80%
(Jack et al, 1997)
Cerebrospinal fluid biomarker in autopsy confirmed AD subjects
• AD
O Normal
(Shaw et al, 2009)
Tau
Pg/ml
Aβ Pg/ml
Biomarker: CSF
t‐tau/Aβ1‐42 ratioSensitivity 85.7%Specificity 84.6%
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Mild Alzheimer disease may be more difficult to detect than moderate or severe disease
FDG PET is more sensitive than hippocampal atrophy and CSF t‐tau/Aβ1‐42 ratio But less specific than them both for AD
Klunk et al. (2004)
Biomarker: FDG PET
Sensitivity 94%Specificity 73%
(Salmon et al, 1996)
Normal MCI due to AD AD dementia
Biomarker: Amyloid PET
(Jack et al, 2010)
Florbetapir F 18: FDA approved in April 2012
Sensitivity: 92% Specificity 100% at 2 years prior to autopsy
(Clark et al, 2012)
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I initially seek
• Progressive clinical history including family history
• Office cognitive evaluation (MoCA)
• Cognitive and functional deficits including episodic memory loss
• Neurological and behavioral evaluation including depression
• Blood tests for reversible dementias
• MRI brain/CT head
• Neuropsychology evaluation if warranted
My practice overview
‐Educate patient and family members on what is being done during evaluation‐Understanding etiology of cognitive and functional decline‐Judgment of patients capabilities to handle independent life style safely‐Evaluate neuropsychiatric and depression changes‐IF MCI, reasons for MCI diagnosis and the potential reversibility of this and the need for follow up evaluation‐Lifestyle management of cognitive symptoms (Structured program vs patient or family initiated)‐Safety and medical decision making skills‐Medical management of dementia
What can we offer for cognitive improvement and maintaining functional status in both normal and pathological states?
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Basic management of MCI and dementia
1. Reversible dementia work up2. Neuroimaging3. Vascular risk factor check and depression screen4. Education of family on nature of diagnosis prognosis5. Tasks that improve working memory,6. Trial of AChE inhibitors/ NMDA partial antagonists if patient desires it7. Follow up to evaluate progression8. Discussion on medical decision making9. Driving evaluation if still driving10. Fall and safety precautions11. Community and social services available for patient and caregiver
support
What can a specialist provide in addition
• Confirm diagnosis of a etiology in atypical and young onset cases
• Provide guidance for patient and family in regard to
a. Medication choice (DLB, PDD, CBD, autoimmune etc)
b. Less common etiologies follow up
c. Options on clinical trials
d. Cognitive and occupational therapy options
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Case 1. Mr. Mac
• 72 year man for evaluation of memory loss.
• Visit was prompted by his increasing difficulty in retrieving names when working as a tour guide.
• Still handles all his activities of daily living (ADLs) but he is loosing track of what he is doing when completing a task.
• Difficulty with managing schedules and more hesitant driving.
• More noticeable changes over last 2 years.
23
16 years of education
MOCA 23/30Deficits in phonemic fluencyMissed all in delayed recall got back only one with multiple choice cues.
Hippocampal
PFC ch
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Severe Hippocampal atrophy and delayed recall deficit
Diagnosis often depends on 3 key answers
1. What lobes/parts of the brain are affected ?
Hippocampus
2. What is the severity of the problems?
Can they do their ADLS and some difficulty with IADLs
3. What is the underlying etiology?
Patient did not want to pursue additional tests
Diagnosis :
Amnestic MCI
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Case 2. Mrs. CS
• 64 year old right handed woman with a 2 year history of word finding difficulty.
• Clinical and neuropsychological assessments confirmed a profound anomia and relatively preserved function in other cognitive domains.
• MRI brain showed evidence of medial and anterior temporal lobe atrophy with greater left sided emphasis.
• A clinical diagnosis of Alzheimer’s disease was made .
• On longitudinal follow up over two years she is no longer working but noted no significant changes in her functional ability at home
• Referred for a second opinion.
21
16 years of education
MOCA 21/30Deficits in phonemic fluency, cube copy, abstraction, namingMissed 4 in delayed recall but got back 3 with cues.
Left Temporal
Hippocampal vs PFC
PFC ch
PFC earlychange
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MRI Brain: FLAIR sequence:Left predominant temporal pole and temporal lobe atrophy
CSF High Aβ not consistent with Alzheimer's)
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Diagnosis often depends on 3 key answers
1. What lobes/parts of the brain are affected ?
Left temporal lobe, frontal lobe
2. What is the severity of the problems?
Can they do her ADLS but cannot do IADLs
3. What is the underlying etiology?
No positive Abeta biomarker therefore likely Frontotemporaldementia under the clinical context
Diagnosis :
Likely Fronto‐temporal dementia: Semantic dementia subtype
Case 3. Ms.Min
• 58 year old right handed woman has difficulty driving to work.
• Has become lost on her way to work where she has been an French school teacher for 35 years.
• More anxious while driving, had a 2 fender benders last month.
• She handles work at home but difficulty at work in school and slipped at work.
• She has noted that her hand writing is a more scraggly and has had more bumps and trips but no falls
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20
18 years of education
MOCA 20/30Deficits in Trails B, Cube and Clock drawingSerial sevensMissed one in delayed recall
Parietal and PFC
Parietal
Prefrontal cortex (PFC)
FDG PET Brain: Hypometabolism of bilateral parietooccipital, posterior temporal lobes and cingulate gyrus,
Amyloid PET Brain: Positive for Abeta amyloid
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Diagnosis often depends on 3 key answers
1. What lobes/parts of the brain are affected ?
Parietal, mild frontal
2. What is the severity of the problems?
Can they do her ADLS but cannot do IADLs
3. What is the underlying etiology?
Positive amyloid PET supportive of Alzheimer's diease
Diagnosis :
Alzheimer's dementia: Posterior cortical atrophy variant
10 Dementia Performance Measures
1. Staging of dementia2. Cognitive assessment3. Functional status assessment4. Neuropsychiatric symptom assessment5. Management of neuropsychiatric symptoms6. Screening for depression measures7. Counselling regarding safety concerns8. Counselling regarding driving risks9. Palliative care counselling and advance care planning10. Caregiver education and support
Dementia Measures Work GroupAm J Occup Ther. 2013; 67(6): 704–710
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Thank You!