Transcript Dementia: Diagnosis and Treatment

Dementia: Diagnosis and
Treatment
Debra L. Bynum, MD
Division of Geriatric Medicine
November 2003
Case …
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Mr. Jones is a 72 y/o gentleman brought to you by his daughter for
progressive memory loss. He denies any problems. She reports that
he was an accountant, and is now unable to keep his own check book
straight. He has also had difficulty with getting lost while driving to the
store. His wife died 2 years ago, and he was diagnosed with
depression at that time. In addition, he has HTN and DM. His father
was diagnosed with alzheimer’s disease at the age of 85. On exam,
his BP is 170/90; he is oriented, scores 26/30 on the MMSE (0/3 recall
and difficulty with the intersecting pentagon); he is unable to do the
clockface.
A few months later, his MMSE is 24/30; on exam he has some mild
cogwheel rigidity and a slight shuffling gate, but no tremor. His
daughter reports that he has been having vivid visual hallucinations
and paranoid thought…
Questions
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1. What are some limitations to the MMSE?
2. Is there any association between HTN and
dementia in the elderly?
3. What are the risk factors for dementia?
4. Would apo E testing be of benefit in this case?
5. What type of dementia might Mr. Jones have?
6. What medications should be avoided with this
type of dementia?
Outline
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1. Risk factors and definition of dementia
2. Types of Dementias
3. MMSE and testing
4. Treatment options
Risk factors for dementia
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Age (risk of AD 1% age 70-74, 2% age 75-79, 8.4%
for those over age 85)
Family hx (10-30% risk of AD in patients with first
degree relative with dementia); also cross with
parkinson’s with dementia
Head trauma
Depression (?early marker for dementia)
Low educational attainment?
?hyperlipidemia
?diabetes
Risk factors for AD…
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Gender (confounding in literature – women
more likely to live longer, be older….)
Down’s syndrome
?estrogen (probably not)
?NSAIDS (probably not)
Cognitive decline with aging
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Mild changes in memory and rate of
information processing
Not progressive
Does not interfere with daily function
DSM Criteria
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1. Memory impairment
2. At least one of the following:
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Aphasia
Apraxia
Agnosia
Disturbance in executive functioning
3. Disturbance in 1 and 2 interferes with daily
function
4. Does not occur exclusively during delirium
Activities of Daily Living
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ADLs: bathing, toileting, transfer, dressing,
eating
IADLs (executive functioning):
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Maintaining household
Shopping
Transportation
Finances
Diagnosis of Dementia
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Delirium: acute, clouding of sensorium, fluctuations
in level of consciousness, difficulty with attention and
concentration
Depression: more likely to complain of memory loss
than in those with dementia
Delirium and depression both markers for future
dementia
5% people over age 65 and 35-50 % over 85 have
dementia, pretest probability of dementia in older
person with memory loss at least 60%
Alzheimer’s Disease
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60-80% of cases of dementia in older patients
Memory loss, personality changes, global cognitive
dysfunction and functional impairments
Visual spatial disturbances (early finding)
Apraxia
Language disturbances
Personality changes
Delusions/hallucinations (usually later in course)
Alzheimer’s Disease
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Depression occurs in 1/3
Delusions and hallucinations in 1/3
Extracellular deposition of amyloid-beta
protein, intracellular neurofibrillary tangles,
and loss of neurons
Diagnosis at autopsy
Alzheimer’s Disease
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Onset usually near age 65; older age, more likely
diagnosis
Absence of focal neurological signs (but significant
overlap in the elderly with hx of CVAs…)
Aphasia, apraxia, agnosia
Family hx
Normal/nonspecific EEG
Personality changes
Vascular dementia
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Onset of cognitive deficits associated with a stroke
(but often no clear hx of CVA, more multiple small,
undiagnosed CVAs)
Abrupt onset of sxs with stepwise deterioration
Findings on neurological examination
Infarcts on cerebral imaging (do not over read ct and
mri scans….)
In reality, significant overlap between alzheimer’s
and vascular dementias; 90 y/o likely to have both
based purely on demographics; treatment likely
targets both…
Dementia with Parkinson’s
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30% with PD may develop dementia; Risk
Factors:
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Age over 70
Depression
Confusion/psychosis on levodopa
Facial masking upon presentation
Hallucinations and delusions
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May be exacerbated by treatment
Dementia with Lewy Bodies
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Cortical Lewy Bodies on path
Overlap with AD and PD
Fluctuations in mental status (may appear delirious)
Early delusions and hallucinations
Mild extrapyramidal signs
Neuroleptic hypersensitivity!!!
Unexplained falls or transient changes in
consciousness
Progressive Supranuclear Palsy
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Uncommon
Vertical supranuclear palsy with downward
gaze abnormalities
Postural instability
Falls (especially with stairs)
“surprised look”
Difficulty with spilling food/drink
Frontal Lobe Dementia
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Impairment of executive function
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Initiation
Goal setting
planning
Disinhibited behavior
Cognitive testing may be normal/minimally abnormal;
memory loss not prominent early feature
5-10% cases of dementia
Onset usually 45-65
Frontal Lobe Dementia…
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Focal atrophy of frontal and/or anterior
temporal lobes
Frontal lobe degeneration of the non-AD type
(lack of distinctive histopath findings seen
with AD or Pick’s)
May be autosomal dominant (inherited form
known as frontotemporal dementia)
Pick’s Disease
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Subtype of frontal lobe dementia
Pick bodies (silver staining intracytoplasmic
inclusions in neocortex and hippocampus)
Language abnormalities
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Logorrhea (abundant unfocused speech)
Echolalia (spontaneous repetition of
words/phrases)
Palilalia (compulsive repetition of phrases)
Primary Progressive Aphasia
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Patients slowly develop nonfluent, anomic aphasia
with hesitant, effortful speech
Repetition, reading, writing also impaired;
comprehension initially preserved
Slow progression, initially memory preserved but
75% eventually develop nonlanguage deficits; most
patients eventually become mute
Average age of onset 60
“Reversible” Causes of Dementia
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?10% of all patients with dementia; in reality,
only 2-3% at most will truly have a reversible
cause of dementia
“Modifiable” Causes of Dementia
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Medications
Alcohol
Metabolic (b12, thyroid, hyponatremia,
hypercalcemia, hepatic and renal
dysfunction)
Depression? (likely marker though…)
CNS neoplasms, chronic subdural
NPH
Normal Pressure Hydrocephalus
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Triad:
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Gait disturbance
Urinary incontinence
Cognitive dysfunction
NPH
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Diagnosis: initially on neuroimaging
Miller Fisher test: objective gait assessment
before and after removal of 30 cc CSF
Radioisotope diffusion studies of CSF
Creutzfeldt-Jacob Disease
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Rapid onset and deterioration
Motor deficits
Seizures
Slowing and periodic complexes on EEG
Myotonic activity
Other infections and dementia
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Syphilis
HIV
MMSE
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24/30 suggestive of dementia (sens 87%,
spec 82%)
Not sensitive for MCI
Spuriously low in people with low educational
level, low SES, poor language skills,
illiteracy, impaired vision
Not sensitive in people with higher
educational background
Additional evaluation
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Clockface
Short assessments with good validity: 3 item recall
and clockface
Neurological exam (focality, frontal release signs
such as grasp, jawjerk; apraxia, cogwheeling, eye
movements)
Lab testing and neuroimaging
Apolipoprotein E epsilon 4 allele: probably not
Prognosis
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Previous estimate of median survival after
onset of dementia have ranged from 5-10
years
Length bias: failing to consider people with
rapidly progressive illness who died before
they could be included in the study
Prognosis…
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NEJM, april 2001
Data from Canadian Study of Health and
Aging, estimate adjusted for length bias, with
random sample of 10,263 people over age
65 screened for cognitive impairment; for
those with dementia, ascertained date of
onset and conducted followup for 5 years
Prognosis…
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821 subjects (396 with probably AD)
Unadjusted median survival 3.3 years
Median survival 3.1 years for those with
probable AD
Treatment of AD…
Tacrine
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Cholinesterase inhibitor
1 systematic review with 5 RCTs, 1434 people, 1-39
weeks
No difference in overall clinical improvement
Some clinically insignificant improvement in
cognition
Significant risk of LFT abnormalities: NO ON USE
Donepezil
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Aricept
Cholinesterse inhibitor
Easy titration (start 5/day, then 10)
Side effects: GI (nausea, diarrhea)
Associated with improved cognitive function;
main effect seems to be lessening of rate of
decline, delayed time to needing nursing
home/more intensive care
Other agents…
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Rivastigmine
Galantamine
Cholinesterase inhibitors
?more side effects, more titration required
Future directions:
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Prevention of delirium in at risk patients (cholinergic theory
of delirium)
Behavioral effects in those with severe dementia
Treatment of Lewy Body dementia
Treatment of mixed Vascular/AD dementia
Comments about cholinesterase
inhibitor studies…
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Highly selected patients (mild-mod dementia)
?QOL improvements…
Not known: severe dementia and mild CI
Memantine
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NEJM april 2003
Moderate to severe AD (MMSE 3-14)
N-methyl D aspartate (NMDA) receptor antagonist;
theory that overstimulation of NMDA receptor be
glutamate leads to progressive damage in
neurodegenerative diseases
28 week, double blinded, placebo controlled study;
126 in each group; 67% female, mean age 76, mean
MMSE 7.9
Memantine…
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Found less decline in ADL scores, less
decline in MMSE (-.5 instead of –1.2)
Problem: significant drop outs (overall 28%
dropout rate) in both groups; data analyzed
did not account for drop outs, followed those
“at risk”
Selegiline
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Unclear benefit
Less than 10mg day, selective MAO B
inhibitor
Small studies, not very conclusive
Vitamin E (alpha tocopherol)
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NEJM 1997: selegiline, vit E, both , placebo for tx of
AD
Double blind, placebo controlled, RCT with mod AD;
341 patients
Primary outcome: time to death, institutionalization,
loss of ADLS, severe dementia
Baseline MMSE higher in placebo group
No difference in outcomes; adjusted for MMSE
differences at baseline and found delay in time to NH
from 670 days with vit E to 440 days with placebo)
Ginkgo Biloba
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1 systematic review of 9 double blind RCTs
with AD, vascular, or mixed dementia
Heterogeneity, short durations
High withdrawal rates; best studies have
shown no sig change in clinician’s global
impression scores
Other treatments
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NO good evidence to support estrogens or
NSAIDS
Other treatments…
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Behavioural/agitation:
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Nonpharm strategies
Low dose newer antipsychotics (.5 risperidone, olanzepine);
Olanzepine has higher anticholinergic profile, but may
benefit/not worsen tremor/rigidity of Parkinson’s
Reasons for NH placement:
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Agitation
Incontinence
Falls
Caregiver stress
MMSE tips…
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No on serial sevens (months backwards, name
backwards… assessment of attention)
Assess literacy prior
Assess for dominant hand prior to handing paper
over
Do not over lead…
3 item repetition, repeat all 3 then have patients
repeat; 3 stage command, repeat all 3 parts of
command and then have patient do…