Transcript Dementia: Diagnosis and Treatment

Dementia: Diagnosis and
Treatment
Dr Malekzadeh
Case
Mr. Jones is a 72-year-old gentleman brought to you by his
daughter for progressive memory loss. He denies any problems.
Previously an accountant, he is now unable to balance his check
book. He has had difficulty with getting lost while driving to the
store. He was diagnosed with depression two years ago after his
wife died. 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.
Question:
What is the definition of a dementia?
What is the “line” between “normal”
memory loss with age and dementia…
Cognitive Decline with Aging
Mild changes in memory and rate of
information processing
Not progressive
Does not interfere with daily function or
independence
DSM Criteria
1. Memory impairment
2. At least one of the following:
 Aphasia
 Apraxia
 Agnosia
 Disturbance in executive functioning
3. Disturbance in 1 and 2 interferes with daily
function or independence
4. Does not occur exclusively during delirium
Risk Factors for Dementia
Age
Family hx of AD or Parkinson’s (10-30%
risk of AD in patients with first degree
relative)
Head trauma
Depression (?early marker for dementia)
Low educational attainment?
?hyperlipidemia
?diabetes
HTN !!!
Question:
What are some classic features of an
Alzheimer’s type dementia?
Alzheimer’s Disease
60–80% of cases of dementia in older patients
Early personality changes
Loss of short term memory
Functional impairment
Visual spatial disturbances (early finding)
Apraxia
Language disturbances
Delusions/hallucinations (usually later in
course)
‫گروه‬
‫سالم‬
‫دمانس‬
‫ارجاع درون متنی‬
‫‪2‬‬
‫‪8‬‬
‫ارجاع برون متنی‬
‫‪1‬‬
‫‪9‬‬
‫حذف‬
‫‪2‬‬
‫‪4‬‬
‫جایگزینی‬
‫‪0‬‬
‫‪3‬‬
‫جمع‬
‫‪5‬‬
‫‪24‬‬
‫مقایسه خطاهای دستوری در گفتار افراد سالم و مبتال به دمانس‬
Alzheimer’s Disease
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 (especially for early types)
Normal/nonspecific EEG
MRI: bilateral hippocampal atrophy
(suggestive)
Question:
What features would make you think
more about a vascular etiology to a
dementia?
Vascular Dementia
Onset of cognitive deficits associated with a
stroke (but often no clear hx of CVA but
multiple small, undiagnosed CVAs)
Abrupt onset of sxs with stepwise deterioration
Findings on neurological examination
Infarcts on cerebral imaging (but ct/mri
findings often have no clear relationship)
Question:
What is the risk of dementia with
Parkinson’s disease?
Dementia with Parkinson’s
30% with PD may develop dementia;
Risk Factors:
Age over 70
 Depression
 Confusion/psychosis on levodopa
 Facial masking upon presentation
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Hallucinations and delusions

May be exacerbated by treatment
Dementia with Lewy Bodies
Cortical Lewy Bodies on path
10–20% of dementias
Compare to PD: Lewy Bodies in
substantia nigra
Overlap with AD and PD
40% patients with AD have LBs on path
Dementia with Lewy Bodies
Visual hallucinations (early)
Parkinsonism
Cognitive fluctuations
Dysautonomia
Sleep disorders
Neuroleptic sensitivity
Memory changes later in course
Dementia with Lewy Bodies
Visual hallucinations
2/3 of patients with DLB
 Rare in AD
 May precede other symptoms of DLB
 Psychosis, paranoia and other psychiatric
manifestations early in course

Dementia with Lewy Bodies
Parkinsonism
70–90%
 More bilateral and symmetric than with PD
 Tremor less common
 Bradykinesia, rigidity, gait changes

DLB: Neuroleptic Hypersensitivity
30–50% of patients
May induce Parkinsonian symptoms or
cognitive changes that are not reversible,
leading to rapid decline in overall status
NOT dose related
Slightly less likely with newer atypical
antipsychotics, but can STILL happen
DLB: Treatment
More progressive course than AD or
Vascular dementia
Possibly better response to cholinergic
drugs than AD or vascular dementias
?response of psychiatric type symptoms
to cholinergic agents/cholinesterase
inhibitors
Pick’s Disease
Subtype of frontal lobe dementia
Pick bodies (silver staining intracytoplasmic
inclusions in neocortex and hippocampus)
?Serotonergic deficit?
Language abnormalities and behavioral
disturbances
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Logorrhea (abundant unfocused speech)
Echolalia (spontaneous repetition of words/phrases)
Palilalia (compulsive repetition of phrases)
Fluent or non-fluent forms
“Modifiable” Causes of Dementia
Medications
Alcohol
Metabolic (b12, thyroid, hyponatremia,
hypercalcemia, hepatic and renal
dysfunction)
Depression? (likely marker though…)
CNS neoplasms, chronic subdural
NPH
Tacrine
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: NOT
USED
Donepezil
Aricept
Cholinesterse inhibitor
Easy titration (start 5/day, then 10)
Side effects: GI (nausea, diarrhea)
Can be associated with bradycardia
Main effect seems to be lessening of rate
of decline, delayed time to needing
nursing home/more intensive care
Other Agents
Rivastigmine
Galantamine
Cholinesterase inhibitors
?more side effects, more titration required
Comments about Cholinesterase
Inhibitor Studies
Highly selected patients (mild – moderate
dementia)
?QOL improvements
Not known: severe dementia and mild CI
Memantine
NEJM April 2003
Moderate to severe AD (MMSE 3–14)
N-methyl D aspartate (NMDA) receptor
antagonist; theory that overstimulation of
NMDA receptor by glutamate leads to
progressive neurodegenerative damage
28-week, double blinded, placebo controlled
study; 126 in each group; 67% female, mean
age 76, mean MMSE 7.9
Selegiline
Unclear benefit
Less than 10mg day, selective MAO B
inhibitor
Small studies, not very conclusive
Vitamin E (Alpha Tocopherol)
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 Primary 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
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 significant change in clinician’s
global impression scores
Other Treatments
NO good evidence to support estrogens
or NSAIDS
Other Treatments
Behavioral/agitation:
Nonpharmacologic strategies
 Reasons for NH placement:

Agitation
 Incontinence
 Falls
 Caregiver stress

?Antipsychotics
NO data to support any significant
benefit for treating behavioral symptoms
of dementia with antipsychotic agents
Small group of patients with active
psychoses, disturbing hallucinations, or
aggressive behaviors who may have some
benefit
Antipsychotics
Side Effects:
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Sedation
Anticholinergic effects
Prolonged QT
Edema
Orthostasis
Weight gain
Confusion
Warnings:
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FDA black box warning for increased mortality (OR
1.5–1.7), and increased ?increased stroke risk
Antipsychotics
NO if you suspect
DLB
Antipsychotics
Risperidone (0.5 BID)
Olanzepine (zyprexa): 2.5–5 mg/day
Quetiapine (seroquel)
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Rapid titration, use in PD
12.5–200 mg/day
Clozapine
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Use in PD (least risk of tremor)
Agranulocytosis and limited use
Ziprasidone (geodon)
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QT prolongation