DEMENTIA
Michael J. Mintzer, MD
Associate Professor of Medicine
University of Miami School of Medicine
Director of Community Academic Partnerships
Miami VAMC and GRECC
Dementia
Learning Objectives:
• Define dementia
• Describe the common dementias in the
elderly
• Differentiate the issues of reversibility,
comorbidity, and arrestability
• Describe the current dilemmas in the
pharmacological treatment of dementia
Dementia
Definition
A: The development of multiple cognitive deficits manifested by both:
(1) Memory impairment (impaired ability to learn new information
or to recall previously learned information)
(2) One or more cognitive disturbances:
(a) aphasia (language disturbance)
(b) apraxia (impaired ability to carry out motor
activities despite intact motor function)
(c) agnosia (failure to identify objects despite intact
sensory function)
(d) disturbance in executive functioning (planning,
organizing, sequencing, abstracting, etc.)
Dementia
Definition
B: The cognitive deficits in Criteria A1 and A2 each cause significant
impairment in social or occupational functioning and represent a
significant decline from previous level of functioning
C: Features specific to the clinical presentation of (1) Alzheimer's
Disease, or (2) vascular disease, or (3) other general medical
condition, or (4) the persisting effects of a substance, or (5)
multiple etiologies or (6) "not otherwise specified.“
D,E,F: The cognitive deficits in Criteria A1 and A2 are not due to a
different specific illness (i.e., a different form of dementia, delirium
or psychiatric illness).
Dementia
Etiologies
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Degenerative (Alzheimer’s, Lewy body, Parkinson’s)
Vascular (MID, large stroke, vasculitis, Binswanger’s)
Metabolic (hypothyroid, B12 deficiency)
Infectious (AIDS, Syphilis, late post TB)
Hypoxic (s/p CPR, s/p anesthesia?, s/p RT?)
Toxic (heavy metal)
Intracranial lesion (mass)
Trauma (dementia pugilistica)
Dementia
Most Common Causes of Dementia in the
Elderly
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Alzheimer’s disease (AD)(50-60%)*
Diffuse Lewy body disease (DLBD)(15-20%)
Vascular dementia (VD)(15-20%)
Parkinson’s dementia (1-3%)
Frontotemporal dementia (1-2%)
All other
*In
the past, DLBD was included in this category. In addition, up to 10% of
dementias are mixed AD plus VD
Dementia
Reversible or not!
• The definition does NOT define permanence of the
lesion (pseudodementia?)
• Data suggests there are very few reversible dementias
in the elderly (depression, chronic intoxication by
medication, hypothyroidism) (Larson)
• Co-morbid conditions account for most of the
reversibility in dementia in the elderly (Larson)
• “Arrestable” or “Remediable” may be better terms
(Maletta)
Dementia
Minimum Cognitive Impairment (MCI)
• Definition
• What do we do with it?
Dementia
Clinically helpful EARLY clues
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Alzheimer’s
Diffuse LBD
Vascular
FT / Pick’s
Parkinson’s
Memory
Attention, Exec Func, Visio-spatial
Focal signs, temporal relationship
Behavioral, social skills, hygiene
Dementia does NOT occur early in
Parkinson’s disease
Dementia
Alzheimer’s disease
• Deposition of beta-amyloid in senile
plaques diffusely in the brain, often
around blood vessels
• Neurofibrillary tangles
• Loss of neurons
• Brain shrinkage especially cortex
Alzheimer’s Risk Factors
1. Age
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Prevalence doubles every 5 years after age 60
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Fourfold increase risk overall. The presence of the
ApoE4 allele increases risk but is not predictive.
2. Family History
3. Gender
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Woman probably more than men
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Repeated, especially in men
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Characteristic brain pathology by age 40
4. Head Trauma
5. Down’s Syndrome
6. Educational Level / Mental Activity
Risk Factors
(continued)
7. Estrogen plus progesterone
• Doubles risk of dementia
8.
9.
10.
11.
Environment ?
Hypertension ?
Elevated Cholesterol ?
Depression ?
Dementia
Medications for Alzheimer’s disease
• Acetylcholinesterase inhibitors: indicated for mild to
moderate dementia. Increases acetylcholine in
synapses
• Memantine (Namenda): indicated for moderate to
severe dementia and used with ACI. Selective blocks
the excitotoxic effects of glutamate while allowing the
physiologic transmission for normal cell function
Acetylcholinesterase inhibitors
Do they work when they work?
• Using family – fewer problem behaviors
• Using NH placement – save ~2 yrs
• Using metrics (MMSE) - minimal
incremental improvement
Memantine
• Works for moderate to severe
• Works alone
• Works with ACI
Alzheimer’s Disease
What else works?
• Vitamin E
• Statins?
Factors Contributing to [Aßs]
24S-OH cholesterol
cerebrocholesterol
cholesterol
ApoE4
Aging
[Aßs]
LRP
CNS growth/repair
inflammation
APP
Adapted from Hazzard 2004 AGS annual meeting
Cholesterol & Alzheimer’s
• In human studies there are more ß-amyloid
plaques in patients dying from heart disease than
from other causes (Sparks 1991)
• Cholesterol >240 between age 40-50 predicted
higher AD risk 30 years later (Notkolo 1998)
• In animal studies, rabbits fed high cholesterol diet
led to plaques that regressed when cholesterol was
removed
What do we do with our effective cholesterol
lowering drugs?
Adapted from Hazzard 2004 AGS annual meeting
Cholesterol & Alzheimer’s
• It’s too early to recommend adding
“statins” for the treatment of Alzheimer’s
• We need well controlled studies across
the spectrum of dementia
Adapted from Hazzard 2004 AGS annual meeting
Let’s Add to the Confusion
• ACI and memantine(?) might work for
vascular dementia, too ! ! !
Summary
• Dementia is easy to diagnose
• There are features that help differentiate the
common dementias in the elderly
• Reversible dementias are uncommon in the
elderly but many dementias are arrestable
• Treating comorbid conditions allows those
with dementia to function at their best
• Current drugs used for Alzheimer’s may help
vascular dementia as well
• Vitamin E is worth a try but not statins