DEMENTIA

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DEMENTIA
Michael J. Mintzer, MD Associate Professor of
Medicine University of Miami School of
Medicine Director of Community Academic
Partnerships Miami VAMC and GRECC
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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

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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.)

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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).

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Dementia

• Etiologies
• Degenerative (Alzheimers, Lewy body,
  Parkinsons)
• Vascular (MID, large stroke, vasculitis,
  Binswangers)
• 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)

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Dementia

• Most Common Causes of Dementia in the Elderly
• Alzheimers disease (AD)(50-60)
• Diffuse Lewy body disease (DLBD)(15-20)
• Vascular dementia (VD)(15-20)
• Parkinsons 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
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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)

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Dementia

• Minimum Cognitive Impairment (MCI)
• Definition
• What do we do with it?

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Dementia

• Clinically helpful EARLY clues
• Alzheimers Memory
• Diffuse LBD Attention, Exec Func, Visio-spatial
• Vascular Focal signs, temporal relationship
• FT / Picks Behavioral, social skills, hygiene
• Parkinsons Dementia does NOT occur early in
• Parkinsons disease

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Dementia

• Alzheimers 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

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Alzheimers Risk Factors

• Age
• Prevalence doubles every 5 years after age 60
• Family History
• Fourfold increase risk overall. The presence of
  the ApoE4 allele increases risk but is not
  predictive.
• Gender
• Woman probably more than men
• Head Trauma
• Repeated, especially in men
• Downs Syndrome
• Characteristic brain pathology by age 40
• Educational Level / Mental Activity

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Risk Factors (continued)

• Estrogen plus progesterone
• Doubles risk of dementia
• Environment ?
• Hypertension ?
• Elevated Cholesterol ?
• Depression ?

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Dementia

• Medications for Alzheimers 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

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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

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Memantine

• Works for moderate to severe
• Works alone
• Works with ACI

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Alzheimers Disease

• What else works?
• Vitamin E
• Statins?

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Factors Contributing to Aßs
Aßs
24S-OH cholesterol cerebrocholesterol
cholesterol
ApoE4
Aging
inflammation
LRP
APP
CNS growth/repair
Adapted from Hazzard 2004 AGS annual meeting
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Cholesterol Alzheimers

• In human studies there are more ß-amyloid plaques
  in patients dying from heart disease than from
  other causes (Sparks 1991)
• Cholesterol gt240 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
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Cholesterol Alzheimers

• Its too early to recommend adding statins for
  the treatment of Alzheimers
• We need well controlled studies across the
  spectrum of dementia

Adapted from Hazzard 2004 AGS annual meeting
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Lets Add to the Confusion

• ACI and memantine(?) might work for vascular
  dementia, too ! ! !

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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 Alzheimers may help
  vascular dementia as well
• Vitamin E is worth a try but not statins