Alzheimers: Reason to Hope

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AlzheimersReason to Hope?
Ola A. Selnes Professor, Division of Cognitive
Neuroscience Neurology, Johns Hopkins Univ.
School of Medicine
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Dementia
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DEMENTIA

• Progressive decline in cognitive functions
• Of sufficient severity to interfere with
  occupational or social functioning
• Gradual onset and slow progressive decline

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What is the difference between dementia and
Alzheimers disease?
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Dementia umbrella term for several diseases

• Alzheimers Disease
• Picks Disease
• Creutzfeldt-Jacob Disease
• Fronto-temporal Dementia
• Primary Progressive Aphasia
• Cortico-Basal Degeneration
• Progressive Supranuclear Palsy
• Vascular Dementia

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DEMENTIA Classification by brain involvement

• CORTICAL DEMENTIAS
• Involves gray matter of the brain
• Alzheimers disease
• Picks disease
• Creutzfeldt-Jacob Disease
• SUB-CORTICAL DEMENTIAS
• Involves subcortical white matter
• Vascular dementia
• Normal Pressure Hydrocephalus

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Classification by age of onset

• Early onset (before age 65)
• Familial Alzheimers Disease
• Mutations on chromosomes 1, 14 and 21
• Fronto-temporal dementia
• Tau-protein abnormalities
• Late onset
• Sporadic onset Alzheimers Disease
• Lewy Body Dementia
• Vascular Dementia
• Hippocampal Sclerosis

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Alzheimers Pathology

• Neurofibrillary tangles
• Amyloid Plaques
• Unique markers of the disease
• Direct cause of the clinical expression of the
  disease?

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A change in our thinking about the Clinical
expression of Alzheimers Disease?

• The Nun-study
• Community based neuropathological studies

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The Nun study
Photo Time Magazine

• Snowdon DA, Greiner LH, Mortimer JA, Riley KP,
  Greiner PA, Markesbery WR
• Brain infarction and the clinical expression of
  Alzheimer disease The Nun Study
• JAMA, 277(10)813-817, 1997.  

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The Nun Study

• 102 college educated women aged 76 100 years
• Evaluated with cognitive tests
• Agreed to brain autopsy
• Cerebrovascular disease (large and small strokes)
  as important for whether the person developed
  dementia as the degree of Alzheimers pathology

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Neuropathological investigations of patients with
Alzheimers Dementia

• Up until a decade ago, limited to patients with
• early onset disease
• atypical features
• family history of AD
• So whats wrong with that?

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Neuropathological investigations of
Community-Dwelling individuals

• Indeed, in older persons without dementia, AD
  i.e. plaques tangles was the most common
  pathology, followed by infarctions.
• Mixed pathologies, most commonly AD and
  infarctions, are the most common diagnoses in
  those with a clinical diagnosis of dementia.
• Schneider JA et al. Neurology, 2007

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Take home message

• The presence of vascular disease increases the
  likelihood of the clinical expression of dementia
• If we can reduce the degree of cerebrovascular
  disease in old age, perhaps we reduce the
  incidence of dementia?

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How common is cerebrovascular disease?

• Annual incidence of first-ever clinical stroke in
  US
• 783,000
• Williams GR BMC Neurology 2001
• Annual incidence of MRI defined silent infarct
• 11 million
• Leary MC Cerebrovasc Dis. 16280-5, 2003

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Silent Brain Infarcts by Age Rotterdam Study

• N 1,077
• 60 - 90 years
• N 217 (20) w/ clinically asymptomatic infarcts
• female gt male prev.
• age
• hypertension

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How to reduce the risk of late-life
cerebrovascular disease?

• Blood pressure control
• Blood glucose control
• Cholesterol control
• Regular exercise (cardio)
• Diet
• Quit smoking
• Have a glass of wine or two each day

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Epidemiological studies linking dementia and
midlife risk factors

• Whitmer RA et al.
• Cohort of 8,845 HMO participants
• The presence of multiple cardiovascular risk
  factors at midlife substantially increases risk
  of late-life dementia in a dose-dependent manner.
• NEUROLOGY 64277-281, 2005

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Mid-life obesity and risk of dementia

• 3-fold increase in risk of dementia in those with
  the highest abdominal diameter
• 50 of adults have central obesity

iStockphoto/Simone van den Berg
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• Alzheimers dementia is still an incurable
  disease the disease always prevails
• Recent data suggests that cerebrovascular disease
  increases the likelihood of the clinical
  expression of AD
• Therefore, a reduction in cerebrovascular disease
  may substantially decrease the number of patients
  with late-life dementia

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• A daily walk or other cardiovascular exercise may
  ultimately be more protective against cognitive
  loss or decline than cross-word puzzles