Description

A decline in cognitive function, which includes memory deficits and/either of: Apraxia, agnosia, aphasia, or disturbance in executive functioning:

• Alzheimer dementia (AD):
  • Progressive cognitive decline. Most common above age 65
• Vascular dementia (VaD):
  • Usually correlated with a cerebrovascular event and/or cerebrovascular disease
  • Stepwise deterioration with periods of clinical plateaus
• Lewy body dementia:
  • Fluctuating cognition associated with parkinsonism, hallucinations and delusions, gait difficulties, and falls
• Frontotemporal dementia:
  • Language difficulties, personality changes, and behavioral disturbances
• Creutzfeldt-Jacob disease (CJD):
  • Very rare; rapid onset
• HIV dementia

Epidemiology

• In patients age ≥71 years:
  • AD: 70%
  • VaD: 17%
  • Other: 13%
• Estimated 5.4 million Americans had AD in 2010:
  • 5 million >65 years of age; 200,000 <65 years

Risk Factors

• Age
• Female > Male
• Genetic predisposition
• Hypertension: AD; VaD
• Hypercholesterolemia: AD; VaD
• Diabetes: VaD
• Cigarette smoking: VaD
• Endocrine abnormalities: Hypothyroidism, Cushing syndrome
• Metabolic abnormalities: thiamine and vitamin B₁₂ deficiency
• Chronic alcoholism, other drugs
• Lower educational status
• Head injury early in life
• Sedentary lifestyle

• AD: Positive family history in 50%, but 90% AD is sporadic:
  • APOE4 increases risk, but full role unclear
• Familial/Autosomal-dominant AD accounts for <5% AD:
  • Amyloid precursor protein (APP), presenilin-1 (PSEN-1), and presenilin-2 (PSEN-2)

General Prevention

• Treat reversible causes of dementia, such as drug induced, alcohol induced, and vitamin deficiencies.
• Treat hypertension, hypercholesterolemia, and diabetes.
• No evidence for statins (or any other specific medication) to prevent onset of dementia (1)[A]

Etiology

• AD: Unknown, but involves β-amyloid protein accumulation and/or neurofibrillary tangles (NFTs), synaptic dysfunction, neurodegeneration, and eventual neuronal loss:
  • Age, genetics, systemic disease, behaviors (smoking), and other host factors may influence the response to amyloid-β and/or the pace of progression toward the clinical manifestations of AD.
• VaD:
  • Cerebral atherosclerosis/emboli with clinical/subclinical infarcts

Commonly Associated Conditions

• Anxiety and depression
• Psychosis (delusions; delusions of persecution are common)
• Delirium
• Behavioral disturbances (agitation, aggression)
• Sleep disturbances