Alzheimer Disease



  • Alzheimer disease (AD) is a progressive, irreversible, degenerative neurologic disease that results in neuron death.
  • AD represents 60–80% of dementia.
  • AD is the sixth leading cause of death in the United States.
  • People aged ≥65 years with new AD live 4 to 8 years on average.
  • AD is underdiagnosed (~50%), and >50% with AD unaware of diagnosis
  • Economic burden in 2023: ~$245 billion, projected $1.1 trillion by 2050 (1)
  • Dementia should be distinguished from:
    • Age-related cognitive decline: lifelong changes in mental ability and memory; part of normal aging
    • Mild cognitive impairment (MCI): greater impairment than cognitive decline
      • MCI: People are generally able to live independently from a cognitive perspective.
      • MCI: affects 17–22% of those aged ≥65 years, with 32–38% developing dementia ≤5 years (1)
  • AD diagnostic classification:
    • Preclinical AD: no cognitive symptoms, AD biomarkers present
    • MCI due to AD: very mild impairment
    • Dementia due to AD:
      • Mild: impairment in some activities
      • Moderate: impairment in many activities
      • Severe: impairment in most activities
  • System(s) affected: nervous
  • Synonym(s): presenile dementia; senile dementia of the Alzheimer type


  • Predominant age: >65 years
  • Incidence: females = males
  • Prevalence: females > males

New cases of AD in the United States: 484,000/year

  • 65 to 75 years: 2 new cases per 1,000 people
  • 75 to 84 years: 11 new cases per 1,000 people
  • ≥85 years: 37 new cases per 1,000 people

~6.7 million in the United States; ~50 million worldwide (1)

  • 13.8 million in the United States by 2050
  • 1 in 9 of those aged ≥65 years have AD dementia.
  • 33.3% of those aged ≥85 years have AD dementia.
  • ~200,000 in United States with early-onset AD (age <65 years)

Etiology and Pathophysiology

  • Progressive, irreversible disease, worsening cognitive impairment
  • β-Amyloid plaques outside of neurons and τ protein tangles inside of neurons, resulting in loss of connections and neuron death.
  • Age, genetics, systemic diseases, and lifestyle behaviors may influence AD progression.


  • Autosomal dominant: <5% of AD, usually early onset (age <65 years)
  • Familial inheritance AD (nonautosomal dominant): 15–25% of AD

Risk Factors

  • Nonmodifiable risk factors: (1),(2),(3)
    • Age, gender (due to longer lifespan in women)
    • Family history, genetic mutations
    • APOE-e4 gene variant: e4 heterozygous 2- to 3-fold risk; e4 homozygous 8-fold risk
    • Racial and ethnic differences in AD exist.
  • Cardiovascular disease–related risk factors:
    • Hypertension (HTN) (especially in midlife years); hyperlipidemia
    • Obesity, diabetes, and impaired glucose processing
    • Tobacco use, unhealthy diet, lack of physical activity
    • Cerebrovascular (stroke) risks and injury
  • Other potentially modifiable risk factors:
    • Fewer years of formal education (<8th grade)
    • Lack of continuous brain activity—learning
    • Traumatic brain injuries: repetitive mild and moderate/severe
    • Lack of social engagement
    • Late-life depression
    • Poor quality and inadequate sleep
    • Hearing and vision deficits
    • High alcohol consumption
    • Environmental factors (e.g., air pollution)

General Prevention

  • Cognitive decline and impairment are top concerns of people aged >50 years.
  • HTN management, increased physical activity, and cognitive training may delay/prevent cognitive decline, MCI, and AD (3)[B].
  • NSAIDs, estrogen, and vitamin E do not delay AD onset; insufficient evidence for statins and proton pump inhibitors (3)[B]
  • Healthy lifestyles may prevent or delay AD (3)[B].
  • Treat psychiatric conditions and avert delirium during hospitalizations.

Commonly Associated Conditions

  • Down syndrome
  • Depression

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