Alzheimer Disease

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Basics

Description

  • Alzheimer disease (AD) is the most common cause of dementia: 60–80% of those afflicted with dementia.
  • AD is a progressive, irreversible, degenerative neurologic disease that results in neuron death.
  • AD is the sixth leading cause of death in the United States (1).
  • People ≥65 years with new AD live 4 to 8 years on average.
  • AD is underdiagnosed (~50%), and many people diagnosed with AD are unaware of diagnosis (>50%).
  • Economic burden in 2018: >$277 billion, projected at $1.1 trillion by 2050 (1)
  • Dementia should be distinguished from:
    • Age-related cognitive decline: lifelong process of changes in mental ability and memory; highly variable and part of normal aging
    • Mild cognitive impairment (MCI): greater impairment than cognitive decline with individual and/or friends—family able to note impairment
      • MCI: People are generally able to live independently from a cognitive perspective.
      • MCI: affects 15–20% of those ≥65 years, with 32–38% developing dementia within 5 years
  • AD diagnostic classification:
    • Preclinical AD: research settings only at this time; no cognitive symptoms, AD biomarkers present
    • MCI due to AD: if AD biomarkers present and not attributed to other causes; impairment often only in memory; no major social/occupational deficits
    • Dementia due to AD:
      • Early stage: memory impairment beyond MCI
      • Middle stage: impairment in communication and response to environment
      • Late stage: lose ability to appropriately recognize and respond to environment
  • System affected: nervous
  • Synonym(s): presenile dementia; senile dementia of the Alzheimer type
Geriatric Considerations
  • “Welcome to Medicare” preventive visit (first 12 months of enrollment) and Medicare Annual Wellness Visit both require assessment of cognitive function.
  • Even though the U.S. Preventive Services Task Force has a grade I (insufficient evidence) recommendation on asymptomatic routine screening for dementia
  • Advanced care planning: Medicare reimbursable

Epidemiology

  • Predominant age: >65 years
  • Incidence: females = males
  • Prevalence: females > males, due to longer average lifespan in women

Incidence

New cases of AD in the United States: 484,000/year (1)

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

>5.7 million in United States; ~44 million worldwide

  • 14.4 million in United States by 2050
  • 1 in 10 of those ≥65 years have AD dementia.
  • 32% of those ≥85 years have AD dementia.
  • ~200,000 in United States with early-onset AD (<65 years)

Etiology and Pathophysiology

  • Progressive, irreversible disease where cognitive impairment worsens over time
  • Caused by β-amyloid plaques outside of neurons and τ protein tangles inside of neurons, resulting in loss of connections between neurons and cell death
  • Age, genetics, systemic disease, lifestyle behaviors, and other factors may influence AD progression.

Genetics
  • Autosomal dominant: <5% of AD, usually early onset (<65 years)
  • Familial inheritance AD (nonautosomal dominant): 15–25% of AD, may be early- or late-age onset
  • Sporadic, idiopathic: most 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; homozygous 10-fold risk (vs. e2 or e3)
  • Cardiovascular disease–related risk factors (1,2):
    • Hypertension (HTN) (especially in midlife years)
    • Obesity
    • Diabetes and impaired glucose processing
    • Hyperlipidemia
    • Tobacco use
    • Unhealthy diet
    • Lack of physical activity/exercise
    • Cerebrovascular (stroke) risks and injury
  • Other potentially modifiable risk factors (1,2):
    • Less 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
    • Possible environmental factors (e.g., pollution)

General Prevention

  • Slowing/preventing cognitive decline, MCI, and AD are the top interest and concern of Americans ≥50 years.
  • Evidence suggests that HTN management, increased physical activity, cognitive training may delay/prevent cognitive decline, MCI, and AD (2)[B].
  • NSAIDs, estrogen, and vitamin E do NOT delay AD onset; insufficient evidence for statins (2)[A]
  • Healthy lifestyle (e.g., exercise, sleep), potentially modifiable risk factors, may prevent or delay AD at the individual and population health level (2)[B].
  • Actions to avert delirium during hospitalizations
  • Treat psychiatric conditions (e.g., depression).
  • Numerous medication can cause decreased cognition and delirium in the elderly.

Commonly Associated Conditions

  • Down syndrome
  • Depression

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