Description

• Alzheimer disease (AD) is the most common cause of dementia: 60–80% are 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
• 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.
• The U.S. Preventive Services Task Force has a grade I (insufficient evidence) recommendation on asymptomatic routine screening for dementia, although cognitive assessment is required for Medicare Initial and Annual Wellness Visits.
• Advanced care planning is Medicare reimbursable

Epidemiology

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

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: 11 new cases per 1,000 people
• ≥85: 37 new cases per 1,000 people

>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.

• 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:
  • Age
  • Gender (due to longer lifespan in women)
  • Family history
  • Genetic mutations
  • APOE-e4 gene variant: e4 heterozygous 2- to 3-fold risk; homozygous 8-fold risk (vs. e2 or e3)
• Cardiovascular disease–related risk factors:
  • 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:
  • 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.
• NSAIDs, estrogen, and vitamin E do not delay AD onset; insufficient evidence for statins and proton pump inhibitors
• Healthy lifestyle (e.g., exercise, sleep), potentially modifiable risk factors, may prevent or delay AD at the individual and population health level.
• 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