Description

• 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

Epidemiology

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

Incidence
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

Prevalence
~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.

Genetics

• 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