Alzheimer Disease

Alzheimer Disease is a topic covered in the Washington Manual of Medical Therapeutics.

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General Principles

Alzheimer disease (AD) is the most common neurodegenerative disorder in older individuals (>60 years old), typically characterized by memory problems and inability to independently perform activities of daily living.

Epidemiology

  • Prevalence is <1% before age 65, 5%–10% at age 65, and approximately 45% by age 85. Approximately 5.7 million Americans have AD.
  • Inherited forms of AD manifest typically before age 65 years and are associated with mutations in amyloid precursor protein (APP) gene on chromosome 21, presenilin-1 gene on chromosome 14, and presenilin-2 gene on chromosome 1.
  • The greatest risk factor for late-onset/sporadic AD is the presence of the apolipoprotein ε4 variant.
  • Lifetime risk doubles if a sibling or parent is diagnosed with AD.
  • It is common for AD patients to present at late stages of the disease after an unrelated medical illness unmasks signs and symptoms of the disease that had previously gone unrecognized by the family.
  • Pseudodementia (cognitive impairment related to comorbid depression) should be considered in the appropriate clinical context.

Pathophysiology

Pathologic diagnosis requires presence of both neurofibrillary tangles because of tau and neuritic plaques composed of amyloid.

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General Principles

Alzheimer disease (AD) is the most common neurodegenerative disorder in older individuals (>60 years old), typically characterized by memory problems and inability to independently perform activities of daily living.

Epidemiology

  • Prevalence is <1% before age 65, 5%–10% at age 65, and approximately 45% by age 85. Approximately 5.7 million Americans have AD.
  • Inherited forms of AD manifest typically before age 65 years and are associated with mutations in amyloid precursor protein (APP) gene on chromosome 21, presenilin-1 gene on chromosome 14, and presenilin-2 gene on chromosome 1.
  • The greatest risk factor for late-onset/sporadic AD is the presence of the apolipoprotein ε4 variant.
  • Lifetime risk doubles if a sibling or parent is diagnosed with AD.
  • It is common for AD patients to present at late stages of the disease after an unrelated medical illness unmasks signs and symptoms of the disease that had previously gone unrecognized by the family.
  • Pseudodementia (cognitive impairment related to comorbid depression) should be considered in the appropriate clinical context.

Pathophysiology

Pathologic diagnosis requires presence of both neurofibrillary tangles because of tau and neuritic plaques composed of amyloid.

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