Chapter 21: The Neuropsychiatry of Alzheimer’s Disease

EPIDEMIOLOGY

Prevalence/Incidence

More than 5.7 million Americans are currently living with Alzheimer’s disease (AD) dementia, a condition that affects 1 in 10 U.S. adults over the age of 65.¹ AD is the primary etiology for the majority of dementia cases, accounting for 60–80% of dementia cases worldwide.¹ The prevalence of AD dementia increases with age, from 3% of people age 65–74, to 17% of people age 75–84, to 32% of people age 85 years and older.² As the U.S. population ages, the number of Americans with AD dementia is projected to expand more than twofold to 13.8 million by 2050 (Figure 21-1).² It is now recognized that AD begins with a long silent interval prior to the onset of symptoms. Therefore, current prevalence data for AD underestimate the true number of Americans affected across the disease spectrum—individuals who are impaired as well as those with presymptomatic disease who are at high risk of progression to impairment.^3–5

Risk Factors

The strongest known risk factors for sporadic or late-onset AD are older age,⁶ family history of dementia,⁷ and the apolipoprotein E ε4 (APOE4) allele.⁸ Clinically diagnosed probable AD dementia is more common in women compared to men, with women accounting for nearly two-thirds of affected individuals.² This gender discrepancy is commonly attributed to women having a longer life expectancy than men,⁹ however, other sex-specific factors have been reported.^10–13 AD prevalence rates also differ across racial and ethnic groups. Compared to Caucasian Americans, Hispanics are one and one-half times more likely to develop AD dementia.¹⁴ African Americans are twice as likely to have AD dementia than older white Americans.^14–16 Lower educational attainment and socioeconomic status are independent risk factors for AD that contribute to differences in AD risk by race.^17–20 Significant traumatic brain injury has been associated in some studies with increased risk of developing AD dementia later in life.^21,22 Accumulating evidence suggests that neuropsychiatric symptoms, such as depression, anxiety, and apathy, may be initial manifestations of neurodegenerative brain changes and, when present, these symptoms increase both the risk and rate of progression to dementia.²³ Risk of cognitive impairment due to AD may be mitigated by lifestyle factors, particularly when addressed or implemented in young adulthood or middle age. Regular physical exercise,²⁴ a healthy diet,²⁵ management of cardiovascular risk factors including hypertension, dyslipidemia, and diabetes mellitus,²⁶ and lifelong social²⁷ and cognitive engagement^28,29 may be protective factors ...