Women and Alzheimer's disease

ABSTRACT

Approximately, two-thirds of individuals with Alzheimer's disease (AD) are women. Though previously attributed to differences in lifespan, accumulating evidence suggests that the reasons for the higher prevalence of AD in women are multifactorial and related to differences in risk factors, biomarkers, and neuropathology. Sex also contributes to significant disease heterogeneity, which has important implications for prevention and treatment. This chapter discusses the evidence for sex differences in AD, with an emphasis on disease presentation, biomarkers, pathophysiology, progression, and risk. Women tend to present later in the disease course and with different clinical features, progress faster, and are disproportionately affected by the APOE-ϵ4 risk allele and AD neuropathologic changes. Lifetime estrogen exposure, pregnancy, and menopause also affect a woman's risk for cognitive decline later in life. Despite such differences, women are dramatically underrepresented in pharmacologic randomized control trials, leading to significant gaps in knowledge regarding the most effect AD treatment strategies for women. Both researchers and providers need to be aware of sex differences in AD risk, presentation, and outcomes to develop sex-specific prevention and treatment strategies, as well as provide optimum healthcare to women as they age. © 2023 Elsevier Inc. All rights reserved.