Sex and gender differences in genetic and lifestyle risk and protective factors for dementia

Abstract Approximately two-thirds of individuals diagnosed with Alzheimer’s disease are women. Although women tend to have longer life expectancy than men, this does not entirely explain the differences in the prevalence of dementia and Alzheimer’s disease. Some evidence suggests that men and women have different patterns of risk and protective factors across the lifespan. The goal of this chapter is to summarize the current evidence on sex differences in genetic and modifiable lifestyle factors that are associated with dementia risk. These include demographic factors such education, vascular, metabolic, lifestyle, and psychosocial factors, and sex-specific factors such as menopause and andropause. Potential mechanisms such as neural reserve and resilience are also summarized. The chapter also summarizes the evidence from recent multidomain lifestyle intervention trials, and the intervention response observed in men and women. While there have been insightful advancements in the field, many important questions still remain. Considerations for future research and risk reduction initiatives are also highlighted.