Sex Differences in Alzheimer Disease-Related Biomarkers and Dementia Risk

Alzheimer disease (AD) and related dementias represent intricate, multifaceted neurodegenerative conditions, with AD prevailing as the most common form. The escalating incidence and prevalence observed across global populations could be attributed to a deficiency in primary and/or secondary prevention strategies. Despite affecting both sexes, AD exhibits a higher prevalence among females. While the extended life expectancy of women might contribute to this discrepancy, studies have revealed sex disparities in incidence, progression, pathology, and risk profiles for AD; the underlying mechanisms of which largely remain unclear.

Comprehensively grasping sex differences in dementia risk is imperative. Although these risk factors present a diverse and intricate landscape, discerning the impact of sex and gender influences on AD risk could foster the development of precise, tailored treatment and prevention approaches. Reported sex differences in risk profiles often exhibit varying magnitudes and inconsistencies across studies, potentially stemming from divergent study designs, heterogeneous definitions, disparate data collection methodologies for risk factors, and the impact of residual confounding.

Simultaneously, encouraging outcomes from interventional studies on modifying risk factors for cognitive health underscore the necessity of targeting specific subgroups and crafting ‘personalized’ interventions, considering the documented sex and gender disparities. Clarifying sex differences and their implications in the relationship between established and unidentified risk factors and dementia risk or prevalence, as well as diagnostic and predictive biomarkers of the neurodegenerative process, will prove pivotal for devising personalized interventions.

Enhancing our comprehension of sex-based variances in dementia risk holds potential for advancing care and treatment for individuals of all genders. This understanding stands to bolster endeavors in both dementia prevention and treatment. In this chapter, we summarize existing evidence concerning sex-related disparities in AD, as well as risk factors and biomarkers associated with dementia and cognitive decline, providing insights and perspectives around their ramifications for dementia prevention. Furthermore, we offer recommendations for integrating sex-specific strategies into the realm of dementia prevention research and healthcare applications, including from a global health standpoint.