Cardiovascular contributions to dementia: Examining sex differences and female-specific factors

Abstract

Growing evidence underscores the importance of cardiovascular contributions to Alzheimer's disease and related dementias (AD/ADRD). While sex differences in cardiovascular disease (CVD) risk factors and outcomes are well established, the question of whether vascular contributions to AD/ADRD vary by sex has only recently garnered attention. In this narrative review, we discuss sex differences in conventional CVD risk factors (e.g., hypertension, dyslipidemia, diabetes), as well as underrecognized female-specific (e.g., menopause history, polycystic ovary syndrome, adverse pregnancy outcomes) and female-predominant (e.g., autoimmune conditions, breast cancer) CVD risk factors. Despite their relevance, these sex-specific considerations are rarely incorporated into current approaches to quantify CVD risk in AD/ADRD research. We offer recommendations to address these gaps and promote the use of sex-informed methods for studying cardiovascular contributions to AD/ADRD in women, which is essential for developing precision strategies to improve outcomes for all individuals at risk of dementia. HIGHLIGHTS: There are extensive sex differences in cardiovascular risk, dementia risk, and their interrelationships. Many cardiovascular risk factors confer greater risk for dementia in women than men. Existing approaches to quantifying cardiovascular risk often overlook sex differences and female-specific factors. Sex-informed approaches are essential for an accurate understanding of cardiovascular contributions to dementia.

Keywords: Alzheimer's disease; cardiovascular; dementia; sex differences; women's health.

FIGURE 1

Pathways between risk factors for cardiovascular disease (CVD), cardiovascular dysfunction/CVD, and Alzheimer's disease and related dementias (AD/ADRD) outcomes. The figure illustrates that sex differences and sex‐specific factors may influence the development of CVD risk factors, the manifestation of CVD, and progression to AD/ADRD, as well as the strength and direction of the associations among these conditions. Arrows represent possible direct and indirect pathways, with female (♀) and male (♂) symbols potential sex differences.

FIGURE 2

Key factors influencing cardiovascular and brain health across the female lifespan. This framework underscores the importance of sex‐informed study designs, data collection, and a life‐course approach to research on brain aging in women. It highlights the critical windows along the aging trajectory during which risk factors for Alzheimer's disease and related dementias may be most effectively identified, prevented, or modified to support optimal cognitive and brain health. PCOS, polycystic ovary syndrome; MHT, menopausal hormone therapy.