Understanding sex differences in dementia risk
Dementia is a global health priority, characterized by progressive memory loss and cognitive decline that disrupt daily living. While many studies report higher dementia incidence in women, especially in older ages, crude comparisons can be misleading. A key question is whether sex itself increases dementia risk once we account for other health factors that differ between men and women. A recent large prospective cohort from Israel provides important insights by examining how a broad array of medical conditions influences the apparent link between sex and incident dementia.
The study design at a glance
Researchers analyzed 53,224 adults born between 1922 and 1946 who were dementia-free at baseline. They were followed for up to 18 years (2002–2020), with dementia diagnosed via standardized clinical coding. Crucially, the analysis adjusted not only for demographics but also for 33 medical conditions grouped into ten medical domains, including psychiatric, cardiovascular, respiratory, and genitourinary diseases, among others. This comprehensive approach aimed to disentangle whether sex differences in dementia risk persist after accounting for health history.
Key findings: crude versus adjusted associations
In the unadjusted model, women showed a modestly higher risk of developing dementia than men (hazard ratio [HR] about 1.08). However, once background demographics and the full set of medical conditions were included, the association between sex and incident dementia largely disappeared (adjusted HR ≈ 1.02; not statistically significant). This shift suggests that the higher observed dementia rates in women in some studies may reflect differences in medical history rather than sex itself.
Which medical domains mattered most?
Complementary analyses shed light on how specific health domains influenced the sex-dementia link. Some domains, such as circulatory, respiratory, metabolic, digestive, and nervous system diseases, tended to strengthen the female association when adjusted for alone. By contrast, rheumatic and genitourinary diseases reduced the association toward null, and psychiatric disorders flipped the direction in some models, with men showing higher risk when psychiatric conditions were accounted for.
Notably, diseases of the circulatory system often yielded the largest effect sizes in women, aligning with broader evidence that cardiovascular health substantially shapes dementia risk. These findings underscore that sex differences in dementia risk are not solely biological but also reflect sex-specific patterns of comorbidity and late-life health trajectories.
Why these results matter for prevention and research
The study highlights a methodological point: failing to account for comorbidities can yield misleading conclusions about sex differences in dementia risk. For prevention science, this means that risk assessment and intervention strategies should consider an individual’s medical history in addition to sex. Interventions that improve cardiovascular and metabolic health, reduce inflammatory burden, and monitor urinary and rheumatic conditions may have differential effects across sexes and could help tailor prevention efforts.
Strengths, limitations, and future directions
The study’s strengths include a large, nationwide cohort with long follow-up, objective medical diagnoses, and a rigorous adjustment for a wide spectrum of conditions. Limitations include potential residual confounding from unmeasured factors such as education and lifestyle, and the absence of genetic data or dementia subtypes, which could reveal nuanced sex-specific patterns.
Future research should explore how sex hormones, genetics, and social determinants interact with comorbidity to shape dementia risk. Subtyping dementia (e.g., Alzheimer’s disease versus vascular dementia) could reveal distinct sex-specific pathways and inform targeted prevention.
Bottom line
When broad medical histories are considered, the sex difference in incident dementia risk largely attenuates. The pattern of association across specific disease domains suggests a nuanced landscape where sex interacts with health history to influence dementia risk. This advocates for sex-aware, condition-aware approaches in both research and clinical prevention strategies.
