Overview
Dementia is a leading cause of disability and mortality worldwide. While many studies report higher dementia incidence in women, recent evidence suggests that sex differences may largely reflect the prevalence of underlying medical conditions rather than biology alone. A large, 18-year prospective study from Israel examined whether accounting for a broad range of medical diagnoses could explain apparent sex differences in incident dementia.
Study design and population
Researchers analyzed 53,224 members of a national nonprofit health maintenance organization who were dementia-free at baseline. Born between 1922 and 1946, participants entered the study on January 1, 2002 and were followed until January 1, 2020 (up to 18 years). Dementia diagnoses were obtained from electronic health records using standardized ICD codes, with diagnoses confirmed by geriatricians, neurologists, or psychiatrists.
Key findings: crude vs adjusted risk
At baseline, women accounted for a higher share of dementia cases (17.36%) than men (13.83%). In crude analyses, female sex appeared to be associated with a higher dementia risk (hazard ratio [HR] 1.08). However, when the model adjusted for background demographics and 33 medical conditions aggregated into ten medical domains, the sex difference disappeared (adjusted HR 1.02; not statistically significant).
Complementary analyses
When researchers separated the impact of specific medical domains, different patterns emerged. Adjusting for:
- Circulatory, respiratory, metabolic, digestive, or nervous system diseases, cancer, or injuries: females showed higher dementia risk than males, suggesting certain conditions magnify risk in women.
- Rheumatic and genitourinary diseases: the sex difference attenuated to null, indicating these conditions may underlie part of the crude female excess.
- Psychiatric disorders: interestingly, males showed higher risk once psychiatric conditions were accounted for, reversing the crude pattern.
Implications for research and prevention
These results imply that sex differences in dementia risk are not fixed and can be largely explained by medical history. This finding underscores the importance of controlling for a broad set of health conditions when investigating sex-specific dementia risk or testing prevention strategies. Public health approaches should consider how the prevalence of conditions like cardiovascular disease, hormonal and metabolic disorders, psychiatric conditions, and rheumatic/genitourinary diseases differ by sex and contribute to brain aging.
Biological and social considerations
sex differences in dementia have often been attributed to hormonal influences, genetic risk factors, and brain pathology. The new evidence emphasizes a complementary perspective: comorbidity patterns—shaped by gendered biology and life experiences—may drive observed disparities. For instance, cardiovascular disease often carries a larger dementia risk, and its greater impact in women in some analyses highlights potential sex-specific pathways. However, when broad medical histories are considered, the long-standing narrative of a female-only dementia risk becomes less certain, inviting more nuanced models that integrate medical history with sociodemographic factors.
Limitations and future directions
The study relies on electronic health records and diagnoses made in real-world clinical practice, which may miss subclinical conditions or vary in recording. The analysis did not distinguish dementia subtypes (e.g., Alzheimer’s vs vascular dementia), which could mask subtype-specific sex effects. Future research should explore how sex interacts with genetic risk, lifestyle factors, and longitudinal disease trajectories to tailor prevention and care for both sexes.
Takeaway for clinicians and policymakers
When assessing dementia risk by sex, clinicians should evaluate a patient’s comprehensive medical history, not only age or sex. Policymakers should support research and programs that address sex-specific comorbidity patterns and their influence on brain aging, ultimately refining strategies for prevention, early diagnosis, and intervention for all adults.
