Sex differences in the association between cardiovascular diseases and dementia subtypes: a prospective analysis of 464,616 UK Biobank participants

Abstract

Background Whether the association of cardiovascular diseases (CVDs) with dementia differs by sex remains unclear, and the role of socioeconomic, lifestyle, genetic, and medical factors in their association is unknown. Methods We used data from the UK Biobank, a population-based cohort study of 502,649 individuals. We used Cox proportional hazards models to estimate sex-specific hazard ratios (HRs) and 95% confidence intervals (CI), and women-to-men ratio of HRs (RHR) for the association between CVD (coronary heart diseases (CHD), stroke, and heart failure) and incident dementia (all-cause dementia, Alzheimer's Disease (AD), and vascular dementia (VD)). The moderator roles of socioeconomic (education, income), lifestyle (smoking, BMI, leisure activities, and physical activity), genetic factors (APOE allele status), and medical history were also analyzed. Results Compared to people who did not experience a CVD event, the HRs (95%CI) between CVD and all-cause dementia were higher in women compared to men, with an RHR (Female/Male) of 1.20 (1.13, 1.28). Specifically, the HRs for AD were higher in women with CHD and heart failure compared to men, with an RHR (95%CI) of 1.63 (1.39, 1.91) and 1.32 (1.07, 1.62) respectively. The HRs for VD were higher in men with heart failure than women, with RHR (95%CI) of 0.73 (0.57, 0.93). An interaction effect was observed between socioeconomic, lifestyle, genetic factors, and medical history in the sex-specific association between CVD and dementia. Conclusion Women with CVD were 1.5 times more likely to experience AD than men, while had 15% lower risk of having VD than men.

Associations between abdominal adipose tissue, reproductive span, and brain characteristics in post-menopausal women

“…Recent studies also point towards a biphasic association between BMI and dementia ( Kivimäki et al, 2018 , Pedditizi et al, 2016 ). For example, while midlife obesity predicts risk for dementia ( Albanese et al, 2017 , Floud et al, 2020 , Pedditizi et al, 2016 ), the prevalence of dementia has been found to be higher in underweight than in normal weight or overweight females ( Dong et al, 2022 ). Prodromal stages of neurodegenerative diseases can involve weight loss as a result of disrupted brain function and dietary changes ( Floud et al, 2020 , Gu et al, 2014 ), and longitudinal studies targeting early markers of neurodegeneration may further the understanding of changes in body weight, brain health, and dementia risk in females.…”

Associations between abdominal adipose tissue, reproductive span, and brain characteristics in post-menopausal women

“…Recent studies also point towards a biphasic association between BMI and dementia (Kivimäki et al, 2018;Pedditizi et al, 2016). For example, while midlife obesity predicts risk for dementia (Albanese et al, 2017;Floud et al, 2020;Pedditizi et al, 2016), the prevalence of dementia has been found to be higher in underweight than in normal weight or overweight females (Dong et al, 2022). Prodromal stages of neurodegenerative diseases can involve weight loss as a result of disrupted brain function and dietary changes (Floud et al, 2020;Gu et al, 2014), and longitudinal studies targeting early markers of neurodegeneration may further the understanding of changes in body weight, brain health, and dementia risk in females.…”

“…The associations between adipose tissue and female brain health post-menopause may further depend on the individual's lifetime exposure to oestrogens. Studies indicate that levels of cumulative oestrogen exposure, often assessed by reproductive span (age at menarche to age at menopause; (Fu et al, 2022;Gilsanz et al, 2019;Jett et al, 2022)), have lasting effects on brain structure and body composition even after menopause. For example, a longer reproductive span has been linked to larger GM volumes (Schelbaum et al, 2021), lower WM brain age (Subramaniapillai et al, 2022), and lower dementia risk in older-age samples (Fox et al, 2013;Gilsanz et al, 2019;Gong et al, 2022), although contrasting results have linked a longer reproductive span to increased risk of Alzheimer's disease (AD) (Najar et al, 2020;Geerlings et al, 2001).…”

Sex/gender and socioeconomic differences in modifiable risk factors for dementia

“…Furthermore, obesity was associated with an increased dementia risk among women, but a decreased dementia risk among men. Another UK Biobank study found that women with cardiovascular disease had a 20% increased risk for dementia compared to men with cardiovascular disease 13 .…”