BACKGROUND: Few studies comprehensively examined women's life-course reproductive patterns and the risk of dementia. This study aims to examine the association between women's reproductive life sequence and dementia, and to explore the potential role of intrinsic capacity (IC) on such association. METHODS: This study used data of 153,909 women who were post-menopause and free of dementia at baseline from the UK Biobank. We conducted sequence analysis and cluster analysis to identify women's life-course reproductive sequence and its potential patterns based on self-reported single reproductive factors. Women's IC at baseline comprised four functional domains: psychology, sensory, vitality, and locomotion. Participants were followed from baseline to the onset of dementia, death, or the end of follow-up (September 1, 2023). Fine and Gray's subdistribution hazard models were used to examine the associations between reproductive life sequences, IC, and dementia. RESULTS: During a median follow-up of 14.5 years, 2,940 dementia (including 1,509 Alzheimer's disease and 577 vascular dementia) cases were documented. Patterns of reproductive life sequences identified were: standard sequence (46.4%), early childbearing and oophorectomy menopause (6.5%), short reproductive span with natural menopause (17.7%), early childbearing and hysterectomy menopause (11.4%), and high parity with long birth span (18.1%). Compared to the standard sequence, short reproductive span with natural menopause (hazard ratio HR = 1.30, 95% confidence interval CI = 1.18-1.44), early childbearing and hysterectomy menopause (HR = 1.17, 95% CI = 1.04-1.32), and high parity with long birth span (HR = 1.13, 95% CI = 1.03-1.25) were associated with a higher risk of dementia. These associations would be strengthened when combining with IC impairment. For example, women with the combined sequence of short reproductive span with natural menopause and IC impairment had 2.40-fold (1.77-3.24) increased risk of dementia, compared to those with the standard sequence and no IC impairment. The associations between reproductive life patterns and dementia risk were stronger among women with more impairment items of IC. CONCLUSION: Our study showed cumulative associations of women's life-course reproductive factors with the risk of dementia in later life, and IC impairment could strengthen such associations. These results suggest the need to prioritize women with high-risk reproductive sequences, with special focus on their IC, in the prevention strategies for dementia.
Zhang et al. (Tue,) studied this question.