Menstrual and reproductive factors and risk of Alzheimer’s disease in elderly women: a cohort study in Eastern China

Epidemiological studies suggest that proxies of lifetime estrogen exposure are associated with the risk of Alzheimer's disease (AD). However, results remain limited and inconsistent. This study aimed to examine whether menstrual and reproductive factors, proxies of estrogen exposure, are associated with the risk of AD in Chinese postmenopausal women. Information on menstrual and reproductive factors was obtained through the baseline survey of the Zhejiang Ageing and Health Cohort Study. During the three follow-up waves, AD diagnoses were conducted. We excluded participants with prevalent cognitive impairment or incomplete data of cognitive assessment at baseline, and incident cases of cognitive impairment without AD diagnosis across follow-up. Log-binomial model and the generalized additive model (GAM), controlled for a wide range of potential confounders, were generated to examine the association. Finally, 5606 women were included, and 597 developed AD during follow-up. The age of participants ranged from 60 to 95 years (mean = 65.7 years, SD = 6.5) at baseline. Women with a longer reproductive lifespan (> 34 years, compared with 32-34 years) had a lower risk of AD (RR = 0.81, 95% CI 0.67-0.98). Menopause due to ovariectomy was associated with a higher risk of AD (RR = 2.17, 95% CI 1.16-4.08), compared to those with natural menopause. The shorter length of menstrual cycles (≤ 27 days, compared with 28-30 days) was associated with an increased risk of AD (RR = 1.47, 95% 1.15-1.87), and shorter length of menstrual period (≤ 3 days, compared with 4-6 days) was associated with a decreased risk of AD (RR = 0.73, 95% 0.59-0.90). Women with 2 or more parity showed a higher risk of AD, while women with 2 or more miscarriages and abortions had a lower risk of AD. Older age at first childbirth (> 22 years, compared with 21-22 years) was associated with a decreased risk of AD (RR = 0.47, 95% CI 0.38-0.58). A U-shaped association was identified between mean breastfeeding duration and AD. Oral contraceptive use was also associated with an increased risk of AD. Our results show that menstrual and reproductive factors are statistically significantly associated with the risk of AD in Chinese postmenopausal women.