Association between sex hormones and cognitive impairment in older adults aged 65 years and above in 18 longevity areas in China

Objective: To investigate the association between estradiol, testosterone levels, and cognitive impairment among older adults aged ≥65 years in 18 longevity-areas of China. Methods: This study utilized data from the cross-sectional survey of the 2021 China Healthy Ageing and Biomarkers Cohort Study. Information on socio-demographic characteristics, lifestyle, disease history, plasma estradiol, and testosterone levels was collected through face-to-face questionnaires, physical examinations, and laboratory tests. Cognitive function was assessed using the Mini-Mental State Examination, and cognitive impairment was defined based on education level. Multivariable logistic regression models were used to analyze the associations between sex hormones and cognitive impairment. Dose-response relationships were examined using restricted cubic splines, and subgroup analyses were performed to evaluate potential effect modifications. Results: A total of 5 721 older adults were included, of whom 1 653 (28.9%) had cognitive impairment. After adjusting for confounders, among males, each IQR increase in testosterone level was associated with a 16.5% decrease in the risk of cognitive impairment (OR=0.835, 95%CI: 0.718-0.971). Compared with the Q₁ group, the Q₃ (OR=0.668, 95%CI: 0.487-0.915) and Q₄ (OR=0.623, 95%CI: 0.444-0.870) groups showed a significantly lower risk, and a linear dose-response relationship was observed (P for overall=0.031). Among females, no statistically significant associations were found between estradiol or testosterone levels and cognitive impairment. Subgroup analyses showed that the associations between testosterone and cognitive impairment in older males were largely consistent across subgroups, with no statistically significant interactions detected. Conclusions: Among older males in 18 longevity areas of China, higher testosterone levels were independently associated with a lower risk of cognitive impairment. No significant associations were found among older females.