Sex-specific associations between reproductive history and late-life cognitive outcomes

BACKGROUND: Reproductive factors have been associated with cognition in older women, yet findings have been inconsistent. Moreover, recent studies have also found similar associations in men. OBJECTIVE: Examine the relationship between reproductive and cognitive factors in both sexes, controlling for multiple covariates. METHODS: We analyzed data from 914 women with natural menopause (MAGE = 72.65±5.57) and 811 men (MAGE = 74.43±5.37) from the HELIAD study. Participants provided reproductive, medical, and social histories and had a comprehensive neuropsychological assessment, including Mild Cognitive Impairment and dementia diagnosis. Covariates included age, education, medical, genetic, lifestyle, and socioeconomic factors. RESULTS: Controlling for age and education, in women, later menarche, earlier menopause, fewer menstrual years, shorter interpregnancy intervals, and menstrual regularity were associated with poorer cognitive outcomes. Earlier first childbirth (<25y), greater parity (especially, before 20y), and older age at fourth childbirth were linked to better cognition (ORs:.95-2.20). In men, older age at third and fourth child birth, having more children at ages 20-29 or 40+, the last child at >35y, and childlessness were associated with poorer cognition, while having the first child at >35y (language tasks) and having more children overall were associated with better cognition (ORs:1.37-2.20). After full-adjustment and Bonferroni correction, no associations remained. CONCLUSIONS: Reproductive patterns may affect cognition differentially based on sex. Moderate reproductive activity may be protective, whereas extreme patterns (e.g. very early/late childbirth, childlessness) may be linked to cognitive decline. These associations attenuate after statistical adjustment and correction, necessitating further controlled and longitudinal studies to clarify these relationships.