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

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.

Examine the relationship between reproductive and cognitive factors in both sexes, controlling for multiple covariates.

We analyzed data from 914 women with natural menopause (M^AGE = 72.65±5.57) and 811 men (M^AGE = 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.

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.

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.