Association between reproductive history, white matter integrity, and cognition in post-menopausal Latina women from the Boston Latino Aging Study

Background: Women face disproportionately high Alzheimer’s disease (AD) rates, with Latina women experiencing particularly elevated cognitive impairment rates. Understanding reproductive factors’ impact on brain aging is critical for this underrepresented population. Given sex disparities in AD and reproductive factor influence on brain aging, we examined relations among reproductive history, white matter integrity, and cognitive function in post-menopausal Latina women. Methods: Participants were 95 post-menopausal Latina women from the Boston Latino Aging Study, mean age 65.7 (SD = 6.5) years and 11.7 (SD = 4.8) years of education. Reproductive history was obtained via self-report questionnaire. Cognitive assessment included Mini-Mental State Examination, Free and Cued Selective Reminding Test, Category Fluency, Story Memory Delayed Recall, and Symbol Digit Modalities Test administered in Spanish or Portuguese. White matter microstructure was assessed with diffusion weighted imaging using fixel-based methods. Regression models tested associations among reproductive factors, cognitive and imaging outcomes, adjusting for age, education, and cardiovascular risk. Mediation analyses evaluated whether white matter abnormalities explained reproductive-cognitive relations. Results: Pregnancy history was associated with worse delayed recall, with women having 1–2 (β = -0.79, p =.016) and 3–4 term pregnancies (β = -0.93, p =.005) performing worse than nulliparous women. Overall, hormone replacement therapy use was associated with better delayed recall (β = 0.58, p =.037). White matter analyses revealed trends suggesting pregnancy-related reductions in fiber density and cross-section across multiple tracts, with 3–4 term pregnancies showing most consistent patterns. Hysterectomy showed trends toward higher fiber density in several tracts. Mediation analyses indicated white matter integrity did not account for reproductive-cognitive associations. Conclusions: Reproductive history, particularly pregnancy number, is associated with cognitive performance and white matter microstructure in post-menopausal Latina women. These findings underscore the importance of considering reproductive factors in AD risk assessment and highlight the need for longitudinal studies to clarify mechanisms driving these associations.