Lee, Jillian K.

AbstractINTRODUCTIONFemale‐specific reproductive factors and exogeneous estrogen use are associated with cognition in later life. However, the underlying mechanisms are not understood. The present study aimed to investigate the effect of reproductive factors on neuroimaging biomarkers of Alzheimer's disease (AD) and cerebrovascular pathologies.METHODSWe evaluated 389 females (median age of 71.7 years) enrolled in the Mayo Clinic Study of Aging with reproductive history data and longitudinal magnetic resonance imaging (MRI) scans. We used linear mixed effect models to examine the associations between reproductive factors and changes in neuroimaging measures.RESULTSEver hormonal contraception (HC) use was longitudinally associated with higher fractional anisotropy across the corpus callosum, lower white matter hyperintensity (WMH) volume, and greater cortical thickness in an AD meta‐region of interest (ROI). The initiation of menopausal hormone therapy (MHT) > 5 years post menopause was associated with higher WMH volume.DISCUSSIONHC use and initiation of MHT >5 years post menopause were generally associated with neuroimaging biomarkers of cerebrovascular pathologies.Highlights Hormonal contraception use was associated with better brain white matter (WM) integrity. Initiation of menopausal hormone therapy >5 years post menopause was associated with worsening brain WM integrity. Hormonal contraception use was associated with greater cortical thickness. Ages at menarche and menopause and number of pregnancies were not associated with imaging measures. There were few associations between reproductive factors or exogenous estrogens and amyloid or tau PET.

AbstractINTRODUCTIONFew studies have comprehensively examined the impact of reproductive factors (i.e., reproductive window, parity, hormonal contraception [HC], and menopausal hormone therapy [MHT]) on global and domain‐specific cognition in later life.METHODSWe studied a population‐based sample of 2458 women (median age 74.2 years) residing in Olmsted County, Minnesota; participants underwent a clinical evaluation and comprehensive cognitive testing.RESULTSThe length of a woman's reproductive window was not associated with cognition. Higher parity was associated with greater cognitive decline in all domains. Ever HC use was associated with less decline in all domains. Ever MHT use was associated with greater decline in global cognition and all domain‐specific z‐scores except visuospatial; results were driven by women who initiated MHT 5 or more years after menopause. Additional adjustments for APOE and vascular‐related covariates did not attenuate the results.DISCUSSIONMultiple reproductive risk factors are associated with cognitive decline in later life.Highlights The length of a woman's reproductive window was not associated with cognition longitudinally. Greater parity was associated with greater cognitive decline longitudinally. Ever HC use was associated with less decline in global cognition and all domain‐specific z‐scores longitudinally (all p < 0.01). Ever MHT use was associated with greater decline in global cognition and all domain‐specific z‐scores except visuospatial longitudinally (all p < 0.01). The greatest cognitive decline was among women who initiated MHT more than 5 years after menopause.