From the Departments of Neurology (E.S., L.L., S.J., C.Z., G.J., N.M., H.H., S.P., R.I., H.K., L.M.) and Radiology (J.P.D., L.M.), Weill Cornell Medicine, New York, NY; Department of Pharmacology (R.D.B.), University of Arizona, Tucson.
Neurology. 2021 Dec 7;97(23):e2328-e2339. doi: 10.1212/WNL.0000000000012941. Epub 2021 Nov 3.
To examine associations between indicators of estrogen exposure from women's reproductive history and brain MRI biomarkers of Alzheimer disease (AD) in midlife.
We evaluated 99 cognitively normal women 52 ± 6 years of age and 29 men 52 ± 7 years of age with reproductive history data, neuropsychological testing, and volumetric MRI scans. We used multiple regressions to examine associations among reproductive history indicators, voxel-wise gray matter volume (GMV), and memory and global cognition scores, adjusting for demographics and midlife health indicators. Exposure variables were menopause status, age at menarche, age at menopause, reproductive span, hysterectomy status, number of children and pregnancies, and use of menopause hormonal therapy (HT) and hormonal contraceptives (HC).
All menopausal groups exhibited lower GMV in AD-vulnerable regions compared to men, with perimenopausal and postmenopausal groups also exhibiting lower GMV in temporal cortex compared to the premenopausal group. Reproductive span, number of children and pregnancies, and use of HT and HC were positively associated with GMV, chiefly in temporal cortex, frontal cortex, and precuneus, independent of age, ε4 status, and midlife health indicators. Although reproductive history indicators were not directly associated with cognitive measures, GMV in temporal regions was positively associated with memory and global cognition scores.
Reproductive history events signaling more estrogen exposure such as premenopausal status, longer reproductive span, higher number of children, and use of HT and HC were associated with larger GMV in women in midlife. Further studies are needed to elucidate sex-specific biological pathways through which reproductive history influences cognitive aging and AD risk.
探究女性生殖史中雌激素暴露指标与中年期阿尔茨海默病（AD）脑 MRI 生物标志物之间的关联。
我们评估了 99 名认知正常的女性（年龄 52 ± 6 岁）和 29 名男性（年龄 52 ± 7 岁），这些参与者均提供了生殖史数据、神经心理学测试和容积 MRI 扫描。我们使用多元回归分析，在校正人口统计学和中年健康指标后，考察生殖史指标与脑区灰质体积（GMV）以及记忆和整体认知评分之间的关联。暴露变量包括绝经状态、初潮年龄、绝经年龄、生殖期、子宫切除术状态、子女数量和妊娠次数，以及绝经激素治疗（HT）和激素避孕药（HC）的使用情况。
所有绝经组的 AD 易损区 GMV 均低于男性，围绝经期和绝经后组的颞叶 GMV 也低于绝经前组。生殖期、子女数量和妊娠次数，以及 HT 和 HC 的使用与 GMV 呈正相关，主要与颞叶、额叶和楔前叶有关，与年龄、ε4 状态和中年健康指标无关。尽管生殖史指标与认知测量无直接关联，但颞叶 GMV 与记忆和整体认知评分呈正相关。
提示雌激素暴露增加的生殖史事件，如绝经前状态、较长的生殖期、较多的子女数量，以及 HT 和 HC 的使用，与中年女性的 GMV 增大有关。需要进一步的研究来阐明生殖史通过何种特定的生物学途径影响认知老化和 AD 风险。
