From the Population Health Sciences (V.L., G.P., G.S., M.M.B.B.), and Statistics and Machine Learning (A.M.), German Center for Neurodegenerative Diseases (DZNE), Bonn; J. Philip Kistler Stroke Research Center (M.D.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Clinic for Neuroradiology (M.D.S.), University Hospital Bonn, Germany; MR Physics (T.S.), German Center for Neurodegenerative Diseases (DZNE), Bonn; Department of Physics and Astronomy (T.S.), University of Bonn, Germany; Image Analysis (M.R.), German Center for Neurodegenerative Diseases (DZNE), Bonn; A.A. Martinos Center for Biomedical Imaging (M.R.), Massachusetts General Hospital, Boston; Department of Radiology (M.R.), Harvard Medical School, Boston, MA; and Institute for Medical Biometry (M.M.B.B.), Informatics and Epidemiology (IMBIE), Faculty of Medicine, University of Bonn, Germany.
Neurology. 2022 Aug 30;99(9):e935-e943. doi: 10.1212/WNL.0000000000200782. Epub 2022 Jun 29.
Mounting evidence implies that there are sex differences in white matter hyperintensity (WMH) burden in older people. Questions remain regarding possible differences in WMH burden between men and women of younger age, sex-specific age trajectories and effects of (un)controlled hypertension, and the effect of menopause on WMH. Therefore, our aim was to investigate these sex differences and age dependencies in WMH load across the adult life span and to examine the effect of menopause.
This cross-sectional analysis was based on participants of the population-based Rhineland Study (30-95 years) who underwent brain MRI. We automatically quantified WMH using T1-weighted, T2-weighted, and fluid-attenuated inversion recovery images. Menopausal status was self-reported. We examined associations of sex and menopause with WMH load (logit-transformed and -standardized) using linear regression models while adjusting for age, age-squared, and vascular risk factors. We checked for an age × sex and (un)controlled hypertension × sex interaction and stratified for menopausal status comparing men with premenopausal women (persons aged 59 years or younger), men with postmenopausal women (persons aged 45 years or older), and premenopausal with postmenopausal women (age range 45-59 years).
Of 3,410 participants with a mean age of 54.3 years (SD = 13.7), 1,973 (57.9%) were women, of which 1,167 (59.1%) were postmenopausal. We found that the increase in WMH load accelerates with age and in a sex-dependent way. Premenopausal women and men of similar age did not differ in WMH burden. WMH burden was higher and accelerated faster in postmenopausal women compared with men of similar age. In addition, we observed changes related to menopause, in that postmenopausal women had more WMH than premenopausal women of similar age. Women with uncontrolled hypertension had a higher WMH burden compared with men, which was unrelated to menopausal status.
After menopause, women displayed a higher burden of WMH than contemporary premenopausal women and men and an accelerated increase in WMH. Sex-specific effects of uncontrolled hypertension on WMH were not related to menopause. Further studies are warranted to investigate menopause-related physiologic changes that may inform on causal mechanisms involved in cerebral small vessel disease progression.
越来越多的证据表明，老年人的脑白质高信号（WMH）负担存在性别差异。但关于年龄较轻的男性和女性之间 WMH 负担的可能差异、性别特异性年龄轨迹以及（未）控制高血压的影响，以及绝经期对 WMH 的影响等问题仍存在疑问。因此，我们的目的是研究整个成年期 WMH 负荷的这些性别差异和年龄依赖性，并探讨绝经期的影响。
本横断面分析基于参加人群为基础的莱茵兰研究（30-95 岁）的参与者，他们接受了脑部 MRI 检查。我们使用 T1 加权、T2 加权和液体衰减反转恢复图像自动量化 WMH。绝经期状态由自我报告。我们使用线性回归模型检查性别和绝经期与 WMH 负荷（对数转换和标准化）之间的关联，同时调整年龄、年龄平方和血管危险因素。我们检查了年龄×性别和（未）控制高血压×性别之间的相互作用，并根据绝经期状态进行分层，比较了绝经前女性（年龄 59 岁或以下的人）与男性、绝经后女性（年龄 45 岁或以上的人）与男性、以及绝经前女性与绝经后女性（年龄 45-59 岁）之间的差异。
在 3410 名平均年龄为 54.3 岁（标准差=13.7）的参与者中，1973 名（57.9%）为女性，其中 1167 名（59.1%）为绝经后女性。我们发现，WMH 负荷的增加随着年龄的增长而加速，并且具有性别依赖性。绝经前女性和同龄男性的 WMH 负担没有差异。与同龄男性相比，绝经后女性的 WMH 负担更高，且增加速度更快。此外，我们观察到与绝经相关的变化，即绝经后女性的 WMH 比同龄的绝经前女性更多。未控制高血压的女性的 WMH 负担高于男性，但与绝经状态无关。
需要进一步的研究来探讨与绝经相关的生理变化，这些变化可能为脑小血管疾病进展中涉及的因果机制提供信息。
