EFFECTS OF MENOPAUSE TRANSITION ON BRAIN STRUCTURE, FUNCTION, AND COGNITION

项目 3 摘要 更年期是中年女性的普遍经历，但我们对眼前的情况的理解 更年期过渡对大脑健康和认知的长期影响有限。关键部件 人类连接组老化项目（HCP-Aging）的核心是收集大脑和认知数据的能力 跨越更年期阶段。 210 名 40-59 岁女性的丰富样本提供了有关大脑的数据 两次访问的结构、功能和连接性~相隔 20 个月。在衰老的成人大脑连接组 (AABC) 中 我们建议通过在 220 年的两次额外访问中获取相同的测量值来极大地增强该数据集 女性，涵盖所有更年期阶段长达 10 年的纵向数据。在衰老的成人大脑中 Connectome (AABC) 我们建议通过在两个位置获取相同的测量值来极大地增强该数据集 额外访问，获取所有更年期阶段长达 10 年的纵向数据。 AABC 更年期 该项目反映了人们对认知衰老和阿尔茨海默氏病及相关疾病中性别差异的认识不断提高 痴呆症（ADRD），以及对更年期和性类固醇激素（如 雌二醇（E2）对大脑健康的影响。我们的重点是更年期各个阶段变化的纵向轨迹（目标 1）、更年期症状的作用（目标 2）以及影响认知和能力的脆弱性/弹性因素 女性一生中此时的大脑健康（目标 3）。基于对整个认知变化的纵向研究 更年期，我们将围绝经期视为女性大脑健康可能的拐点。我们的目标是 了解围绝经期发生的有据可查的记忆衰退的神经基础，并 了解 E2 和更年期症状对这些变化的作用。认识到相当大的可变性 在更年期过渡期间的认知问题中，我们还旨在确定导致脆弱性的因素 以及对这些变化的适应能力。为此，我们建议在AABC中增加新的措施：1）阶段性更年期 不仅使用金标准出血标准，还使用 FDA 批准的新生物标志物（抗苗勒氏管激素； AMH）（目标 1）； 2）评估报告的更年期症状以及血管舒缩的客观指标 使用动态皮肤电导监测仪监测症状 (VMS)，并使用体动记录仪监测睡眠（目标 2）； 3）工作 与其他项目和核心一起检查影响认知和大脑的脆弱性和复原力因素 健康（目标 3）。我们还将提供有关 AD 生物标志物如何随更年期阶段变化的重要见解，以及 症状，以及 AD 遗传风险因素如何影响中年认知和大脑变化的轨迹。至 为了实现这些目标，我们将在另外两次神经影像检查中跟踪 220 名 40-59 岁的女性。我们 将与其他项目和核心协同作用，以具有成本效益的方式实现研究目标。最终目标 这项工作的目的是提供对更年期如何影响认知衰老的性别差异的新认识 ADRD，并确定预防工作可能的可修改目标。

ABSTRACT FOR PROJECT 3 Menopause is a universal experience among women living to midlife, yet our understanding of the immediate and long-term influence of the menopause transition on brain health and cognition is limited. A key component of the Human Connectome-Aging Project (HCP-Aging) has been the ability to collect brain and cognitive data across menopause stages. An enriched sample of 210 women aged 40-59 years provides data on brain structure, function and connectivity at two visits ~ 20 months apart. In the Aging Adult Brain Connectome (AABC) we propose to greatly enhance this dataset by acquiring those same measures at two additional visits in 220 women, for up to 10 years of longitudinal data across all menopause stages. In the Aging Adult Brain Connectome (AABC) we propose to greatly enhance this dataset by acquiring those same measures at two additional visits, for up to 10 years of longitudinal data across all menopause stages. The AABC Menopause Project reflects increased recognition of sex differences in cognitive aging and Alzheimer's disease and related dementias (ADRD), and increased appreciation for the role of menopause and sex steroid hormones like estradiol (E2) on brain health. Our focus is on longitudinal trajectories of change across menopause stages (Aim 1), the role of menopause symptoms (Aim 2), and the vulnerability/resilience factors that influence cognition and brain health at this time in a woman's life (Aim 3). Based on longitudinal studies of cognitive changes across the menopause, we focus on the perimenopause as a likely inflection point in women's brain health. We aim to understand the neural basis of the well-documented memory declines that occur in the perimenopause, and to understand the role of E2 and menopause symptoms on these changes. Recognizing the considerable variability in cognitive complaints in the menopause transition, we also aim to determine the factors that confer vulnerability and resilience to those changes. To this end, we propose to add new measures to AABC to: 1) stage menopause not only using gold-standard bleeding criteria but also a new FDA-approved biomarker (anti-Müllerian hormone; AMH) (Aim 1); 2) assess reported menopausal symptoms, as well as objective measures of vasomotor symptoms (VMS) with ambulatory skin conductance monitors and sleep with actigraphy (Aim 2); and 3) work with other projects and cores to examine vulnerability and resilience factors to influence cognition and brain health (Aim 3). We will also provide key insights into how AD biomarkers change with menopause stage and symptoms, and how AD genetic risk factors influence the trajectory of cognitive and brain changes at midlife. To achieve these goals, we will follow 220 women age 40-59 years of age at two additional neuroimaging visits. We will synergize with other projects and cores to meet the study aims in a cost-effective manner. The ultimate goal of this work is to provide new understanding of how menopause contributes to sex differences in cognitive aging and ADRD, and to identify possible modifiable targets for prevention efforts.