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

项目3摘要 更年期是一个普遍的经验，妇女生活到中年，但我们的理解，直接 更年期对大脑健康和认知的长期影响是有限的。一个关键组成部分 人类连接体老化项目（HCP-Aging）的一项重要成果是能够收集大脑和认知数据， 在绝经期的各个阶段。210名年龄在40-59岁之间的女性的丰富样本提供了大脑的数据 结构、功能和连通性，两次访视间隔约20个月。老年成人脑连接组（AABC） 我们建议通过在220年的另外两次访问中获得相同的测量结果来大大增强该数据集 妇女，在所有更年期阶段长达10年的纵向数据。在老化的成人大脑中 连接组（AABC），我们建议通过在两个 额外的访问，长达10年的纵向数据，在所有更年期阶段。AABC更年期 项目反映了对认知老化和阿尔茨海默病及相关疾病的性别差异的认识增加 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。我们的重点是跨绝经阶段的纵向变化轨迹（Aim 1），更年期症状的作用（目标2），以及影响认知和 在这个时候在一个女人的生活（目标3）的大脑健康。基于对整个国家认知变化的纵向研究， 更年期，我们关注围绝经期作为女性大脑健康的一个可能的转折点。我们的目标是 了解在围绝经期发生的记忆力下降的神经基础，并 了解E2和更年期症状在这些变化中的作用。认识到各种因素 在更年期的认知障碍中，我们也致力于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“更年期综合征”中加入以下新措施： 不仅使用黄金标准出血标准，而且使用FDA批准的新生物标志物（抗苗勒管激素; AMH）（目的1）; 2）评估报告的绝经期症状，以及血管扩张的客观指标 症状（VMS）与动态皮肤电导监测仪和睡眠与体动仪（目的2）;和3）工作 与其他项目和核心一起研究影响认知和大脑的脆弱性和弹性因素 健康（目标3）。我们还将提供关于AD生物标志物如何随绝经阶段变化的关键见解， 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。到 为了实现这些目标，我们将对220名年龄在40-59岁之间的女性进行两次额外的神经影像学随访。我们 我们会与其他项目和核心项目互相配合，以符合成本效益的方式达致研究目的。最终目标 这项工作的目的是提供新的理解更年期如何有助于认知老化的性别差异 和ADRD，并确定预防工作的可能修改目标。

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.