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

项目3的摘要 更年期在中年女性中是一种普遍的经历，但我们对即时 更年期过渡对大脑健康和认知的长期影响是有限的。一个关键组件 人类连接-老龄化项目(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。一份由210名年龄在40-59岁的女性组成的丰富样本提供了有关大脑的数据 结构、功能和连接性在两次访问中相隔约20个月。在老年成人脑连接组(AABC) 我们建议通过在220年的另外两次访问中获取这些相同的测量来极大地增强此数据集 女性，长达10年的所有更年期的纵向数据。在老龄化的成年人的大脑中 Connectome(AABC)我们建议通过在两个位置获取相同的测量来极大地增强此数据集 额外的访问，长达10年的所有更年期的纵向数据。AABC更年期 该项目反映了对认知老化和阿尔茨海默病及其相关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的作用的认识增加，如 雌二醇(E2)对大脑健康的影响。我们的重点是更年期各阶段的纵向变化轨迹(AIM 1)、更年期症状的作用(目标2)以及影响认知和恢复能力的脆弱性/复原力因素 女性生命中这个时期的大脑健康(目标3)。基于对世界各地认知变化的纵向研究 更年期，我们将重点放在围绝经期作为女性大脑健康的一个可能的拐点。我们的目标是 了解围绝经期记忆力下降的神经基础，并 了解雌二醇和更年期症状对这些变化的作用。认识到相当大的可变性 在绝经过渡期的认知主诉中，我们还旨在确定导致易感性的因素。 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)更年期 不仅使用金标准的出血标准，而且还使用FDA批准的新生物标记物(抗苗勒氏激素； AMH)(目标1)；2)评估报告的更年期症状以及血管舒缩的客观测量 使用可移动皮肤电导监测仪的症状(VMS)和活动监测睡眠(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弹性因素 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和 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，我们将跟踪220名年龄在40-59岁之间的女性，再进行两次神经成像检查。我们 将与其他项目和核心协同工作，以符合成本效益的方式实现研究目标。终极目标 这项工作的目的是为更年期如何影响认知老化的性别差异提供新的理解。 和ADRD，并为预防工作确定可能的可修改目标。

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.