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

更年期过渡对大脑结构、功能和认知的影响

• 批准号: 10283070
• 负责人: PAULINE M MAKI
• 金额: $ 17.89万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10283070
• 关键词: Address; Adult; Affect; Age; Age-Years; Aging; Alzheimer' s Disease; Alzheimer' s disease patient; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amyloid beta-42; Biological Markers; Brain; Brain imaging; Cognition; Cognitive; Cognitive aging; Data; Data Set; Disease Marker; Estradiol; FDA approved; Face; Female; Galvanic Skin Response; Goals; Gold; Gonadal Steroid Hormones; Health; Hemorrhage; Hippocampus (Brain); Hormones; Hot flushes; Human; Hyperactivity; Inflammation; Life; Link; Longitudinal Studies; Measures; Mediating; Memory; Memory Loss; Menopausal Symptom; Menopause; Menstruation; Monitor; Names; Night Sweating; Operative Surgical Procedures; Patient Self-Report; Performance; Perimenopause; Phase Transition; Plasma; Postmenopause; Prefrontal Cortex; Prevention; Recording of previous events; Reporting; Rest; Role; Sampling; Sex Differences; Sleep; Structure; Symptoms; System; Time; Vasomotor; Visit; Woman; Work; actigraphy; aged; allostatic load; base; brain dysfunction; brain health; cognitive change; connectome; cost effective; experience; experimental study; genetic risk factor; insight; lifestyle factors; middle age; modifiable risk; mullerian-inhibiting hormone; neurochemistry; neuroimaging; phase change; relating to nervous system; reproductive senescence; resilience; response; tau-1

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.

项目3摘要 更年期是生活到中年的妇女中的普遍经历，但我们对即时的理解 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 人类连接仪项目（HCP-Aging）的能力是收集大脑和认知数据的能力 整个更年期阶段。 210名40-59岁女性的丰富样本提供了有关大脑的数据 两次访问时的结构，功能和连通性相距约20个月。在老化的成人脑连接组（AABC）中 我们建议通过在220的另外两次访问中获得相同的措施来大大增强该数据集 在所有更年期阶段，妇女最多可以使用10年的纵向数据。在成年大脑中 Connectome（AABC）我们建议通过在两个处获得相同的措施来大大增强该数据集 在所有更年期阶段，最多10年的纵向数据进行了额外的访问。 AABC Menopaus 项目反映了对认知衰老和阿尔茨海默氏病的性别差异的越来越多的认识以及相关的 痴呆症（ADRD），并增加对更年期和性类固醇激素的作用的欣赏 关于大脑健康的雌二醇（E2）。我们的重点是整个更年期阶段变化的纵向轨迹（目标 1），更年期症状的作用（AIM 2）以及影响认知和的脆弱性/韧性因素 在女性生活中的这个时候，大脑健康（AIM 3）。基于对整个认知变化的纵向研究 更年期，我们将重点放在围绝经期是女性大脑健康中的可能性拐点。我们的目标 了解有据可查的记忆下降的神经基础，并在围栏中发生，并 了解E2和更年期症状在这些变化中的作用。认识到很大的可变性 在更年期过渡中的认知投诉中，我们还旨在确定赋予脆弱性的因素 以及对这些变化的韧性。为此，我们建议向AABC添加新措施：1）阶段更年期 不仅使用金色标准的出血标准，还使用新的FDA批准的生物标志物（抗Müllerian激素； AMH）（目标1）; 2）评估报道的更年期症状以及血管舒缩的客观测量 带有卧床皮肤电导监测器的症状（VM），并带有表观摄影的睡眠（AIM 2）； 3）工作 与其他项目和核心一起检查脆弱性和弹性因素以影响认知和大脑 健康（目标3）。我们还将提供有关AD生物标志物如何随年阶段变化的关键见解和 症状以及AD遗传危险因素如何影响中年认知和大脑变化的轨迹。到 实现这些目标，我们将在另外两次神经影像访问中跟随220名40-59岁的女性。我们 将以具有成本效益的方式与其他项目和核心协同实现该研究的目标。最终目标 这项工作是对更年期如何促进认知衰老的性别差异的新理解 和ADRD，并确定可能修改的预防努力目标。