Menopausal Vasomotor Symptoms and Brain Aging in Women

女性更年期血管舒缩症状和大脑老化

• 批准号: 10654010
• 负责人: PAULINE M MAKI
• 金额: $ 77.34万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-15 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10654010
• 关键词: Acceleration; Adult; Affect; Age; Aging; Alleles; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease risk; Ambulatory Monitoring; Apolipoproteins; Atherosclerosis; Back; Basic Science; Benign; Blood; Brain; Brain imaging; Cardiovascular Diseases; Cardiovascular system; Carotid Atherosclerotic Disease; Cognition; Cognitive; Complex; Data; Dementia; Diagnosis; Disease; Early Intervention; Enrollment; Estradiol; Estrogens; Estrone; Event; Female; Functional disorder; Funding; Goals; Gonadal Steroid Hormones; Health; Hippocampus; Hormonal; Hormonal Change; Impaired cognition; Link; Magnetic Resonance Imaging; Measurement; Measures; Memory; Menopausal Symptom; Menopause; Mitochondria; Morphology; Natural History; Neuropsychological Tests; Neuropsychology; Outcome; Participant; Performance; Physiological; Postmenopause; Reporting; Research; Rest; Risk; Risk Factors; Risk Reduction; Role; Sampling; Science; Sleep; Sleep Disorders; Sleep disturbances; Structure; Symptoms; Testing; Time; Ultrasonography; Venous blood sampling; White Matter Hyperintensity; Woman; Work; actigraphy; aging brain; brain health; cardiovascular disorder risk; cardiovascular health; cardiovascular risk factor; cognitive change; cognitive function; cognitive performance; cognitive testing; cohort; cost; high risk; improved; lifetime risk; longitudinal design; meetings; member; men; middle age; mild cognitive impairment; neuropathology; novel; older women; persistent symptom; poor sleep; recruit; sex; sleep health; ultrasound; vasomotor symptoms

Identifying risk factors for cognitive change early in the natural history of Alzheimer's disease (AD) is critical, as there is yet no cure for the disease. The lifetime risk of AD is higher in women than men, yet few studies have identified female-related risk factors for the disease. The menopause is a universal event in women and affects cognitive and brain health. In addition to hormonal changes, the menopause is accompanied by vasomotor symptoms (VMS) and sleep problems. Over 70% of midlife women report VMS, and for a third of women, VMS are persistent for over a decade, well into the 60s. Further, half of women report poor sleep at menopause. Few studies have examined the effect of VMS on brain health, particularly during sleep (sleep VMS). Informed by our novel pilot work showing links of sleep VMS to brain health and the growing understanding of the negative effect of poor sleep on brain health and AD pathology, the MsBrain I study focused on VMS and sleep disturbance, persistent symptoms tied to risk factors for AD including cardiovascular disease (CVD). Our initial MsBrain I findings indicate that objectively-assessed sleep VMS (measured with state-of-the-art ambulatory monitors) as well as poor sleep (measured with actigraphy) are associated with worse cognitive function and adverse indicators of brain structure and function. Sex steroid hormones do not explain these associations. In MsBrain II, we propose to test VMS and poor sleep as risk factors for adverse changes in brain and cognitive health among 160 MsBrain I participants (current mean age=60 years). Our primary aim is to leverage a longitudinal design to test whether a greater burden of objectively-assessed menopausal symptoms (sleep VMS, poor sleep) assessed up to three times over ten years is associated with declines brain and cognitive health over time. We will test the role of estrogens and CVD risk in the relationships of sleep VMS and sleep to brain and cognitive health. This aim recognizes the complex interplay among risk factors for cognitive impairment, with a focus on factors that change with menopause. Further, a wealth of basic science shows menopause-induced changes in mitochondrial function that contribute to adverse brain changes. Our pilot data finds VMS and sleep related to altered mitochondrial function. Our third aim tests the relations of mitochondrial function to brain health and the role of mitochondrial function in links between VMS, sleep, and brain health. To achieve these aims, we will invite 160 MsBrain I participants back to repeat objective assessments of VMS and sleep, as well as CVD risk factor assessment, carotid ultrasound imaging, sex hormone measurement, blood- based measures of mitochondrial function, and neuropsychological testing. To advance this science, we will extend our brain imaging work to leverage state-of-the-art 7 Tesla (7T) magnetic resonance imaging to assess brain structure and function. Findings from this study will determine whether VMS and poor sleep can be identified as markers for midlife women at risk of cognitive decline. The ultimate goal of this work is to assist in early intervention efforts to improve cognition, enhance brain reserve, and reduce AD risk in aging women.

在阿尔茨海默病（AD）自然史的早期识别认知变化的风险因素至关重要， 这种疾病还没有治愈的方法。女性AD的终生风险高于男性，但很少有研究表明， 确定了与女性相关的疾病风险因素。更年期是女性的一个普遍事件， 认知和大脑健康。更年期除了激素变化外，还伴随着血管痉挛 症状（VMS）和睡眠问题。超过70%的中年妇女报告VMS，三分之一的妇女，VMS 持续了十多年，一直持续到60年代此外，一半的女性报告在更年期睡眠不好。 很少有研究探讨VMS对大脑健康的影响，特别是在睡眠期间（睡眠VMS）。知情 我们的新试点工作显示了睡眠VMS与大脑健康的联系， 睡眠不良对大脑健康和AD病理学的负面影响，MsBrain I研究重点是VMS和睡眠 这些症状包括心血管疾病（CVD）和与AD风险因素相关的持续性症状。我们最初 MsBrain I研究结果表明，客观评估的睡眠VMS（使用最先进的动态 监测器）以及睡眠不佳（用活动记录仪测量）与认知功能较差有关， 大脑结构和功能的不良指标。性类固醇激素不能解释这些联系。在 MsBrain II，我们建议测试VMS和睡眠不良作为大脑和认知功能不良变化的风险因素， 160名MsBrain I参与者（当前平均年龄=60岁）的健康状况。我们的主要目标是利用 纵向设计，以测试是否更大的负担，客观评估的更年期症状（睡眠 VMS，睡眠不好）在十年内评估多达三次与大脑和认知能力下降有关 随着时间的推移健康。我们将测试雌激素和心血管疾病风险在睡眠VMS和睡眠之间的关系中的作用， 大脑和认知健康。这一目标认识到认知障碍风险因素之间的复杂相互作用， 损伤，重点是随着更年期的变化而变化的因素。此外，大量的基础科学研究表明， 更年期引起的线粒体功能变化，导致不利的大脑变化。我们的试点数据 发现VMS和睡眠与线粒体功能改变有关。我们的第三个目的是测试线粒体的关系， 功能对大脑健康的影响以及线粒体功能在VMS，睡眠和大脑健康之间的联系中的作用。到 为了实现这些目标，我们将邀请160名MsBrain I参与者再次对VMS进行客观评估， 睡眠，以及心血管疾病危险因素评估，颈动脉超声成像，性激素测量，血液- 基于线粒体功能的测量和神经心理学测试。为了推进这项科学，我们将 扩展我们的大脑成像工作，利用最先进的7特斯拉（7 T）磁共振成像来评估 大脑结构和功能这项研究的结果将确定VMS和睡眠不良是否会 被认为是中年女性认知能力下降的标志。这项工作的最终目标是协助 早期干预努力，以改善认知，增强大脑储备，并降低老年妇女的AD风险。

项目成果

Menopausal vasomotor symptoms and adiponectin among midlife women.

中年女性的更年期血管舒缩症状和脂联素。

• DOI: 10.1097/gme.0000000000002039
• 发表时间: 2022
• 期刊: Menopause (New York, N.Y.)
• 作者: Thurston,RebeccaC;Chang,Yuefang
• 通讯作者: Chang,Yuefang

Menopausal Vasomotor Symptoms and White Matter Hyperintensities in Midlife Women.

中年女性的更年期血管舒缩症状和白质高信号。

• DOI: 10.1212/wnl.0000000000201401
• 发表时间: 2023
• 期刊: Neurology
• 影响因子: 9.9
• 作者: Thurston,RebeccaC;Wu,Minjie;Chang,Yue-Fang;Aizenstein,HowardJ;Derby,CarolA;Barinas-Mitchell,EmmaA;Maki,Pauline
• 通讯作者: Maki,Pauline

Astrocyte reactivity influences the association of amyloid-β and tau biomarkers in preclinical Alzheimer's disease.

星形胶质细胞反应性影响临床前阿尔茨海默病中淀粉样蛋白-β 和 tau 生物标志物的关联。

• DOI: 10.21203/rs.3.rs-2507179/v1
• 发表时间: 2023
• 期刊: Research square
• 作者: Pascoal,Tharick;Bellaver,Bruna;Povala,Guilherme;Ferreira,Pamela;Ferrari-Souza,JoãoPedro;Leffa,Douglas;Lussier,Firoza;Benedet,Andrea;Ashton,Nicholas;Triana-Baltzerz,Gallen;Kolbzh,Hartmuth;Tissot,Cèile;Therriault,Joseph;Servaes,S
• 通讯作者: Servaes,S

Menopause and Brain Health: Hormonal Changes Are Only Part of the Story.

• DOI: 10.3389/fneur.2020.562275
• 发表时间: 2020
• 期刊: Frontiers in neurology
• 影响因子: 3.4
• 作者: Maki PM;Thurston RC
• 通讯作者: Thurston RC

Sleep Characteristics and White Matter Hyperintensities Among Midlife Women.

• DOI: 10.1093/sleep/zsz298
• 发表时间: 2019-12
• 期刊: Sleep
• 影响因子: 5.6
• 作者: R. Thurston;Minjie Wu;H. Aizenstein;Yuefang Chang;Emma Barinas Mitchell;C. Derby;P. Maki