Role of estradiol and related hormones on inflammation, sleep, and risks for Alzheimer's disease

雌二醇和相关激素对炎症、睡眠和阿尔茨海默病风险的作用

• 批准号: 10458043
• 负责人: William Tzu-lung Hu
• 金额: $ 71.24万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10458043
• 关键词: Affect; African American; African American population; Age; Aging; Alleles; Alzheimer' s Disease; Alzheimer' s disease brain; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amyloid beta-Protein; Amyloid deposition; Animal Experimentation; Biological Markers; Biometry; Blood; Blood - brain barrier anatomy; Blood Volume; Blood flow; Brain; Brain imaging; Caucasians; Cerebrospinal Fluid; Cerebrovascular Circulation; Cerebrum; Clinical Trials; Cognition; Cognitive; Collection; Cytokine Signaling; Data; Enrollment; Estradiol; Estrogens; Estrone; Exercise; Family; Funding; Gonadal Steroid Hormones; High Risk Woman; Home; Hormonal; Hormones; IL7 gene; Image; Individual; Inflammation; Inflammatory; Intervention; Life; Life Expectancy; Link; Longevity; Magnetic Resonance Imaging; Measures; Medical; Menarche; Menopause; Menstruation; Nerve Degeneration; Outcome; Participant; Perfusion; Perimenopause; Peripheral; Pharmaceutical Preparations; Phenotype; Plasma; Polysomnography; Postmenopausal Osteoporosis; Pregnancy; Progesterone; Prospective Studies; Protocols documentation; Questionnaires; Race; Recording of previous events; Research; Research Personnel; Risk; Risk Factors; Role; Sampling; Serum; Sleep; Sleep Disorders; Sleep disturbances; Slow-Wave Sleep; Spinal Puncture; Stress; Structure; Testing; Testosterone; United States National Institutes of Health; Visit; Woman; angiogenesis; apolipoprotein E-4; base; biomarker-driven; brain volume; cognitive testing; cohort; high risk; hormone therapy; hypocretin; inflammatory marker; men; middle age; multidisciplinary; neuroimaging; neuroprotection; non-invasive monitor; nutrition; poor sleep; prospective; racial diversity; recruit; sleep quality; tau Proteins; white matter

Women are more likely than men to develop Alzheimer's disease (AD), and available research suggests this is not only because they have a longer life expectancy than men. This increased risk is likely due, in part, to fluctuating sex hormones across the lifespan. Sex hormones likely have direct actions on AD brain biomarkers (Aβ and tau levels), as well as indirect actions via inflammation, sleep disruptions, and reduced brain blood flow and volume, all of which are independent risk factors for AD. African Americans –men and women– are also at increased risk for AD vs. Caucasians. As such, mechanistic studies and interventions need to be thoroughly examined and tested in both African American and Caucasian participants. The purpose of the proposed project is to determine the relationship between brain and systemic sex hormones on known AD biomarkers in individuals most at risk for AD. 150 middle age, African American (n=75) and Caucasian (n=75) women will be enrolled in this observational, two year study. The main objectives are to test whether brain and serum sex hormones (estradiol, estrone, progesterone, testosterone) differentially influence AD risk factors (inflammation, sleep and cerebral blood flow,), and if sex hormone levels moderate the relationship between these risk factors and AD biomarkers (cognition, CSF, neuro-imaging). We will leverage existing NIH funded, well characterized cohorts (n=291; followed by MPIs Wharton & Hu), including middle- age women at high risk for AD (through family history or APOE e4 allele) who already have baseline and longitudinal blood, CSF, and MRI analysis for at least 2 years. We will also test our hypotheses in a unique cohort enriched for African Americans based on our extensive track record in recruiting and analyzing aging and AD biomarkers in a diverse cohort. Participants will complete 3 study visits annually. At each year, we will collect medical and medication history, subjective sleep, cognitive testing and questionnaires (stress, sleep, exercise, nutrition) Participants also undergo blood draw for sex hormone and inflammatory markers. At Baseline and Year 2, participants will undergo the aforementioned protocol, AND take part in: lumbar puncture for spinal fluid collection, neuroimaging and will take home a non-invasive monitor for collection of objective sleep data to wear for 1 night. We have assembled a multidisciplinary team with complementary expertise in sex hormones and aging, AD biomarkers, inflammation, neuroimaging, sleep, and biostatistics. Data inform larger NIH funded studies and, to our knowledge, provide the largest and most comprehensive, biomarker driven, characterization of brain and sex hormone levels in a racially diverse sample of middle-age women.

女性比男性更有可能发展阿尔茨海默氏病（AD）和可用的研究 这不仅是因为他们的预期寿命比男性更长。这增加了 风险可能部分原因是在整个生命周期中都会波动性激素。性激素可能 对AD脑生物标志物（Aβ和TAU水平）以及通过 炎症，睡眠中断以及脑血流和体积减少，所有这些都是 广告的独立风险因素。非裔美国人 - 男人和妇女 - 也有所增加 与高加索人相比的风险。因此，机械研究和干预措施必须是 在非洲裔美国人和高加索人的参与者中进行了彻底检查和测试。 拟议项目的目的是确定大脑与全身性别之间的关系 对广告风险最大的个体中已知的AD生物标志物的骑马。 150中年，非洲 美国（n = 75）和高加索人（n = 75）妇女将被录取为期两年 学习。主要目的是测试大脑和血清性激素是否（雌二醇， 雌酮，孕激素，睾丸激素）差异影响AD风险因素（炎症，睡眠 ）和脑血流，），如果性骑士水平适应这些之间的关系 危险因素和AD生物标志物（认知，CSF，神经形象）。我们将利用现有的NIH 资助，表征良好的队列（n = 291;随后是MPIS Wharton＆Hu），包括中间 AD的高风险女性（通过家族史或APOE E4等位基因） 基线和纵向血液，CSF和MRI分析至少2年。我们还将测试我们的 基于我们广泛的曲目，在一个为非洲裔美国人提供丰富的独特队列中的假设 潜水队队列中招募和分析衰老和AD生物标志物的记录。参与者会 每年完成3次研究访问。每年，我们都会收集医疗和药物史， 主观睡眠，认知测试和问卷（压力，睡眠，运动，营养） 参与者还可以接受性激素和炎症标记的血液吸血。基线 和第二年，参与者将遵守大约协议，并参与：腰 脊柱液体收集，神经影像学的穿刺，将带回家无创的监测器 收集客观睡眠数据要磨损1晚。我们已经组装了一个多学科 团队具有性激素和衰老，广告生物标志物，炎症， 神经影像学，睡眠和生物统计学。数据告知大型NIH资助的研究，并向我们 知识，提供最大，最全面，最全面的生物标志物驱动的特征 大致多样化的中年妇女样本中的大脑和性激素水平。