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: 10240604
• 负责人: William Tzu-lung Hu
• 金额: $ 73.2万
• 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/10240604
• 关键词: Affect; African American; 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.

女性比男性更容易患阿尔茨海默病 (AD)，现有研究 表明这不仅是因为她们的预期寿命比男性更长。这增加了 风险可能部分归因于一生中性激素的波动。性激素可能 对 AD 大脑生物标志物（Aβ 和 tau 水平）有直接作用，以及通过 炎症、睡眠中断以及脑血流量和容量减少，所有这些都是 AD 的独立危险因素。非裔美国人（男性和女性）的比例也有所增加 与白种人相比，AD 的风险更高。因此，需要进行机制研究和干预措施 对非裔美国人和白人参与者进行了彻底的检查和测试。这 该项目的目的是确定大脑与系统性别之间的关系 AD 风险最高的个体中已知 AD 生物标志物上的激素。 150 中年，非洲人 美国 (n=75) 和白人 (n=75) 女性将参加这项为期两年的观察性研究 学习。主要目的是测试大脑和血清中的性激素（雌二醇、 雌酮、孕酮、睾酮）对 AD 危险因素（炎症、睡眠 和脑血流量，），以及性激素水平是否调节这些之间的关系 危险因素和 AD 生物标志物（认知、脑脊液、神经影像）。我们将利用现有的 NIH 资助的、特征明确的队列（n=291；其次是 MPI Wharton & Hu），包括中层 患有 AD 高危年龄的女性（通过家族史或 APOE e4 等位基因）已经患有 AD 至少 2 年的基线和纵向血液、脑脊液和 MRI 分析。我们还将测试我们的 基于我们广泛的追踪，丰富了非裔美国人的独特队列中的假设 在不同群体中招募和分析衰老和 AD 生物标志物方面创下了记录。参与者将 每年完成 3 次考察访问。每年，我们都会收集医疗和用药史， 主观睡眠、认知测试和问卷（压力、睡眠、运动、营养） 参与者还接受性激素和炎症标记物的抽血。在基线 第 2 年，参与者将接受上述协议，并参加：腰椎 穿刺用于收集脊髓液、进行神经成像，并将带回家一台无创监测仪 收集佩戴一晚的客观睡眠数据。我们汇集了多学科 团队在性激素和衰老、AD 生物标志物、炎症、 神经影像学、睡眠和生物统计学。数据为 NIH 资助的大型研究提供信息，并且，我们 知识，提供最大、最全面、生物标记驱动的表征 不同种族的中年女性样本的大脑和性激素水平。