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: 10017867
• 负责人: William Tzu-lung Hu
• 金额: $ 74.45万
• 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/10017867
• 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 environment; Hormonal; Hormones; Image; Individual; Inflammation; Inflammatory; Interleukin-7; 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; 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上阿尔茨海默病(AD)，而且现有的研究 这表明，这不仅仅是因为她们的预期寿命比男性长。这增加了 风险很可能部分归因于一生中性激素的波动。性激素可能 对AD脑生物标志物(Aβ和tau水平)有直接作用，也有间接作用 炎症，睡眠障碍，脑血流量和脑容量减少，所有这些都是 AD的独立危险因素。非洲裔美国人--男性和女性--也在增加 AD与高加索人之间的风险。因此，机械性研究和干预措施需要 在非裔美国人和高加索人参与者中进行了彻底的检查和测试。这个 这项拟议的项目的目的是确定大脑和全身性别之间的关系 AD高危人群中已知AD生物标志物上的激素。150名中年人，非洲人 美国女性(n=75)和高加索女性(n=75)将参加这次观察性活动，为期两年。 学习。主要目的是测试大脑和血清性激素(雌二醇， 雌酮、孕酮、睾酮)对AD危险因素(炎症、睡眠)有不同的影响 和脑血流量)，如果性激素水平缓和了这些之间的关系 危险因素和AD生物标志物(认知、脑脊液、神经成像)。我们将利用现有的NIH 资助的、特征良好的队列(n=291；其次是MPI Wharton&Hu)，包括中级 已患AD的高危年龄妇女(通过家族病史或APOE e4等位基因) 至少2年的基线和纵向血液、脑脊液和核磁共振分析。我们还将测试我们的 基于我们广泛的跟踪，一个独特的队列中的假设丰富了非裔美国人 在招募和分析不同队列中的衰老和AD生物标记物方面有记录。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历史， 主观睡眠、认知测试和问卷调查(压力、睡眠、运动、营养) 参与者还会抽血检测性激素和炎症标志物。在基线上 和第二年，参与者将接受上述方案，并参与：腰椎 用于脊髓液采集，神经成像的穿刺术，并将带回家的无创监护仪 收集客观睡眠数据，佩戴1晚。我们已经组建了一个多学科的 在性激素和衰老、AD生物标记物、炎症、 神经成像、睡眠和生物统计学。数据为NIH资助的更大规模的研究提供信息，并为我们的 知识，提供最大和最全面的、生物标记物驱动的、表征 不同种族的中年女性样本中的大脑和性激素水平。