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

女性比男性更容易患阿尔茨海默病（AD），现有的研究表明， 这不仅是因为女性的预期寿命比男性长。这种增加的 风险可能部分是由于性激素在整个生命周期中的波动。可能是性激素 对AD脑生物标志物（A β和tau水平）有直接作用，以及通过 炎症，睡眠中断，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-也在增加 与高加索人相比，AD的风险。因此，机械研究和干预措施需要 在非裔美国人和白人参与者中进行了彻底的检查和测试。的 该项目的目的是确定大脑和系统性别之间的关系 激素对已知的AD生物标志物的作用。150名中年非洲人 美国（n = 75）和高加索（n = 75）女性将入组这项为期2年的观察性研究 study.主要目的是测试脑和血清性激素（雌二醇， 雌酮、孕酮、睾酮）对AD危险因素（炎症、睡眠）的影响差异显著 和脑血流量，），如果性激素水平调节这些之间的关系， 风险因素和AD生物标志物（认知、CSF、神经成像）。我们将利用现有的NIH 资助，特征良好的队列（n = 291;其次是MPI沃顿商学院和胡），包括中等- AD高危年龄女性（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 基于我们的广泛跟踪， 在招募和分析不同队列中的衰老和AD生物标志物方面的记录。参与者将 每年完成3次研究访视。每年，我们将收集病史和用药史， 主观睡眠、认知测试和问卷调查（压力、睡眠、锻炼、营养） 参与者还接受性激素和炎症标记物的抽血。基线时 和第2年，参与者将接受上述方案，并参加：腰椎 穿刺收集脊髓液，神经成像，并将带回家的非侵入性监测， 收集客观睡眠数据，佩戴1晚。我们组织了一个多学科的 在性激素和衰老、AD生物标志物、炎症 神经成像睡眠和生物统计学数据为NIH资助的大型研究提供了信息， 知识，提供最大和最全面的，生物标志物驱动的，表征 大脑和性激素水平在不同种族的中年妇女样本。

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.