Racial Disparities in Alzheimer's Disease and Related Dementias: The Role of Blood Pressure Throughout Adulthood

项目总结 阿尔茨海默病和相关痴呆症是一个主要的公共卫生负担，对 非裔美国人。这种差异背后的机制还不是很清楚，但血液升高。 压力可能是关键。与白人相比，非裔美国人的患病率更高，发病年龄更早， 以及更严重的高血压。因此，年长的非裔美国人往往有更大的累积风险敞口 与年长的白人相比，成年后血压升高的风险更大。然而，之前的研究还没有量化 高血压对阿尔茨海默病和相关痴呆的种族差异的贡献。确实有 解决这一重要问题的重大方法学挑战，包括(1)衡量 从高血压发病年龄到成年后期，累积暴露于高血压的风险， (2)不同人群认知功能的测量，以及(3)可能的生存偏见，这可能会 对非裔美国人有不同的影响。这项研究计划的科学目标是确定 在阿尔茨海默氏症患者中，从成年中期到成年后期的血压升高会导致种族差异 疾病和相关痴呆症。这个项目用一种创新的方法来研究这个重要的问题。 现有数据来自两个不同的北加州队列：加州大学戴维斯分校 多样性队列和凯撒永久北加州多相健康体检队列， 将中年体检与长期病历信息联系起来。分析将解决 通过检查累积暴露于升高的血液，上面概述了三个主要的方法学挑战 成年后在多个时间点测量的压力，发展了一种新的基于神经成像的大脑健康 在不同的人群中的指数，并量化潜在的生存偏向的大小 考虑差异存活率的中年数据。这项研究计划得到了一项培训计划的补充 以申请者在流行病学和生物统计学方面的背景为基础，并包括新的(1)培训 测量和模拟不同人群的认知功能，(2)临床评估和诊断 阿尔茨海默病和相关痴呆，(3)用神经成像评估大脑健康，和(4)生物学 与阿尔茨海默病和相关痴呆症相关的血管疾病。联合研究和 培训计划将使申请者为成功的独立研究生涯做好准备，专注于确定 不同人群中阿尔茨海默病和相关痴呆的可改变决定因素。这个 本项目中涉及的方法学挑战对于许多领域的差异研究是共同的 衰老与阿尔茨海默病及其相关疾病患者一生中对危险因素的累积暴露 痴呆症。

PROJECT SUMMARY Alzheimer’s disease and related dementias are a major public health burden and disproportionately affect African Americans. The mechanisms underlying this disparity are not well-understood, but elevated blood pressure could be key. Compared with whites, African Americans have higher prevalence, earlier age of onset, and greater severity of hypertension. Thus, older African Americans tend to have greater cumulative exposure to elevated blood pressure throughout adulthood than older whites. No prior research, however, has quantified the contribution of hypertension to racial disparities in Alzheimer’s disease and related dementias. There are significant methodological challenges to addressing this important question, including (1) measurement of cumulative exposure to elevated blood pressure from the age of onset of hypertension through late adulthood, (2) measurement of cognitive function in diverse populations, and (3) possible survival bias, which is likely to differentially affect African Americans. The scientific objective of this research plan is to identify the extent to which elevated blood pressure from mid- through late- adulthood mediates racial disparities in Alzheimer’s disease and related dementias. This project uses an innovative approach to examine this important question with existing data from two diverse Northern California cohorts: the University of California, Davis Aging Diversity Cohort and the Kaiser Permanente Northern California Multiphasic Health Checkup cohort, which links mid-adulthood physical examinations with long-term medical record information. Analyses will address the three major methodologic challenges outlined above by examining cumulative exposure to elevated blood pressure as measured at multiple points in adulthood, developing a novel neuroimaging-based brain health index in a diverse population, and quantifying the potential magnitude of survival bias using comprehensive midlife data to account for differential survival. This research plan is complemented by a training plan that builds on the applicant’s background in epidemiology and biostatistics and includes new training in (1) measuring and modeling cognitive function in diverse populations, (2) clinical assessment and diagnosis of Alzheimer’s disease and related dementias, (3) assessing brain health with neuroimaging, and (4) the biology of vascular disease relevant to Alzheimer’s disease and related dementias. The combined research and training plans will prepare the applicant for a successful independent research career focused on identifying modifiable determinants of Alzheimer’s disease and related dementias in diverse populations. The methodological challenges addressed in this project are common to many areas of research on disparities in aging and cumulative exposure to risk factors throughout the lifecourse for Alzheimer’s disease and related dementias.