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

项目摘要 阿尔茨海默病和相关痴呆症是一个主要的公共卫生负担， 非裔美国人这种差异背后的机制尚不清楚，但升高的血液 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， 和高血压的严重程度。因此，年龄较大的非裔美国人往往有更大的累积接触 在整个成年期血压升高的风险比年长的白人高。然而，没有先前的研究量化了 高血压对阿尔茨海默病和相关痴呆的种族差异的贡献。有 解决这一重要问题的重大方法挑战，包括：（1） 从高血压发病年龄到成年晚期累积暴露于高血压， (2)在不同人群中测量认知功能，以及（3）可能的生存偏差，这可能会 对非裔美国人的影响有差异。本研究计划的科学目标是确定 从成年中期到成年晚期血压升高介导了阿尔茨海默氏症的种族差异 疾病和相关的痴呆症。本项目采用创新的方法来研究这一重要问题 现有数据来自两个不同的北方加州队列：加州大学戴维斯分校老龄化 多样性队列和凯撒永久北方加州多相健康检查队列， 将成年中期的身体检查与长期的医疗记录信息联系起来。分析将解决 通过检查累积暴露于升高的血液中， 在成年期的多个点测量压力，开发一种新的基于神经成像的大脑健康 指数在不同的人群，并量化的生存偏倚的潜在程度，使用综合 中年数据来解释生存差异。该研究计划由培训计划补充， 基于申请人在流行病学和生物统计学方面的背景，并包括以下方面的新培训（1） 测量和建模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症，（3）通过神经成像评估大脑健康，和（4）生物学 与阿尔茨海默氏症和相关痴呆症有关的血管疾病。联合研究和 培训计划将为申请人成功的独立研究生涯做好准备，重点是确定 不同人群中阿尔茨海默病和相关痴呆症的可变决定因素。的 本项目所涉及的方法学挑战是许多关于性别差异研究领域的共同问题， 老年痴呆症和相关疾病的整个生命过程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.