Risk Factors for Future Cognitive Decline and Alzheimers Disease in Older African Americans

项目摘要 与白色美国人相比，非裔美国人的阿尔茨海默病（AD）患病率是其两倍。 我们对这种健康差距的原因还不太了解。特别是，继续有一个 缺乏关于老年非裔美国人一生中认知和神经变化的数据 以及这些与AD的健康和生活方式、环境和遗传风险因素的关系。于本 格兰特周期，我们已经表明，低水平的有氧健身和睡眠质量差可能是关键的驱动因素， 认知能力下降和老年非裔美国人的AD。然而，这些可能改变的影响 健康和生活方式变量在所有个体中并不一致：相反，遗传变异和社会 环境因素以复杂的方式相互作用，以调节有氧健身和睡眠质量的影响 大脑健康为了进一步调查这些知识差距，我们将利用我们16年的跟踪记录 （2006-2022年）通过与教会、老年中心、 医疗诊所，公共住房和其他组织，服务于大纽瓦克，新泽西州地区， 帮助我们成功招募了年长的非裔美国人具体来说，我们将招募240名认知 年龄在60岁及以上的健康受试者，并在第3年和第4年对他们进行重新测试，以进行第二周期（两年）随访。 所有年龄在80岁或以上的参与者将每年进行一次测试，因为在一年内下降的可能性更大。 年表现出认知能力下降的初步迹象的参与者-但不足以被归类为轻度 认知障碍（MCI）或AD也将每年进行一次测试。尽管我们的研究对象中有近10%的人 从2019冠状病毒病，我们仍然计划结转290名参与者从我们目前的R 01和以前的R56， 周期III（四年）、周期IV（六年）和/或周期V（八年）评估。因此，模损耗，我们 在这项研究中，我计划了一个530人的净队列，代表了一个老年非洲人的队列， 美国人除了我们之前的认知，健康，生活方式，遗传和MRI评估外，我们现在还包括 扩大对健康的社会决定因素（SDOH）的关注，并增加两个基于血液的 AD神经病理学的生物标志物：42至40个氨基酸长的淀粉样蛋白β的比例，斑块的标志物 病理学和磷酸化tau，AD相关tau磷酸化和分泌的标志物。我们现有 社区参与和研究基础设施将实现以下四个新的具体目标：（1） 检查有氧健身和睡眠质量是否与遗传变异相互作用以影响认知能力 老年非裔美国人的表现，神经功能和神经病理学;（2）扩大方法， 通过评估一种新的邻域劣势度量的预测值来研究SDOH， 基于与废弃建筑物的空间接近度;（3）评估我们的新认知和神经标记， 前驱AD的措施;和（4）确定有氧健身和睡眠质量如何与遗传相互作用， 预测认知和AD神经病理学的纵向变化以及向MCI或AD的转化。

PROJECT SUMMARY African Americans have double the prevalence of Alzheimer’s disease (AD) as compared to white Americans. We do not sufficiently understand the causes of this health disparity. In particular, there continues to be a dearth of data on the cognitive and neural changes that occur across the lifespan in older African Americans and how these relate to health and lifestyle, environmental, and genetic risk factors for AD. During the current grant cycle, we have shown that low levels of aerobic fitness and poor sleep quality may be key drivers of cognitive decline and AD in older African Americans. However, the impact of these potentially-modifiable health and lifestyle variables are not uniform across all individuals: rather, genetic variations and socio- environmental factors interact in complex ways to moderate how aerobic fitness and sleep quality influence brain health. To investigate these knowledge gaps further, we will leverage our track record of sixteen years (2006-2022) of deep community engagement through innovative partnerships with churches, senior centers, medical clinics, public housing and other organizations that serve the greater Newark, NJ area that has contributed to our success in enrolling older African Americans. Specifically, we will recruit 240 cognitively healthy participants ages 60 and above, and retest them in years 3 and 4 for their Cycle II (two-year) follow up. All participants who are age 80 or above will be tested every year, due to higher likelihood of decline within one year. Participants who show preliminary signs of cognitive decline—but not sufficient to be classified as mild cognitive impairment (MCI) or AD—will also be tested annually. Despite the deaths of almost 10% of our cohort from Covid-19, we still project carrying forward 290 participants from our current R01 and previous R56 for Cycle III (four-year), Cycle IV (six-year) and/or Cycle V (8-year) assessments. Thus, modulo attrition, we project a net cohort of 530 people for this study representing a longitudinally-followed cohort of older African Americans. In addition to our prior cognitive, health, lifestyle, genetic, and MRI assessments, we now include an expanded focus on Social Determinants of Health (SDOH) as well as the addition of two blood-based biomarkers for AD neuropathology: the ratio of 42 to 40 amino acid-long amyloid β, a marker of plaque pathology, and phosphorylated tau, a marker of AD-related tau phosphorylation and secretion. Our existing community engagement and research infrastructure will enable the following four new Specific Aims: (1) Examine whether aerobic fitness and sleep quality interact with genetic variations to influence cognitive performance, neural function, and neuropathology in older African Americans; (2) Expand methodologies for studying SDOH by assessing the predictive value of a novel measure of neighborhood disadvantage that is based on spatial proximity to abandoned buildings; (3) Evaluate our novel cognitive and neural markers as measures of prodromal AD; and (4) Determine how aerobic fitness and sleep quality interact with genetics to predict longitudinal changes in cognition and AD neuropathology as well as conversion to MCI or AD.