Risk Factors for Future Cognitive Decline and Alzheimer's Disease in Older African Americans

尽管非裔美国人患上与年龄相关的认知衰退和记忆力丧失的风险很高- 与美国白人相比，阿尔茨海默病(AD)的患病率是白人的两倍--我们还不够 了解这种健康差距的原因，也不了解如何最好地集中未来的干预努力来补救 这场老年非裔美国人的健康危机。压力、睡眠不足、久坐不动的生活方式、贫穷 心血管健康、抑郁症状、高体重和低教育程度都是已知的危险因素 认知衰退和阿尔茨海默病；他们在非裔美国人中广泛存在，特别是在Low 社会经济社区的研究表明，这些因素中的一些或全部可能是痴呆症高发病率和 非裔美国人中的阿尔茨海默病。然而，人们对它们的相对重要性(以及相互作用)知之甚少 在这些非裔美国人患AD的不同风险因素中。此外，数据还很匮乏 老年非裔美国人一生中发生的神经变化--特别是那些患糖尿病风险最高的人 AD--以及这些因素与AD的行为和生活方式风险因素之间的关系。 此修订后的R01重新提交-包括来自我们的R56桥梁奖励的四个月试点数据和 更名为《老年非洲人未来认知能力下降和阿尔茨海默病的风险因素》 美国人“-将解决上述在了解阿尔茨海默氏症少数群体健康差异方面的差距 疾病。我们将对360名年龄在65-85岁的非裔美国人进行一系列神经心理、认知、健康等方面的测试， 健康、遗传和生活方式评估。我们的样本包括240名新招募的参与者以及 在目前的R56赠款中招募了120名遗留参与者。一半(180人)将接受使用磁共振成像的大脑成像， 解决缺乏关于老年非裔美国人的可用神经成像数据的问题。我们计划的两个方面 尤其具有创新性，对项目的成功具有重要意义。 首先，我们通过十年的研究，解决了非裔美国人参与和保留研究的障碍 与大纽瓦克的非裔美国人社区的伙伴关系、合作和信任的历史 通过罗格斯大学-纽瓦克的非裔美国人脑健康倡议：大学-社区 合作伙伴关系(www.brainHealth.rutgers.edu)。我们与社区组织的长期关系 对我们过去的成功至关重要，并涉及社区外展、教育、 和参与度，以支持我们的研究、招聘和留住。这些努力中的许多都是通过 新泽西州卫生部少数民族和多元文化健康办公室向PI提供的为期五年的赠款。 其次，我们解决了评估和验证新的认知评估的需要，这些评估是 通过让所有参与者完成先兆阿尔茨海默氏病的 罗格斯泛化任务，由Co-I(Myers)和PI开发的创新认知评估 (幸好)。这些任务是从先前的内嗅皮层(EC)和 海马体，大脑区域在前驱阿尔茨海默病的早期阶段被破坏。因为这些任务基于 非语言动物条件作用范式，它们可能对跟踪认知变化在 我们的人口受到低教育水平或语言流利性的影响。我们假设美国的财政赤字 泛化-将以前学到的规则应用于新的任务要求和新的刺激的能力-意志 与先兆阿尔茨海默病的认知衰退和神经变化相关，并纵向预测。 目标#1.横断面行为分析：我们将评估(1)健康的变化， 身体健康和活动与认知功能相关，以及(2)这些因素的影响 在调节认知衰退风险方面，变量受教育、社会支持和遗传因素的影响 老年非裔美国人中的AD。！预测：低水平的体育活动和心血管健康 和较高的体重，将与较差的罗格斯泛化任务的表现相关。 目的#2.神经机制分析：使用多模式磁共振成像来捕捉大脑结构、功能和 白质完整性，我们评估了目标1中的关系是如何由神经机制调节的。 预测：泛化性能较差(体力活动和健康水平较低)将是 与海马体体积、内嗅皮质厚度、海马区和EC- 海马区连通性降低，海马区和EC区FA减少，MD增加。 目标#3.纵向预测分析：确定关系的纵向方面 在目标#1和目标#2中描述的，以及未来认知能力下降和发展为aMCI的预测因素 和AD，我们将在基线和此后每两年测试所有参与者(向我们提供三年的数据 传统R56队列的时间点，以及新征聘参与者的两个时间点)。 预测：进展到aMCI或AD的参与者将在泛化方面表现出早期损害 标准化记忆评估缺陷之前的任务(与神经变性相关)以及 更有可能有较少的体力活动和较差的心血管健康史。 建议的R01以我们正在进行的R56数据收集为基础，将克服目前在以下方面的限制 了解老年非裔美国人认知功能减退和阿尔茨海默病的高比率，同时提供进一步的 创新认知评估的临床和神经成像验证，罗格斯泛化任务， 这可能被证明对检测和测量早期先兆AD的认知变化有用。

Although African Americans are at elevated risk for age-related cognitive decline and memory loss— with double the prevalence of Alzheimer's disease (AD) compared to white Americans—we do not sufficiently understand the causes of this health disparity, nor how to best focus future interventional efforts to remediate this health crisis among older African Americans. Stress, sleep deprivation, sedentary lifestyles, poor cardiovascular fitness, depressive symptoms, high body mass, and low education are all known risk factors for cognitive decline and AD; their widespread presence among African Americans, particularly in low socioeconomic communities, suggests that some or all of these may be key to the high rates of dementia and Alzheimer's among African Americans. However, little is known about the relative importance (and interactions) among these different risk factors for AD in African Americans. Additionally, there is a dearth of data on the neural changes that occur across the lifespan in older African Americans-- especially those at highest risk for AD-- and how these relate to behavioral and lifestyle risk factors for AD. This revised R01 resubmission—including four months of pilot data from our R56 bridge award and retitled “Risk Factors for Future Cognitive Decline and Alzheimer's Disease in Older African Americans”—will address the aforementioned gaps in understanding minority health disparities in Alzheimer's disease. We will test 360 African Americans, ages 65-85, on a battery of neuropsychological, cognitive, health, fitness, genetic, and lifestyle assessments. Our sample includes 240 newly recruited participants as well as 120 legacy participants recruited during the current R56 grant. Half (180) will receive brain imaging using MRI, addressing the paucity of available neuroimaging data on older African Americans. Two aspects of our plans are especially innovative and significant to project success. First, we address barriers to African-American research participation and retention through our ten-year history of partnership, cooperation, and trust with the African-American communities of Greater Newark through Rutgers University-Newark's African American Brain Health Initiative: A University-Community Partnership (www.brainhealth.rutgers.edu). Our long-term relationships with community-based organizations have been critical to our past successes and involve year-round programs for community outreach, education, and engagement that bolster our research recruitment and retention. Many of these efforts are funded through a five-year grant to the PI from the NJ Department of Health's Office of Minority and Multicultural Health. Second, we address the need for evaluating and validating novel cognitive assessments that are sensitive to the earliest stages of prodromal Alzheimer's disease by having all participants complete the Rutgers Generalization Tasks, innovative cognitive assessments developed by the Co-I (Myers) and PI (Gluck). These tasks are derived from prior neurocomputational models of the entorhinal cortex (EC) and hippocampus, brain regions disrupted in the earliest stages of prodromal AD. As these tasks are based on non-verbal animal conditioning paradigms, they may be especially valuable for tracking cognitive changes in our population, which is affected by low levels of education or verbal fluency. We hypothesize that deficits in generalization—the ability to apply previously learned rules to novel task demands and new stimuli—will correlate with, and longitudinally predict, cognitive decline and neural changes in prodromal AD. Aim #1. CROSS-SECTIONAL BEHAVIORAL ANALYSES: We will evaluate (1) how variations in health, physical fitness and activity are correlated with cognitive function, and (2) how the influence of these variables is mediated by education, social support, and genetics, in modulating the risk of cognitive decline and AD in elderly African Americans.!Predictions: Low levels of physical activity and cardiovascular fitness and high body mass, will be correlated with poorer performance on the Rutgers Generalization Tasks. Aim #2. NEURAL MECHANISM ANALYSES: Using multimodal MRI to capture brain structure, function, and white matter integrity, we evaluate how the relationships in Aim #1 are mediated by neural mechanisms. Predictions: Poorer generalization performance (and low levels of physical activity and fitness) will be associated with reduced hippocampal volume, entorhinal cortical thickness, intra-hippocampal and EC- hippocampal connectivity, and decreased FA and increased MD in the hippocampus and EC. Aim #3. LONGITUDINAL PREDICTIVE ANALYSES: To identify longitudinal aspects of the relationships described in Aim #1 and Aim #2, along with predictors of future cognitive decline and progression to aMCI and AD, we will test all participants at baseline and every two years thereafter (providing us data from three time-points for the legacy R56 cohort, and two time-points for the newly recruited participants). Predictions: Participants who progress to aMCI or AD will show early impairments on the generalization tasks (correlated with neurodegeneration) prior to deficits in standardized memory assessments, as well as being more likely to have a history of lower physical activity and poorer cardiovascular fitness. The proposed R01, building on our ongoing R56 data collection, will overcome current limitations to understanding the high rate of cognitive decline and AD in older African Americans, while providing further clinical and neuroimaging validation of innovative cognitive assessments, the Rutgers Generalization Tasks, which may prove useful for detecting and measuring cognitive changes in early prodromal AD.