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

尽管非裔美国人患与年龄相关的认知能力下降和记忆力丧失的风险较高， 与白色美国人相比，老年痴呆症（AD）的患病率是美国人的两倍-我们不充分 了解这种健康差距的原因，也不知道如何最好地集中未来的干预努力，以补救 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，高体重和低教育都是已知的危险因素， 认知能力下降和AD;它们在非裔美国人中的广泛存在，特别是在低收入人群中， 社会经济社区，表明其中一些或全部可能是痴呆症高发病率的关键， 非裔美国人中的老年痴呆症然而，关于其相对重要性（和相互作用） 在这些不同的风险因素中，此外，缺乏关于 在老年非裔美国人的一生中发生的神经变化-特别是那些风险最高的人， AD-以及这些与AD的行为和生活方式风险因素的关系。 这一修订后的R 01重新提交-包括四个月的试点数据，从我们的R56桥梁奖， 标题为“非洲老年人未来认知能力下降和阿尔茨海默病的危险因素 美国人”-将解决上述差距，了解少数民族的健康差距，在阿尔茨海默氏症 疾病我们将对360名年龄在65-85岁之间的非洲裔美国人进行神经心理、认知、健康、 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赠款期间招募了120名遗留参与者。其中一半（180人）将接受MRI脑成像， 解决了老年非裔美国人可用神经影像学数据的缺乏问题。我们计划的两个方面 对项目的成功具有特别的创新性和重要意义。 首先，我们通过我们的十年计划解决非洲裔美国人参与和保留研究的障碍。 与大纽瓦克的非洲裔美国人社区建立伙伴关系、合作和信任的历史 通过罗格斯大学纽瓦克分校的非裔美国人脑健康倡议：一个大学社区 伙伴关系（www.brainhealth.rutgers.edu）。我们与社区组织的长期合作关系 对我们过去的成功至关重要，并涉及全年的社区外展，教育， 和参与，以加强我们的研究招聘和保留。其中许多工作的资金来自 新泽西州卫生部少数民族和多元文化卫生办公室向PI提供五年赠款。 其次，我们解决了评估和验证新的认知评估的需要， 通过让所有参与者完成 罗格斯概括任务，由Co-I（Myers）和PI开发的创新认知评估 （格鲁克）。这些任务源自内嗅皮层（EC）的先前神经计算模型， 海马，在前驱AD的最早阶段被破坏的脑区域。由于这些任务是基于 非言语动物条件反射范式，它们可能是特别有价值的跟踪认知变化， 我们的人口受教育程度低或语言流利程度低的影响。我们假设， 概括能力--将先前学到的规则应用于新任务需求和新刺激的能力--意志 与前驱AD的认知下降和神经变化相关，并可纵向预测。 目标1。横断面行为分析：我们将评估（1）健康状况的变化， 身体健康和活动与认知功能相关，以及（2）这些因素的影响如何 在调节认知能力下降的风险中，受教育程度、社会支持和遗传因素的影响 老年非裔美国人的AD！预测：低水平的身体活动和心血管健康 和高体重，将与罗格斯大学概括任务的表现较差。 目标2。神经机制分析：使用多模态MRI捕捉大脑结构、功能和 白色物质的完整性，我们评估目标#1中的关系是如何通过神经机制介导的。 预测：可能的泛化性能（以及低水平的身体活动和健身）将 与海马体积、内嗅皮质厚度、海马内和EC- 海马连接，海马和EC中FA减少，MD增加。 目标3。纵向预测分析：确定关系的纵向方面 目标#1和目标#2中所述，以及未来认知下降和进展为aMCI的预测因素，沿着 和AD，我们将在基线和此后每两年对所有参与者进行一次测试（为我们提供三个月的数据）。 传统R56组的两个时间点，以及新招募的参与者的两个时间点）。 预测：进展为aMCI或AD的参与者将在泛化方面表现出早期损伤 任务（与神经退行性变相关）之前，在标准化的记忆评估赤字，以及 更有可能有较低的身体活动和较差的心血管健康的历史。 拟议的R 01建立在我们正在进行的R56数据收集的基础上，将克服目前的局限性， 了解老年非裔美国人认知能力下降和AD的高发病率，同时提供进一步的 创新认知评估的临床和神经影像学验证，罗格斯概括任务， 这可能被证明对检测和测量早期前驱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.