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

老年非裔美国人未来认知能力下降和阿尔茨海默病的危险因素

• 批准号: 10603215
• 负责人: MARK A GLUCK
• 金额: $ 4.31万
• 依托单位: RUTGERS THE STATE UNIV OF NJ NEWARK
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-15 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10603215
• 关键词: Address; Affect; African American; African American population; Age; Age-associated memory impairment; Alzheimer' s Disease; Alzheimer' s disease risk; Animals; Behavioral; Brain; Brain imaging; Brain region; Clinical; Cognitive; Communities; Community Outreach; Cultural Diversity; Data; Data Collection; Dementia; Education; Educational Background; Elderly; Funding; Future; Genetic; Grant; Health; Hippocampus (Brain); Howard Temin Award; Impaired cognition; Impairment; Intervention; Life Style; Longevity; Magnetic Resonance Imaging; Measures; Mediating; Memory; Memory Loss; Minority; Modeling; Nerve Degeneration; Neuropsychology; Participant; Patient Recruitments; Performance; Physical Fitness; Physical activity; Population; Prevalence; Process; Recording of previous events; Research; Risk; Risk Factors; Sampling; Sleep Deprivation; Social support; Standardization; Stimulus; Stress; Structure; Testing; Thick; Time; Trust; Universities; Validation; Variant; base; behavior influence; brain health; cardiovascular fitness; caucasian American; cognitive change; cognitive function; cognitive testing; cohort; community partnership; conditioning; depressive symptoms; entorhinal cortex; fitness; health disparity; high risk; innovation; lifestyle factors; minority health disparity; multimodality; neuroimaging; neuromechanism; novel; prodromal Alzheimer' s disease; programs; recruit; relating to nervous system; resilience; sedentary lifestyle; socioeconomics; success; white matter

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.

尽管非洲裔美国人的认知能力下降和记忆力丧失的风险较高，但 与白人美国人相比，阿尔茨海默氏病（AD）的患病率是两倍 了解这种健康差异的原因，也不了解如何最好地集中于未来的介入努力来补救 年龄较大的非裔美国人的健康危机。压力，睡眠不足，久坐的生活方式，差 心血管健身，抑郁症状，高体重和低教育都是已知的风险因素 认知能力下降和广告；他们在非洲裔美国人中的宽度范围，尤其是在低处 社会经济社区表明，其中的某些或全部可能是痴呆率高和 阿尔茨海默氏症中的非洲裔美国人。但是，关于相对重要性（和相互作用）知之甚少 在非裔美国人中广告的这些不同的风险因素中。此外，关于数据的数据死亡 在非裔美国人中，整个生命周期发生的神经变化 - 尤其是那些有最高风险的神经 AD-以及这些与AD的行为和生活方式风险因素如何相关。 此修订了R01重新提交 - 包括我们R56桥奖中的四个月的试点数据， 重新定位的“未来认知能力下降和阿尔茨海默氏病的危险因素 美国人” - 将解决理解阿尔茨海默氏症少数族裔健康差异的理由差距 疾病。我们将在65-85岁的360名非裔美国人中测试一系列神经心理学，认知，健康， 健身，遗传和生活方式评估。我们的样本包括240名新招聘的参与者以及 在当前R56赠款期间招募了120名传统参与者。一半（180）将使用MRI接收大脑成像， 解决了对年长的非裔美国人的可用神经影像学数据的匮乏。我们计划的两个方面 特别是创新的，对项目成功的重要意义。 首先，我们通过我们的十年来解决非裔美国人研究参与和保留的障碍 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计划：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，并涉及全年的社区外展，教育， 和参与，可以增强我们的研究招聘和保留。这些努力中的许多是通过 新泽西州卫生部少数民族和多元文化健康办公室向PI提供了五年的赠款。 其次，我们解决了评估和验证新的认知评估的需求 通过让所有参与者完成 Rutgers的概括任务，由Co-I（Myers）和Pi进行的创新认知评估 （Gluck）。这些任务源自Intorhinal Cortex（EC）和 海马，大脑区域在前驱AD的最早阶段中断。因为这些任务是基于 非语言动物调节范例，它们可能对于跟踪认知变化特别有价值 我们的人口受教育程度低或口头流利程度的影响。我们假设定义 概括（将先前学到的规则应用于新任务要求和新刺激的能力）将会 与前驱AD的认知下降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，（2）这些影响 变量是由教育，社会支持和遗传学介导的，以调节认知能力下降的风险 和年龄较大的非裔美国人的广告。！预测：体育锻炼和心血管健康水平较低 高体质量将与Rutgers概括任务的性能较差有关。 目标＃2。神经机制分析：使用多模式MRI捕获大脑结构，功能和 白质完整性，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：概括性能较差（体育锻炼和健身水平较低）将是 与海马体积减小，内嗅皮质厚度，海马内和EC-相关 海马连通性，并增加了海马和EC中的FA和MD。 目标＃3。纵向预测分析：确定关系的纵向方面 在AIM＃1和AIM＃2中描述，以及未来认知能力下降和向AMCI发展的预测指标 和广告，我们将在基线和此后每两年测试所有参与者（提供三个参与者 传统R56队列的时间点，以及新招募的参与者的两个时间点）。 预测：发展为AMCI或AD的参与者将在概括方面表现出早期损害 在标准化内存评估中定义之前，任务（与神经变性相关）以及 更有可能具有较低的体育锻炼病史和较差的心血管健身。 拟议的R01建立在我们正在进行的R56数据收集的基础上，将克服当前的局限 了解非洲裔美国人的认知能力下降和广告的高率，同时提供进一步 创新认知评估的临床和神经成像验证，鲁情的概括任务， 这可能证明可用于检测和测量早期前驱AD的认知变化。