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: 9898203
• 负责人: MARK A GLUCK
• 金额: $ 66.5万
• 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 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9898203
• 关键词: Address; Affect; African American; 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; 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.

尽管非裔美国人与年龄相关的认知能力下降和记忆丧失的风险较高—— 与美国白人相比，阿尔茨海默病 (AD) 的患病率是白人的两倍——我们没有充分了解 了解这种健康差异的原因，也不知道如何最好地集中未来的干预措施来补救 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 认知能力下降和AD；他们在非裔美国人中广泛存在，特别是在低收入群体中 社会经济社区表明，其中部分或全部可能是痴呆症高发病率的关键， 非裔美国人中的阿尔茨海默氏症。然而，人们对相对重要性（和相互作用）知之甚少。 非洲裔美国人 AD 的这些不同危险因素。此外，目前还缺乏相关数据 老年非裔美国人一生中发生的神经变化，尤其是那些患病风险最高的人 AD——以及这些与 AD 的行为和生活方式风险因素有何关系。 修订后的 R01 重新提交 — 包括来自我们 R56 桥梁奖项的四个月的试点数据和 标题为“非洲老年人未来认知能力下降和阿尔茨海默病的风险因素” 美国人”——将解决上述在理解阿尔茨海默病中少数族裔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学、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 在当前 R56 资助期间招募了 120 名遗留参与者。一半 (180) 将接受 MRI 脑部成像， 解决老年非裔美国人可用神经影像数据缺乏的问题。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，我们通过十年的计划解决非洲裔美国人研究参与和保留的障碍 与大纽瓦克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分校的非裔美国人大脑健康倡议：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，涉及社区外展、教育、 和参与度，以增强我们的研究招募和保留。其中许多努力都是通过以下方式资助的： 新泽西州卫生部少数民族和多元文化健康办公室向 PI 提供为期五年的资助。 其次，我们解决了评估和验证新颖的认知评估的需要，这些评估是 通过让所有参与者完成对前驱阿尔茨海默病的最早阶段的敏感 罗格斯大学泛化任务，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和 海马体，大脑区域在 AD 前驱期的最早阶段受到破坏。由于这些任务是基于 非语言动物条件反射范式，它们对于跟踪认知变化可能特别有价值 我们的人口受到教育水平低或语言不流利的影响。我们假设赤字 泛化能力——将之前学到的规则应用于新的任务要求和新的刺激的能力——将 与 AD 前驱期的认知衰退和神经变化相关并进行纵向预测。 目标#1。跨部门行为分析：我们将评估（1）健康状况的变化， 体能和活动与认知功能相关，以及（2）这些因素的影响如何 变量通过教育、社会支持和遗传学调节，调节认知能力下降的风险 和老年非裔美国人的AD。！预测：体力活动和心血管健康水平较低 和高体重，将与罗格斯泛化任务的较差表现相关。 目标#2。神经机制分析：使用多模态 MRI 捕获大脑结构、功能和 白质完整性，我们评估目标#1中的关系如何由神经机制介导。 预测：泛化表现较差（体力活动和健身水平较低） 与海马体积、内嗅皮质厚度、海马内和 EC- 减少有关 海马连接性，海马和 EC 的 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 中描述，以及未来认知能力下降和进展为 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（为我们提供来自三个 传统 R56 队列的时间点和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障碍 标准化记忆评估缺陷之前的任务（与神经退行性变相关），以及 更有可能有体力活动较少和心血管健康状况较差的病史。 拟议的 R01 以我们正在进行的 R56 数据收集为基础，将克服当前的限制 了解老年非裔美国人认知能力下降和 AD 的高发生率，同时提供进一步的信息 创新认知评估的临床和神经影像验证、罗格斯泛化任务、 这可能有助于检测和测量早期 AD 前驱期的认知变化。