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Risk Factors for Future Cognitive Decline and Alzheimers 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

基本信息

批准号：
10739344
负责人：
MARK A GLUCK
金额：
$ 153.92万
依托单位：
RUTGERS THE STATE UNIV OF NJ NEWARK
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-05-15 至 2028-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10739344
关键词：
Address Aerobic Exercise African American population Age Alzheimer&apos s Disease Alzheimer&apos s disease risk Alzheimer’s disease biomarker Amino Acids Amyloid beta-42 Amyloid beta-Protein Area Attention Award Behavior Biological Markers COVID-19 COVID-19 mortality Censuses Cessation of life Church Classification Clinic Clinical Trials Cognition Cognitive Communities Complex Data Elderly Enrollment Environmental Risk Factor Exercise Family Functional Magnetic Resonance Imaging Future Genetic Genetic Variation Glial Fibrillary Acidic Protein Goals Grant Health Health Disparities Research Health behavior Impaired cognition Individual Knowledge Learning Life Style Light Longevity Longitudinal Studies Magnetic Resonance Imaging Measures Medial Medical Medicine Memory Methodological Studies Neurophysiology - biologic function Neuropsychology Outcome Paper Participant Pathology Performance Persons Predictive Value Prevalence Productivity Protocols documentation Public Health Public Housing Publications Radial Research Research Infrastructure Risk Risk Factors Role Sex Differences Site Social Environment Stimulus Temporal Lobe Testing Variant apolipoprotein E-4 behavior influence blood-based biomarker brain health caucasian American cognitive change cognitive performance cohort community based participatory research community engagement deprivation fitness flexibility follow-up foot genetic risk factor health assessment health disparity high risk improvement on sleep indexing innovation insight lifestyle factors mild cognitive impairment neighborhood disadvantage neural neuromechanism neuropathology neuroprotection novel pandemic disease poor sleep primary outcome prodromal Alzheimer&apos s disease programs recruit research study risk variant secondary outcome sleep quality social health determinants socioenvironmental factor success tau-1 tool

项目摘要

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.

项目概要与美国白人相比，非洲裔美国人的阿尔茨海默病 (AD) 患病率是白人的两倍。我们还没有充分了解这种健康差异的原因。特别是，仍然存在缺乏有关老年非裔美国人一生中认知和神经变化的数据以及这些因素与 AD 的健康和生活方式、环境和遗传风险因素有何关系。当前期间在拨款周期中，我们已经证明，有氧健身水平低和睡眠质量差可能是导致老年非裔美国人的认知能力下降和 AD。然而，这些潜在可改变的影响所有个体的健康和生活方式变量并不统一：相反，遗传变异和社会变异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，我们将利用我们十六年的记录（2006-2022）通过与教堂、老年人中心的创新伙伴关系深入社区参与，为新泽西州纽瓦克地区提供服务的医疗诊所、公共住房和其他组织为我们成功招收老年非裔美国人做出了贡献。具体来说，我们将招募240名认知型年龄 60 岁及以上的健康参与者，并在第 3 年和第 4 年重新进行测试，以进行第二周期（两年）随访。所有 80 岁或以上的参与者每年都会接受测试，因为一年内衰退的可能性较大年。表现出认知能力下降初步迹象的参与者，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。尽管我们的队列中有近 10% 的人死亡从 Covid-19 起，我们仍计划将当前 R01 和之前 R56 中的 290 名参与者结转到第三周期（四年）、第四周期（六年）和/或第五周期（8 年）评估。因此，以损耗为模数，我们为这项研究规划了 530 人的净队列，代表纵向跟踪的非洲老年人队列美国人。除了我们之前的认知、健康、生活方式、遗传和 MRI 评估之外，我们现在还包括扩大对健康社会决定因素 (SDOH) 的关注，并增加了两种基于血液的因素 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 的比率，斑块的标志物病理学和磷酸化 tau 蛋白（AD 相关 tau 蛋白磷酸化和分泌的标志物）。我们现有的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老年非裔美国人的表现、神经功能和神经病理学； (2) 扩展方法论通过评估邻里劣势的新衡量标准的预测价值来研究 SDOH 基于与废弃建筑物的空间邻近性； (3) 将我们的新认知和神经标记评估为前驱 AD 的测量； (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。

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

High-Quality Sleep Mitigates ABCA7-Related Generalization Deficits in Healthy Older African Americans.

DOI：
10.3233/jad-230043
发表时间：
2023
期刊：
JOURNAL OF ALZHEIMERS DISEASE
影响因子：
4
作者：
Sinha, Neha;Fausto, Bernadette A.;Mander, Bryce;Gluck, Mark A.
通讯作者：
Gluck, Mark A.

Increased dynamic flexibility in the medial temporal lobe network following an exercise intervention mediates generalization of prior learning.

运动干预后，内侧颞叶网络中的动态灵活性提高了先前学习的概括。

DOI：
10.1016/j.nlm.2020.107340
发表时间：
2021-01
期刊：
Neurobiology of learning and memory
影响因子：
2.7
作者：
Sinha N;Berg CN;Yassa MA;Gluck MA
通讯作者：
Gluck MA

APOE ε4 status in healthy older African Americans is associated with deficits in pattern separation and hippocampal hyperactivation.

健康老年美国人的APOEε4状态与模式分离和海马过度激活的缺陷有关。

DOI：
10.1016/j.neurobiolaging.2018.05.023
发表时间：
2018-09
期刊：
Neurobiology of aging
影响因子：
4.2
作者：
Sinha N;Berg CN;Tustison NJ;Shaw A;Hill D;Yassa MA;Gluck MA
通讯作者：
Gluck MA

Cardio-Dance Exercise to Improve Cognition and Mood in Older African Americans: A Propensity-Matched Cohort Study.

有氧运动以改善非裔美国人的认知和情绪：一项倾向匹配的队列研究。

DOI：
10.1177/07334648211010580
发表时间：
2022-03
期刊：
Journal of applied gerontology : the official journal of the Southern Gerontological Society
影响因子：
0
作者：
Fausto BA;Azimipour S;Charles L;Yarborough C;Grullon K;Hokett E;Duberstein PR;Gluck MA
通讯作者：
Gluck MA

Examining the efficacy of a cardio-dance intervention on brain health and the moderating role of ABCA7 in older African Americans: a protocol for a randomized controlled trial.