Cognitive, Neural, and Immunological Consequences of COVID-19 in Older African Americans and How They Relate to Risk for Alzheimer’s Disease

COVID-19 对老年非裔美国人的认知、神经和免疫学影响及其与阿尔茨海默病风险的关系

• 批准号: 10267980
• 负责人: MARK A GLUCK
• 金额: $ 64.34万
• 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/10267980
• 关键词: Address; Administrative Supplement; African American; Age; Age-associated memory impairment; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease risk; Behavioral; Blood; Brain; Brain imaging; CD8-Positive T-Lymphocytes; COVID-19; COVID-19 mortality; Cell Aging; Cognition; Cognitive; Cognitive deficits; Cross-Sectional Studies; Death Rate; Etiology; Functional disorder; Funding; Future; Health; Health Alliance; Hippocampus (Brain); Immune system; Immunologics; Immunology; Impaired cognition; Impairment; Individual; Infection; Infectious Agent; Lead; Link; Measurable; Medial; Methods; Morbidity - disease rate; Neurophysiology - biologic function; Obesity; Outcome; Participant; Pathway interactions; Phase; Physical activity; Play; Protocols documentation; Recording of previous events; Risk; Risk Factors; Risk Marker; Role; SARS-CoV-2 exposure; SARS-CoV-2 infection; Schedule; Stress; Structure; Temporal Lobe; Time; Virus; Visit; age related; aging brain; amnestic mild cognitive impairment; brain health; cardiovascular fitness; caucasian American; clinically relevant; cohort; experience; fitness; follow-up; high risk; immune health; insight; lifestyle factors; longitudinal analysis; network dysfunction; neural network; parent grant; peer; pre-clinical; relating to nervous system

PROJECT SUMMARY/ABSTRACT Alzheimer's Disease (AD) and COVID-19 share multiple common features including (1) disruption to the immune system; (2) disruption to the hippocampus, a key brain structure within the medial temporal lobe; (3) age being a risk factor for both AD and severe morbidity and mortality from COVID-19. As such, a clearer understanding of how COVID-19 impacts cognition, neural function, and risk for AD may lead to new insights that inform future research on how age-related decline and dysfunction in the immune system may play a causal role in the etiology and pathology of Alzheimer's disease. Furthermore, Older African Americans have exceptionally high rates of death or severe health consequences if they are exposed to the SARS-CoV-2 virus—the causative infectious agent for COVID-19. Behavioral and lifestyle factors—including low levels of physical activity, poor cardiovascular fitness, high rates of obesity and elevated levels of stress—may be contributing to this increased COVID-19 mortality in some older African Americans, much as they are generally acknowledged to be potential contributors to high rates of AD in African Americans. This one year administrative supplement seeks to understand the links between COVID-19 and AD in African Americans by addressing three key questions: (1) Are changes in the immunological health of people who have been infected with SARS-CoV-2 associated with increases in behavioral and neural risk markers for AD, as well as longer-term higher risk for future conversion to amnestic mild cognitive impairment (aMCI) and AD. (2) Does COVID-19, including mild or asymptomatic infection, cause lasting functional disruption to neural networks within the medial temporal lobe and hippocampus, and, if so, are these associated with measurable cognitive deficits? (3) Why do some older African Americans suffer far worse outcomes from COVID-19 than their peers, and what are the long-term brain health consequences of COVID-19 for older African Americans. With this supplemental funding we will expand the parent grant methods to collect blood from (a) 100 of our past participants who are scheduled to return in 2020-2021 for their 2-year or 4-year follow up visits as part of the existing parent grant protocol, plus (b) 100 new individuals with a history of SARS-CoV-2 infection. All participants will be administered both the full current R01 protocol (health, fitness, cognitive, and optional brain imaging) as well as the new COVID-19 and immunology assessments. The initial cross-sectional analysis (Aims 1 and 2) will evaluate (1) whether a prior SARS-CoV-2 infection is associated with cognitive and neural network dysfunction, specifically related to the medial temporal lobe, similar to what we have seen in those at high risk of being in a preclinical phase of AD and, (2) the degree to which cognitive and neural impairments correlate with a dysfunctional immune system, specifically CD8+ T cell senescence. This will lead up to the longitudinal analysis (Aim 3) assessing whether or not SARS-CoV-2 infection in older African Americans is associated with a higher rate of cognitive decline and conversion to aMCI or AD.

项目概要/摘要 阿尔茨海默病 (AD) 和 COVID-19 有多个共同特征，包括 (1) 破坏 免疫系统；（2）破坏海马体，这是内侧颞叶内的关键大脑结构； (3) 年龄是 AD 以及 COVID-19 严重发病和死亡的危险因素。 了解 COVID-19 如何影响认知、神经功能和 AD 风险可能会带来新的见解 为未来的研究提供信息，了解与年龄相关的免疫系统衰退和功能障碍如何发挥作用 阿尔茨海默病的病因学和病理学中的因果作用。 此外，老年非裔美国人的死亡率或健康状况异常高 如果他们接触 SARS-CoV-2 病毒（COVID-19 的病原体），就会产生后果。 行为和生活方式因素——包括体力活动水平低、心血管健康状况不佳、比率高 肥胖和压力水平升高——可能是导致某些地区 COVID-19 死亡率增加的原因 老年非裔美国人，尽管人们普遍认为他们是导致高死亡率的潜在因素 AD 在非裔美国人中。 这一为期一年的行政补充旨在了解 COVID-19 和 AD 之间的联系 非裔美国人通过解决三个关键问题：（1）人们的免疫健康是否发生变化 感染 SARS-CoV-2 并与行为和神经风险标记增加相关的人 AD，以及未来转化为遗忘性轻度认知障碍 (aMCI) 的长期较高风险和 AD (2) COVID-19（包括轻度或无症状感染）是否会对神经系统造成持久的功能破坏 内侧颞叶和海马内的网络，如果是这样，这些网络是否与可测量的相关 (3) 为什么一些老年非裔美国人因 COVID-19 而遭受的后果要严重得多 他们的同龄人，以及 COVID-19 对老年非裔美国人的长期大脑健康影响是什么。 通过这笔补充资金，我们将扩大家长补助金的方法，以从 (a) 100 作为计划的一部分，我们过去的参与者计划在 2020-2021 年返回进行 2 年或 4 年的后续访问 现有家长资助协议的一部分，加上 (b) 100 名有 SARS-CoV-2 感染史的新个体。 参与者将接受完整的当前 R01 协议（健康、健身、认知和可选的大脑 成像）以及新的 COVID-19 和免疫学评估。 （目标 1 和 2）将评估 (1) 先前的 SARS-CoV-2 感染是否与认知和神经功能相关 网络功能障碍，特别与内侧颞叶相关，类似于我们在 处于 AD 临床前阶段的高风险，以及 (2) 认知和神经损伤的程度 与免疫系统功能失调相关，特别是 CD8+ T 细胞衰老。 纵向分析（目标 3）评估老年非裔美国人中的 SARS-CoV-2 感染是否是 与较高的认知能力下降和转化为 aMCI 或 AD 的比率相关。