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

项目总结/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）海马体（内侧颞叶内的关键大脑结构）受损; (3)年龄是AD和COVID-19严重发病率和死亡率的风险因素。因此，更清晰 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 这为未来的研究提供了信息，即免疫系统中与年龄相关的衰退和功能障碍如何发挥作用， 在阿尔茨海默病的病因和病理学中的因果作用。 此外，老年非裔美国人的死亡率或严重健康状况异常高， 如果他们暴露于SARS-CoV-2病毒-COVID-19的病原体，后果将不堪设想。 行为和生活方式因素-包括低水平的体力活动，心血管健康状况差，高利率 肥胖和压力水平升高-可能是导致COVID-19死亡率增加的原因， 老年非裔美国人，尽管他们被普遍认为是高失业率的潜在贡献者， AD在非裔美国人中。 这份为期一年的行政补充文件旨在了解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）是在人们的免疫健康的变化 感染SARS-CoV-2的人，其行为和神经风险标志物增加， AD，以及未来转化为遗忘型轻度认知障碍（aMCI）的长期高风险， AD. (2)COVID-19，包括轻度或无症状感染，是否会导致神经系统的持久功能中断 内侧颞叶和海马内的网络，如果是这样，这些与可测量的 认知缺陷(3)为什么一些年长的非洲裔美国人遭受的COVID-19后果远比 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后果是什么。 有了这笔补充资金，我们将扩大父母补助金的方法，从（a）100名 我们过去的参与者计划在2020-2021年返回他们的2年或4年随访访问， 现有的父母资助方案，加上（B）100名有SARS-CoV-2感染史的新个体。所有 参与者将接受完整的当前R 01方案（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。初步的横断面分析 (Aims 1和2）将评估（1）既往SARS-CoV-2感染是否与认知和神经功能相关 网络功能障碍，特别是与内侧颞叶有关，类似于我们在那些 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有关，特别是CD 8 + T细胞衰老。这将导致 纵向分析（目标3）评估老年非裔美国人的SARS-CoV-2感染是否 与认知能力下降和转化为aMCI或AD的比率较高相关。

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.