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

项目摘要/摘要 阿尔茨海默病(AD)和新冠肺炎有多个共同特征，包括(1)干扰 免疫系统；(2)海马体的破坏，海马体是内侧颞叶的关键大脑结构； (3)年龄是AD的危险因素，也是新冠肺炎严重发病率和死亡率的危险因素。因此，一个更清晰的 了解新冠肺炎如何影响认知、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，即与年龄相关的免疫系统衰退和功能障碍可能会对 阿尔茨海默病的病因和病理中的因果作用。 此外，年长的非裔美国人的死亡率极高或健康状况极差。 如果他们接触到SARS-CoV-2病毒--新冠肺炎的病原体--会造成严重后果。 行为和生活方式因素--包括低水平的体力活动、差的心血管健康、高发病率 肥胖和压力水平的增加-可能是导致一些人新冠肺炎死亡率上升的原因 年长的非裔美国人，就像他们通常被认为是高死亡率的潜在贡献者一样 非裔美国人的广告。 这份为期一年的行政补充资料旨在了解新冠肺炎和AD之间的联系 非裔美国人通过解决三个关键问题：(1)人们免疫健康的变化 感染SARS-CoV-2的人行为和神经风险标记物增加 AD，以及未来转变为遗忘性轻度认知障碍(AMCI)的长期较高风险 广告。(2)新冠肺炎，包括轻微或无症状的感染，是否会对神经造成持久的功能障碍？ 内侧颞叶和海马体内的网络，如果是，这些网络是否与可测量的 认知缺陷？(3)为什么一些年长的非裔美国人在新冠肺炎治疗中遭受的后果比 他们的同龄人，以及新冠肺炎对老年非裔美国人的长期大脑健康影响。 有了这笔补充拨款，我们将扩大父母捐赠的方法，从(A)100人中采集血液 我们过去的参与者计划在2020-2021年返回进行为期2年或4年的跟踪访问，作为 (B)100名有SARS-CoV-2感染病史的新患者。全 参与者将接受完整的当前R01方案(健康、健身、认知和可选大脑)的管理 成像)以及新的新冠肺炎和免疫学评估。初始横断面分析 (目标1和目标2)将评估(1)先前感染SARS-CoV-2是否与认知和神经有关 网络功能障碍，特别是与内侧颞叶有关，类似于我们在 处于阿尔茨海默病临床前阶段的高风险，以及(2)认知和神经损害的程度 与免疫系统功能失调有关，特别是CD8+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是否感染SARS-CoV-2 与较高的认知衰退率和转换为轻度认知障碍或阿尔茨海默病相关。

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.