The Impact of SARS-CoV-2 Infection and Vaccination on the Risk of Alzheimer’s Disease and Related Dementias

SARS-CoV-2 感染和疫苗接种对阿尔茨海默病和相关痴呆症风险的影响

• 批准号: 10729916
• 负责人: Jingxuan Wang
• 金额: $ 4.21万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-12-01 至 2025-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10729916
• 关键词: 2019-nCoV; Address; Affect; Aging; Alzheimer disease prevention; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Atherosclerosis; Biological; Biology; Blood Vessels; Brain; Brain region; COVID-19; COVID-19 diagnosis; COVID-19 impact; COVID-19 pandemic; COVID-19 survivors; COVID-19 vaccination; California; Caring; Central Nervous System; Clinical; Clinical Data; Clinical assessments; Cognition; Cognitive; Cognitive aging; Cohort Studies; Communicable Diseases; Data; Data Set; Dementia; Diagnosis; Disease; Early treatment; Elderly; Electronic Health Record; Emotional; Environment; Epidemiologic Methods; Foundations; Future; General Hospitals; Goals; Health Surveys; Health and Retirement Study; Healthcare; Hypoxia; Immune; Immune response; Impaired cognition; Individual; Infection; Inflammatory; Knowledge; Link; Long-Term Effects; Magnetic Resonance Imaging; Massachusetts; Mediating; Medicare claim; Memory; Mentorship; Methodology; Methods; Nerve Degeneration; Neurologic Deficit; Outcome; Parahippocampal Gyrus; Participant; Pathology; Persons; Phase; Postdoctoral Fellow; Prevalence; Prevention; Public Health; Recording of previous events; Research; Research Activity; Research Personnel; Resource Allocation; Risk; Risk Reduction; Role; SARS-CoV-2 B.1.617.2; SARS-CoV-2 infection; SARS-CoV-2 variant; San Francisco; Science; Shapes; Smell Perception; Statistical Methods; Structure; Survival Analysis; Symptoms; Thick; Time; Training; Training Activity; Universities; Vaccination; Variant; Viral; Virus; Work; aging population; biobank; brain health; brain magnetic resonance imaging; career; classification algorithm; clinical diagnosis; cognitive change; cohort; dementia risk; disorder risk; diverse data; electronic health data; endothelial dysfunction; epidemiology study; experience; high risk; improved; innovation; longitudinal dataset; machine learning method; multiple data sources; neuroimaging; neuroinflammation; novel; oxidative damage; pandemic disease; post SARS-CoV-2 infection; post-COVID-19; skills; white matter

PROJECT SUMMARY/ABSTRACT The growing prevalence of Alzheimer’s disease and Alzheimer’s related disorders (ADRD) is a critical public health concern, potentially exacerbated by the COVID-19 pandemic. Infectious diseases may increase ADRD risk by causing neuroinflammation and oxidative damage in the central nervous system, promoting atherosclerosis and endothelial dysfunction, or via other inflammatory, immune-response, and vascular mechanisms. Despite intriguing links between several infectious and neurodegenerative conditions, whether and how infectious diseases influence ADRD risk remains underexplored. This question is urgent especially during the COVID-19 pandemic, where the widespread SARS-CoV-2 infection has heavily impacted global public health. Mounting evidence suggests a significant fraction of those infected with SARS-CoV-2 may experience substantial and long-lasting sequelae, including cognitive decline and neurologic deficits. Many unknowns remain, including long-term outcomes and the role of COVID-19 vaccination and viral variants in modifying the effect of SARS-CoV-2 infection on cognitive decline and ADRD risk. This proposed F99/K00 project seeks to address these gaps with two specific aims using complementary longitudinal datasets and rigorous, advanced epidemiological and statistical methods. Aim 1 (F99 dissertation phase: 2023-2025) will use the previously identified COVID-19 brain magnetic resonance imaging (MRI) signature region to infer the long-term effects of infection on ADRD risk via brain structure changes. The COVID-19 MRI signature region comprises brain regions where cortical thickness and gray-white matter contrast was reduced after SARS- CoV-2 infection (identified in a longitudinal MRI study). The candidate will quantify the association between the COVID-19 MRI signature region and future ADRD risk among UK Biobank participants. Aim 2 (K00 postdoctoral phase: 2025-2029) will evaluate the effects of vaccination status and timing of SARS-CoV-2 infection on cognitive outcomes and ADRD among COVID-19 survivors. The candidate will use data from electronic health records (EHR) and a nationally representative cohort. Methodological innovations include the use of neuroimaging, causal survival analysis, machine learning methods for classification algorithms, as well as multiple data sources (i.e., clinical data from EHR and survey data from cohort studies). This proposal directly responds to the call to study the impact of COVID-19 on risk of ADRD and cognition from the National Alzheimer's Project Act (NAPA). The proposal extends the candidate’s quantitative expertise with advanced training in clinical and biological perspectives on ADRD as well as causal inference methods for aging research. Strong interdisciplinary mentorship teams and outstanding supportive training environments at the University of California, San Francisco (F99) and the Massachusetts General Hospital (K00) provide a foundation for the candidate to fill an important scientific gap on infectious disease and immune-related determinants of cognitive aging and ADRD, including infection with SARS-CoV-2.

项目摘要/摘要 阿尔茨海默氏病和阿尔茨海默氏症相关疾病（ADRD）的越来越普遍是关键的公众 健康关注，可能会因19日大流行而加剧。传染病可能会增加ADRD 通过在中枢神经系统中引起神经炎症和氧化损伤来风险，促进 动脉粥样硬化和内皮功能障碍，或通过其他炎症，免疫反应和血管 机制。尽管几种传染和神经退行性疾病之间有着有趣的联系，但是否 感染疾病如何影响ADRD风险仍未得到充实。这个问题尤其是紧迫的 在宽度宽度SARS-COV-2感染受到严重影响的全球 公共卫生。越来越多的证据表明，被SARS-COV-2感染的人很大一部分可能 经历大量和持久的后遗症，包括认知能力下降和神经系统缺陷。许多 仍然存在未知数，包括长期结局以及COVID-19疫苗接种和病毒变异的作用 修改SARS-COV-2感染对认知能力下降和ADRD风险的影响。这提出了F99/K00 项目旨在使用完整的纵向数据集和两个具体目标来解决这些差距 严格，高级流行病学和统计方法。 AIM 1（F99论文阶段：2023-2025）将 使用先前确定的COVID-19脑磁共振成像（MRI）签名区域来推断 感染对ADRD风险的长期影响通过大脑结构变化。 COVID-19-MRI签名区域 建立大脑区域，在SARS- COV-2感染（在一项纵向MRI研究中鉴定）。候选人将量化 英国生物库参与者的Covid-19-19-MRI签名区域和未来的ADRD风险。目标2（k00 博士后阶段：2025-2029）将评估SARS-COV-2的疫苗接种状况和时间的影响 关于认知结果和ADRD的感染，在Covid-19-19中的冲浪者中。候选人将使用来自 电子健康记录（EHR）和全国代表人群。方法论创新包括 使用神经影像学，因果生存分析，用于分类算法的机器学习方法 作为多个数据源（即来自EHR的临床数据和同类研究的调查数据）。这个建议 直接回应研究Covid-19对ADRD风险和认知的呼吁 阿尔茨海默氏症的项目法（NAPA）。该建议将候选人的定量专业知识扩展到高级 临床和生物学观点培训ADRD以及因果推理的衰老方法 研究。强大的跨学科心态团队和出色的支持培训环境 加利福尼亚大学，旧金山大学（F99）和马萨诸塞州综合医院（K00）提供 候选人填补有关传染病和免疫相关的重要科学差距的基础 认知衰老和ADRD的决定因素，包括感染SARS-COV-2。