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.

项目概要/摘要 阿尔茨海默病和阿尔茨海默病相关疾病 (ADRD) 的患病率不断上升，是一个重要的公众问题 COVID-19 大流行可能会加剧健康问题。传染病可能会增加ADRD 通过引起中枢神经系统的神经炎症和氧化损伤，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。尽管几种感染性疾病和神经退行性疾病之间存在着有趣的联系，但 传染病如何影响 ADRD 风险仍有待探索。这个问题特别紧迫 在 COVID-19 大流行期间，广泛的 SARS-CoV-2 感染严重影响了全球 公共卫生。越来越多的证据表明，很大一部分 SARS-CoV-2 感染者可能 经历严重且持久的后遗症，包括认知能力下降和神经系统缺陷。许多 仍存在未知数，包括长期结果以及 COVID-19 疫苗接种和病毒变体在疾病中的作用 改变 SARS-CoV-2 感染对认知能力下降和 ADRD 风险的影响。本次建议的F99/K00 该项目旨在通过补充纵向数据集和两个具体目标来解决这些差距 严格、先进的流行病学和统计方法。目标 1（F99 论文阶段：2023-2025）将 使用先前识别的 COVID-19 脑部磁共振成像 (MRI) 特征区域来推断 感染通过大脑结构变化对 ADRD 风险产生长期影响。 COVID-19 MRI 特征区域 包括 SARS 后皮质厚度和灰白质对比度降低的大脑区域 CoV-2 感染（在纵向 MRI 研究中发现）。候选人将量化之间的关联 英国生物银行参与者中的 COVID-19 MRI 特征区域和未来 ADRD 风险。目标 2（K00 博士后阶段：2025-2029）将评估SARS-CoV-2疫苗接种状态和时机的影响 感染对 COVID-19 幸存者认知结果和 ADRD 的影响。候选人将使用以下数据： 电子健康记录（EHR）和具有全国代表性的队列。方法论创新包括 使用神经影像学、因果生存分析、机器学习方法进行分类算法，以及 作为多个数据源（即来自 EHR 的临床数据和来自队列研究的调查数据）。这个提议 直接响应国家研究 COVID-19 对 ADRD 风险和认知影响的号召 阿尔茨海默病项目法案 (NAPA)。该提案通过先进的技术扩展了候选人的定量专业知识 ADRD 的临床和生物学观点以及衰老因果推理方法的培训 研究。强大的跨学科导师团队和出色的支持性培训环境 加州大学旧金山分校 (F99) 和麻省总医院 (K00) 提供 为候选人填补传染病和免疫相关的重要科学空白奠定基础 认知衰老和 ADRD 的决定因素，包括 SARS-CoV-2 感染。