Neurovascular Uncoupling and Cognitive Impairments of Long COVID in Aging

衰老过程中长新冠病毒的神经血管解偶联和认知障碍

• 批准号: 10537136
• 负责人: Yang Wang
• 金额: $ 27.3万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-30 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10537136
• 关键词: 2019-nCoV; Acute; Affect; Age; Aging; Attention; Biological Markers; Blood flow; Brain; COVID-19; COVID-19 pandemic; COVID-19 patient; Case Study; Cerebrovascular Circulation; Cerebrum; Clinical Trials; Clinical assessments; Contracts; Data; Disease; Education; Elderly; Functional Magnetic Resonance Imaging; Functional disorder; Future; Gender; Goals; Health; Hospitalization; Hypoxia; Impaired cognition; Individual; Infection; Injury; Intervention; Knowledge; Lead; Link; Long COVID; Magnetic Resonance Imaging; Measurement; Measures; Mediating; Memory; Methodology; Methods; Microcirculation; Modeling; Nerve Degeneration; Neurobehavioral Manifestations; Neurocognitive; Neurocognitive Deficit; Neurologic; Neurologic Symptoms; Neurons; Neurophysiology - biologic function; Outcome Measure; Participant; Pathology; Patients; Pattern; Perfusion; Play; Psyche structure; Public Health; Quality of life; Recovery; Regulation; Reproducibility; Research; Rest; Role; SARS-CoV-2 infection; Series; Short-Term Memory; Signal Transduction; Societies; Symptoms; System; Techniques; Testing; Time; Work; age related; age related neurodegeneration; aged; arterial spin labeling; base; blood oxygen level dependent; brain fog; cerebrovascular; cognitive function; cognitive task; cognitive testing; daily functioning; endocannabinoid signaling; endogenous cannabinoid system; experience; experimental study; hemodynamics; improved; innovation; interest; neurobiological mechanism; neuroimaging; neuroinflammation; neurologic sequelae of COVID-19; neurophysiology; neuroregulation; neurovascular; neurovascular coupling; neurovascular injury; older patient; persistent symptom; post-COVID-19; relating to nervous system; response; specific biomarkers; tissue oxygenation

Project Summary/Abstract The COVID-19 pandemic is having a devastating impact on public health, societies, and economies worldwide. Emerging data indicate that a substantial proportion of patients recovered from the acute stages of Coronavirus disease 2019 (COVID-19) are suffering a constellation of persistent symptoms with onset after infection, often referred to as "Long COVID", which severely affect the daily function and quality of life of those patients. While aged individuals are particularly vulnerable to this disease, there is growing concern about neurological and neurodegenerative sequelae of COVID-19 in aging. While increasing evidence shows that COVID-19 often causes neurological symptoms via microvascular injuries and hypoxia in the brain, we hypothesize that neurovascular uncoupling is the primary neurophysiological mechanism underlying the cognitive impairments of Long COVID in aging. Whereas cerebral blood flow (CBF) can be estimated using the arterial spin labeling (ASL) perfusion MRI, the functional MRI (fMRI) based on the BOLD (Blood-oxygen-level-dependent) measures neuronal activity indirectly. Recently, we have developed an innovative multiband and multi-echo (MBME) BOLD/ASL MRI sequence that enables simultaneous measurement of hemodynamic response function and CBF to detect potential neurovascular uncoupling. This proof-of-concept study will investigate elderly patients (n=40) at 12+ months recovered from mild COVID-19 with persistent cognitive symptoms onset after contracting COVID-19, in comparison with age, gender and education matched health control (HC) participants (n=40). Using advanced neuroimaging, we will determine the relationships between measures of task-evoked neurovascular uncoupling patterns and long-lasting cognitive impairments of Long COVID in aging (Aim 1), determine the relationships of resting-state dynamic neurovascular uncoupling and brain network function alterations and persistent cognitive impairments of Long COVID in aging (Aim 2), and evaluate the associations of endocannabinoid signaling system (ECS) measures and neurovascular uncoupling patterns and cognitive impairments of Long COVID in aging (Aim 3). This work has high scientific and

项目概要/摘要 COVID-19 大流行正在对全世界的公共卫生、社会和经济产生毁灭性影响。 新数据表明，相当一部分患者已从冠状病毒急性期康复 2019 年新冠肺炎 (COVID-19) 患者通常会在感染后出现一系列持续症状 被称为“长新冠病毒”，严重影响患者的日常功能和生活质量。尽管 老年人特别容易感染这种疾病，人们越来越担心神经系统和疾病 衰老过程中 COVID-19 的神经退行性后遗症。虽然越来越多的证据表明，COVID-19 经常 通过微血管损伤和大脑缺氧引起神经系统症状，我们假设 神经血管解偶联是认知障碍的主要神经生理机制 长新冠在老龄化。而脑血流量 (CBF) 可以使用动脉自旋标记 (ASL) 来估计 灌注 MRI，基于 BOLD（血氧水平依赖）测量的功能 MRI (fMRI) 间接的神经元活动。最近，我们开发了一种创新的多频段和多回波（MBME） BOLD/ASL MRI 序列可同时测量血流动力学反应函数和 CBF 检测潜在的神经血管解偶联。这项概念验证研究将调查老年患者 (n=40) 在 12 个月以上时从轻度 COVID-19 中恢复，但在感染后出现持续的认知症状 与年龄、性别和教育程度相匹配的健康对照 (HC) 参与者 (n=40) 相比，COVID-19。 使用先进的神经影像学，我们将确定任务诱发测量之间的关系 衰老过程中 Long COVID 的神经血管解偶联模式和长期认知障碍（目标 1）， 确定静息态动态神经血管解偶联与脑网络功能的关系 衰老过程中长新冠病毒的改变和持续性认知障碍（目标 2），并评估其中的关联 内源性大麻素信号系统（ECS）测量和神经血管解偶联模式和认知的 长新冠肺炎对衰老的损害（目标 3）。本工作具有较高的科学性和