Neurovascular Uncoupling and Cognitive Impairments of Long COVID in Aging

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