# Neurovascular Uncoupling and Cognitive Impairments of Long COVID in Aging

> **NIH NIH R21** · MEDICAL COLLEGE OF WISCONSIN · 2022 · $273,000

## Abstract

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

## Key facts

- **NIH application ID:** 10537136
- **Project number:** 1R21AG077746-01A1
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Yang Wang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $273,000
- **Award type:** 1
- **Project period:** 2022-09-30 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10537136

## Citation

> US National Institutes of Health, RePORTER application 10537136, Neurovascular Uncoupling and Cognitive Impairments of Long COVID in Aging (1R21AG077746-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10537136. Licensed CC0.

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