Vascular mechanisms leading to progression of mild cognitive impairment to dementia after COVID-19
Description: Dementia is currently the seventh leading cause of death among all diseases and one of the major causes of disability and dependency among older people. Mild cognitive impairment (MCI) is a prevalent neurocognitive disorder, which is considered a prodromal stage to dementia. A recent meta-analysis of 41 robust inception cohort studies reported that the adjusted annual conversion rate (ACR) of MCI cases to dementia in community settings is 4.9% (95% CI=1.6–9.9%). In the United States, over 70.7 million reported cases of COVID-19 have been confirmed as of January 24, 2022, resulting in over 866,000 deaths. We have strong preliminary evidence that COVID-19 infection significantly increases ACR of MCI to dementia in older individuals. Yet, the COVID-19 related mechanism(s) responsible for the increased progression of MCI to dementia are not understood. SARS-CoV-2 can infect the endothelial cells and thereby promote the genesis of vascular pathologies in the brain. Endothelial cells are also sensitive to the deleterious effects of inflammatory cytokines overproduced during COVID-19 infection. Accordingly, COVID-19 can promote persisting endothelial dysfunction. COVID-19 has also been causally linked to white matter lesions, manifested as cerebral white matter hyperintensities (WMHs) evident on CT and MRI brain scans of recovered COVID-19 patients, which are radiological signs of small vessel disease and resulting ischemic brain damage. Guided by our published results and strong preliminary data we propose to elucidate the role of cerebromicrovascular alterations in COVID-19-induced progression of MCI to dementia. Our central hypothesis is that COVID-19 promotes endothelial dysfunction, impairing neurovascular coupling (NVC) responses and promoting white matter damage, which contribute to the progression of MCI to dementia. A sub-hypothesis is that COVID-19 promotes cerebromicrovascular dysfunction by promoting endothelial senescence. Our hypothesis will be tested in the following aims: 1) Determine whether COVID-19 related increases in WMH burden predict conversion of MCI to dementia. 2) Determine whether COVID-19 related endothelial dysfunction and NVC impairment predict conversion of MCI to dementia.
Funder: American Heart Association
Amount: $906,700
Funding type: research
Funder scheme: COVID CV Consequences
Start date: 2022-04-01
End date: 2025-03-31
Investigators: Andriy Yabluchanskiy, Andriy Yabluchanskiy
Institution: Board of Regents of the University of Oklahoma, Health Sciences Center
Funded outputs count: 17
Funder award ID: 966924
OpenAlex ID: G2498661258