Long-term effects of COVID-19 on cerebrovascular function in patients with mild cognitive impairment
Authors: Owens Cameron , Mukli Peter , Bonin Pinto Camila , Detwiler Sam , Tarantini Stefano , Hoffmeister Jordan , Csiszar Anna , Ungvari Zoltan , Kirkpatrick Angelia , Prodan Calin , Yabluchanskiy Andriy 
Published: May 2023

Background: Dementia is the sixth leading cause of death in United States and causes significant disability in the aging population. Therefore, conversion of mild cognitive impairment (MCI) to dementia, and conditions affecting conversion (e.g., hypertension), is of the utmost public health concerns. COVID-19 has had a profound effect on the aging population with increased risk of cognitive dysfunction and cerebrovascular complications following recovery of infection. We have strong preliminary data that suggest COVID-19 increases progression rate from MCI to dementia compared to MCI patients with no COVID-19 history (56% vs 23%, respectively, p=0.011). However, mechanisms contributing to these findings have yet to be elucidated. Normal brain function is reliant on endothelium dependent cerebromicrovascular dilation to provide sufficient oxygen and nutrients to active neurons (neurovascular coupling [NVC]). Thus, due to COVID-19’s deleterious effects on the cerebrovasculature and association with cognitive impairment, it is necessary to investigate vascular mechanisms that may contribute to COVID-19 induced cognitive dysfunction. Our central hypothesis is that COVID-19 induces systemic endothelial dysfunction, impairing NVC responses and contributing to increased progression of MCI to dementia. Methods: We are addressing the central hypothesis through prospective follow-up design, assessing systemic and cerebrovascular function at baseline and 18-month follow-up in MCI patients with and without history of COVID-19 infection. We will collect 200 participants over the course of 3 years and progression to dementia data will be measured by semiannual evaluation in the Department of Neurology at the University of Oklahoma Health Sciences Center. Assessment of endothelial function was measured by laser speckle contrast imaging and flow mediated dilation studies. NVC responses were measured with functional near-infrared spectroscopy during cognitive stimulation with n-back test.Preliminary results: Our preliminary results were collected at baseline from 3 MCI patients with no history of cerebrovascular complications (1 COVID+ patient [77 years old, male]; 2 COVID- patients [55 and 65 years old, female]). COVID+ patient showed significant attenuation of NVC responses and peripheral macro- and microvascular endothelial function compared to COVID- patients. Conclusion: Preliminary data suggest that NVC and peripheral macro- and microvascular endothelium may be impaired in MCI patients with history of COVID-19 diagnosis. Further investigation into the role that COVID-19 has on cerebrovascular function and conversion to dementia will enhance the understanding of predisposing factors that influence progression to dementia. These findings may uncover a mechanism for how COVID-19 affects cognitive function, paving the way for future therapeutic interventions targeting neurovascular uncoupling as a prominent feature in the conversion to dementia. American Heart Association (AHA834339), the National Institute on Aging of National Institutes of Health (R01AG075834), and the NIA-supported Geroscience Training Program in Oklahoma (T32AG052363) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.