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ORIGINAL RESEARCH article
Front. Neurol.
Sec. Neuroinfectious Diseases
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1504573
This article is part of the Research Topic An Update on Neurological Disorders Post COVID-19 Infection Vol 2: cardiovascular effects, neuro-cardiac and neuro-respiratory autonomic dysfunctions View all 11 articles
Changes in Cerebrovascular Reactivity within Functional Networks in Older Adults with Long COVID
Provisionally accepted
Jessica Pommy 1
Alexander Cohen 2
Amarpreet Mahil 2 Laura Glass-Umfleet 3
Sara Jane Swanson 3
Malgorzata Franczak 3 Shawn Obarski 3 Kelly Ristow 2
Yang Wang 2,3,4*- 1 Department of Neurology, College of Medicine, The Ohio State University, Columbus, Ohio, United States
- 2 Department of Radiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
- 3 Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
- 4 Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
Cognitive symptoms are reported in the vast majority of individuals with long-COVID and there is growing support to suggest neurovascular mechanisms may play a role. Older adults are at increased risk for developing complications associated with COVID-19, including heightened risk for cognitive decline. Cerebrovascular Reactivity (CVR), a marker of neurovascular health, has been linked to age related cognitive decline and may play a role in long-COVID, however, this has not yet been explored. The present study examined group differences in CVR in 31 older adults with long-COVID compared to 31 cognitively unimpaired older adults without long-COVID symptoms. Follow up analyses were conducted to examine how CVR was associated with both subjective cognitive Altered Cerebrovascular Reactivity in Long-COVID symptoms and neuropsychological (NP) test performance. Using a subject specific approach, Distribution-Corrected Z-scores (DisCo-Z), analyses revealed the long-COVID group demonstrated significantly greater incidence of extreme CVR clusters within the brain (>100 voxels) and within functional networks thought to drive attention and executive function. Extreme positive CVR clusters were positively associated with greater number of subjective cognitive symptoms and negatively correlated with NP performance. These findings are among the first to provide a link between cognitive functioning in long-COVID and neurovascular changes relevant for aging and mechanistic studies of long-COVID.
Keywords: Long COVID1, neurovascular2, cerebrovascular reactivity3, functional MRI4, aging5, brain network6
Received: 01 Oct 2024; Accepted: 28 Feb 2025.
Copyright: © 2025 Pommy, Cohen, Mahil, Glass-Umfleet, Swanson, Franczak, Obarski, Ristow and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yang Wang, Department of Radiology, Medical College of Wisconsin, Milwaukee, 53226, Wisconsin, United States
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