Neurovascular Coupling in Hypertensive COVID‐19 Survivors Medicated With Different Classes of RAS Inhibitors: A Pilot Study

Background Hypertension poses an increased risk of Alzheimer’s disease (AD). Coronavirus disease 2019 (COVID‐19) may exacerbate this risk by affecting the Renin‐Angiotensin system (RAS), which contributes to the regulation of neurovascular coupling (NVC). NVC is a mechanism that optimizes cerebral blood flow (CBF) to meet the metabolic and waste‐removal needs of the brain. Disrupted NVC may predispose individuals to AD through hypoxia‐related protein changes and suboptimal protein‐waste removal from the brain. Several studies reported reduced CBF in long‐haul COVID‐19 patients. Among antihypertensive medicines that target the RAS, angiotensin receptor blockers (ARBs), but not angiotensin‐converting enzyme inhibitors (ACEIs), were previously found to regulate CBF. Therefore, we hypothesized that, if taken during and after a COVID‐19 episode, ARBs rather than ACEIs would be protective against long‐term CBF dysregulation. Method We quantified NVC through a novel analysis paradigm that takes advantage of simultaneous resting‐state electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). We obtained scans from older adult participants (aged 55‐80), including healthy controls and hypertensive COVID‐19 survivors medicated with ARBs or ACEIs during their COVID‐19 infection (occurring 3‐27 months before scanning). Hidden Markov modeling on source‐localized EEG was used to detect transient electrophysiological activity in distinct neural networks. A rapid event‐related fMRI analysis deconvolved the blood oxygenation level‐dependent (BOLD) changes evoked by the network‐specific electrophysiological activations. NVC was measured as the slope of vascular BOLD changes over the time‐locked electrophysiological neural changes. Result In this pilot study, the default mode network (DMN) showed differences in NVC between the hypertensive COVID‐19 survivors and the healthy control group. Crucially, the ARB‐medicated subgroup, like the control group, showed the BOLD response in the DMN regions time‐locked to the DMN electrophysiological activations; NVC differences between the ARB‐medicated and control groups did not reach significance. In contrast, the ACEI‐medicated subgroup showed a reduced NVC in the DMN relative to the control group. Conclusion The DMN, which is linked to memory dysfunction in AD, may be vulnerable to NVC disruptions, given its high metabolic demands. Hypertension management with ARBs may reduce COVID‐19’s effects on cerebrovascular