{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T01:06:30Z","timestamp":1759971990188,"version":"build-2065373602"},"reference-count":0,"publisher":"Wiley","issue":"S17","license":[{"start":{"date-parts":[[2023,12,25]],"date-time":"2023-12-25T00:00:00Z","timestamp":1703462400000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hypertension poses an increased risk of Alzheimer\u2019s disease (AD). Coronavirus disease 2019 (COVID\u201019) may exacerbate this risk by affecting the Renin\u2010Angiotensin 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\u2010removal needs of the brain. Disrupted NVC may predispose individuals to AD through hypoxia\u2010related protein changes and suboptimal protein\u2010waste removal from the brain. Several studies reported reduced CBF in long\u2010haul COVID\u201019 patients. Among antihypertensive medicines that target the RAS, angiotensin receptor blockers (ARBs), but not angiotensin\u2010converting enzyme inhibitors (ACEIs), were previously found to regulate CBF. Therefore, we hypothesized that, if taken during and after a COVID\u201019 episode, ARBs rather than ACEIs would be protective against long\u2010term CBF dysregulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>We quantified NVC through a novel analysis paradigm that takes advantage of simultaneous resting\u2010state electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). We obtained scans from older adult participants (aged 55\u201080), including healthy controls and hypertensive COVID\u201019 survivors medicated with ARBs or ACEIs during their COVID\u201019 infection (occurring 3\u201027 months before scanning). Hidden Markov modeling on source\u2010localized EEG was used to detect transient electrophysiological activity in distinct neural networks. A rapid event\u2010related fMRI analysis deconvolved the blood oxygenation level\u2010dependent (BOLD) changes evoked by the network\u2010specific electrophysiological activations. NVC was measured as the slope of vascular BOLD changes over the time\u2010locked electrophysiological neural changes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Result<\/jats:title><jats:p>In this pilot study, the default mode network (DMN) showed differences in NVC between the hypertensive COVID\u201019 survivors and the healthy control group. Crucially, the ARB\u2010medicated subgroup, like the control group, showed the BOLD response in the DMN regions time\u2010locked to the DMN electrophysiological activations; NVC differences between the ARB\u2010medicated and control groups did not reach significance. In contrast, the ACEI\u2010medicated subgroup showed a reduced NVC in the DMN relative to the control group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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\u201019\u2019s effects on cerebrovascular regulation, preventing ischemic stroke, vascular dementia, and AD. Results replication is warranted.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.075882","type":"journal-article","created":{"date-parts":[[2023,12,25]],"date-time":"2023-12-25T07:04:45Z","timestamp":1703487885000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neurovascular Coupling in Hypertensive COVID\u201019 Survivors Medicated With Different Classes of RAS Inhibitors: A Pilot Study"],"prefix":"10.1002","volume":"19","author":[{"given":"Sarah E","family":"Guthrie","sequence":"first","affiliation":[{"name":"Massachusetts General Hospital, Charlestown, MA  USA"},{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA  USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John R","family":"Jacoby","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Charlestown, MA  USA"},{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA  USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah F","family":"Mellen","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Charlestown, MA  USA"},{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA  USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily M","family":"Valencia","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Charlestown, MA  USA"},{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA  USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine N","family":"Maina","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Charlestown, MA  USA"},{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA  USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christa B","family":"Michel","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Charlestown, MA  USA"},{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA  USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shrikanth M","family":"Yadav","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Charlestown, MA  USA"},{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA  USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Casey M","family":"Howard","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Charlestown, MA  USA"},{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA  USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David H","family":"Salat","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Charlestown, MA  USA"},{"name":"Neuroimaging Research for Veterans Center, VA Boston Healthcare System, Jamaica Plain, MA  USA"},{"name":"Harvard Medical School, Boston, MA  USA"},{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA  USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatiana A","family":"Sitnikova","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Charlestown, MA  USA"},{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA  USA"},{"name":"Harvard Medical School, Boston, MA  USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,12,25]]},"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.075882","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T18:23:12Z","timestamp":1759947792000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.075882"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12]]},"references-count":0,"journal-issue":{"issue":"S17","published-print":{"date-parts":[[2023,12]]}},"alternative-id":["10.1002\/alz.075882"],"URL":"https:\/\/doi.org\/10.1002\/alz.075882","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"type":"print","value":"1552-5260"},{"type":"electronic","value":"1552-5279"}],"subject":[],"published":{"date-parts":[[2023,12]]},"assertion":[{"value":"2023-12-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e075882"}}