{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T23:19:01Z","timestamp":1792019941111,"version":"4.4.0"},"reference-count":169,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T00:00:00Z","timestamp":1748217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cognitive dysfunction represents one of the most persistent and disabling features of Long COVID, yet its molecular underpinnings remain incompletely understood. This narrative review synthesizes current evidence on the pathophysiological mechanisms linking SARS-CoV-2 infection to long-term neurocognitive sequelae. Key processes include persistent neuroinflammation, blood\u2013brain barrier (BBB) disruption, endothelial dysfunction, immune dysregulation, and neuroendocrine imbalance. Microglial activation and cytokine release (e.g., IL-6, TNF-\u03b1) promote synaptic dysfunction and neuronal injury, while activation of inflammasomes such as NLRP3 amplifies CNS inflammation. Vascular abnormalities, including microthrombosis and BBB leakage, facilitate the infiltration of peripheral immune cells and neurotoxic mediators. Hypothalamic\u2013pituitary\u2013adrenal axis dysfunction and reduced vagal tone further exacerbate systemic inflammation and autonomic imbalance. Biomarkers such as GFAP, NFL, IL-6, and S100B have been associated with both neuroinflammation and cognitive symptoms. Notably, transcriptomic signatures in Long COVID overlap with those observed in Alzheimer\u2019s disease, highlighting shared pathways involving tau dysregulation, oxidative stress, and glial reactivity. Understanding these mechanisms is critical for identifying at-risk individuals and developing targeted therapeutic strategies. This review underscores the need for longitudinal research and integrative biomarker analysis to elucidate the molecular trajectory of cognitive impairment in Long COVID.<\/jats:p>","DOI":"10.3390\/ijms26115102","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T11:12:57Z","timestamp":1748344377000},"page":"5102","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["The Molecular Mechanisms of Cognitive Dysfunction in Long COVID: A Narrative Review"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2207-5129","authenticated-orcid":false,"given":"Elena","family":"Popa","sequence":"first","affiliation":[{"name":"Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 16 Universitatii Str., 700115 Iasi, Romania"},{"name":"Department of Family Medicine, Preventive Medicine and Interdisciplinary, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, Universitatii Str. 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrei Emilian","family":"Popa","sequence":"additional","affiliation":[{"name":"\u201cProf. Dr. Nicolae Oblu\u201d Emergency Clinic Hospital, 700309 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihaela","family":"Poroch","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 16 Universitatii Str., 700115 Iasi, Romania"},{"name":"Department of Family Medicine, Preventive Medicine and Interdisciplinary, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, Universitatii Str. 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2503-5395","authenticated-orcid":false,"given":"Vladimir","family":"Poroch","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 16 Universitatii Str., 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica Iuliana","family":"Ungureanu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 16 Universitatii Str., 700115 Iasi, Romania"},{"name":"Department of Family Medicine, Preventive Medicine and Interdisciplinary, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, Universitatii Str. 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Maria","family":"Slanina","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 16 Universitatii Str., 700115 Iasi, Romania"},{"name":"Department of Family Medicine, Preventive Medicine and Interdisciplinary, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, Universitatii Str. 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnes","family":"Bacusca","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 16 Universitatii Str., 700115 Iasi, Romania"},{"name":"Department of Family Medicine, Preventive Medicine and Interdisciplinary, \u201cGrigore T. 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