{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T20:07:54Z","timestamp":1789416474436,"version":"build-2803163510"},"reference-count":92,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008871","name":"Yunnan Province Science and Technology Department","doi-asserted-by":"publisher","award":["No.202501AS070139"],"award-info":[{"award-number":["No.202501AS070139"]}],"id":[{"id":"10.13039\/501100008871","id-type":"DOI","asserted-by":"publisher"}]},{"award":["No.202501AS070139"],"award-info":[{"award-number":["No.202501AS070139"]}],"id":[{"id":"https:\/\/ror.org\/03whqdf70","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Traumatic brain injury (TBI), a major cause of persistent cognitive impairment (CI), increases the long-term risk of developing dementia, including Alzheimer\u2019s disease (AD). To elucidate this association, we systematically reviewed fluid biomarkers linked to post-TBI cognitive outcomes. A comprehensive search of the PubMed, Embase, and Cochrane Library databases was performed. A total of 29 clinical studies were included, reporting on several biomarkers related to neural injury and repair, AD-like pathology, and inflammation. Among these, neurofilament light chain (NfL), ubiquitin C-terminal hydrolase L1, total tau, and glial fibrillary acidic protein (GFAP) were consistently associated with CI and brain atrophy across various TBI severities and stages. Notably, certain biomarkers assessed during the acute phase (within 7 days post-injury), such as brain-derived neurotrophic factor, neuron-specific enolase, and interleukin-1\u03b2, showed significant correlations with CI. In contrast, elevated levels of GFAP and NfL measured during the recovery phase (6 months to 8 years post-injury) were significantly associated with TBI-related CI (TBI-CI). The findings also highlighted that axonal injury, glial activation, neuroinflammation, neuronal damage, and degeneration drive TBI-CI, with tau pathology and synaptic dysfunction emerging as potential bridges from TBI to AD. This review underscores the critical temporal dynamics of fluid biomarkers in TBI-CI, revealing that stage-specific biomarker profiles mirror distinct underlying pathophysiological processes. Future longitudinal studies should focus on well-characterized patient subgroups, adopt standardized diagnostic criteria, and integrate fluid biomarkers with neuroimaging and genetic data.<\/jats:p>","DOI":"10.3390\/ijms27104274","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T07:49:09Z","timestamp":1778572149000},"page":"4274","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Fluid Biomarkers of Cognitive Impairments Following Traumatic Brain Injury: A Systematic Review and Meta Analysis"],"prefix":"10.3390","volume":"27","author":[{"given":"Yingdi","family":"Liao","sequence":"first","affiliation":[{"name":"First Clinical Medical College, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianna","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youyang","family":"Zhu","sequence":"additional","affiliation":[{"name":"First Clinical Medical College, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirong","family":"Ye","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinqing","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhichao","family":"Niu","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luoqing","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Lei","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peixin","family":"Guo","sequence":"additional","affiliation":[{"name":"The College Based Key Laboratory of Yunnan in Aromatic Chinese Herbal Research, Kunming 650500, China"},{"name":"College of Ethnic Medicine, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhuan","family":"Xie","sequence":"additional","affiliation":[{"name":"The College Based Key Laboratory of Yunnan in Aromatic Chinese Herbal Research, Kunming 650500, China"},{"name":"Science and Technology Department, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1016\/j.amepre.2025.01.001","article-title":"Global Burden of Traumatic Brain Injury in 204 Countries and Territories From 1990 to 2021","volume":"68","author":"Zhong","year":"2025","journal-title":"Am. 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