{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:22:13Z","timestamp":1792178533444,"version":"4.4.0"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2022,4,4]],"date-time":"2022-04-04T00:00:00Z","timestamp":1649030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"crossref","award":["FP7-270259"],"award-info":[{"award-number":["FP7-270259"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Medical Research Council","award":["G9439390"],"award-info":[{"award-number":["G9439390"]}]},{"DOI":"10.13039\/501100000272","name":"UK National Institute of Health Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Biomedical Research Centre"},{"name":"Cambridge and the Technology Platform"},{"name":"Department of Health"},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"crossref","award":["BB\/H008217\/1"],"award-info":[{"award-number":["BB\/H008217\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Medical Research Council"},{"DOI":"10.13039\/501100000735","name":"University of Cambridge","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000735","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>There is substantial interest in the potential for traumatic brain injury to result in progressive neurological deterioration. While blood biomarkers such as glial fibrillary acid protein (GFAP) and neurofilament light have been widely explored in characterizing acute traumatic brain injury (TBI), their use in the chronic phase is limited. Given increasing evidence that these proteins may be markers of ongoing neurodegeneration in a range of diseases, we examined their relationship to imaging changes and functional outcome in the months to years following TBI.<\/jats:p>\n                  <jats:p>Two-hundred and three patients were recruited in two separate cohorts; 6 months post-injury (n\u2009=\u2009165); and &amp;gt;5 years post-injury (n\u2009=\u200938; 12 of whom also provided data \u223c8 months post-TBI). Subjects underwent blood biomarker sampling (n\u2009=\u2009199) and MRI (n\u2009=\u2009172; including diffusion tensor imaging). Data from patient cohorts were compared to 59 healthy volunteers and 21 non-brain injury trauma controls. Mean diffusivity and fractional anisotropy were calculated in cortical grey matter, deep grey matter and whole brain white matter. Accelerated brain ageing was calculated at a whole brain level as the predicted age difference defined using T1-weighted images, and at a voxel-based level as the annualized Jacobian determinants in white matter and grey matter, referenced to a population of 652 healthy control subjects.<\/jats:p>\n                  <jats:p>Serum neurofilament light concentrations were elevated in the early chronic phase. While GFAP values were within the normal range at \u223c8 months, many patients showed a secondary and temporally distinct elevations up to &amp;gt;5 years after injury. Biomarker elevation at 6 months was significantly related to metrics of microstructural injury on diffusion tensor imaging. Biomarker levels at \u223c8 months predicted white matter volume loss at &amp;gt;5 years, and annualized brain volume loss between \u223c8 months and 5 years. Patients who worsened functionally between \u223c8 months and &amp;gt;5 years showed higher than predicted brain age and elevated neurofilament light levels.<\/jats:p>\n                  <jats:p>GFAP and neurofilament light levels can remain elevated months to years after TBI, and show distinct temporal profiles. These elevations correlate closely with microstructural injury in both grey and white matter on contemporaneous quantitative diffusion tensor imaging. Neurofilament light elevations at \u223c8 months may predict ongoing white matter and brain volume loss over &amp;gt;5 years of follow-up. If confirmed, these findings suggest that blood biomarker levels at late time points could be used to identify TBI survivors who are at high risk of progressive neurological damage.<\/jats:p>","DOI":"10.1093\/brain\/awac126","type":"journal-article","created":{"date-parts":[[2022,4,4]],"date-time":"2022-04-04T09:32:15Z","timestamp":1649064735000},"page":"2064-2076","source":"Crossref","is-referenced-by-count":109,"title":["Post-acute blood biomarkers and disease progression in traumatic brain injury"],"prefix":"10.1093","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6044-9035","authenticated-orcid":false,"given":"Virginia F J","family":"Newcombe","sequence":"first","affiliation":[{"name":"University Division of Anaesthesia, Department of Medicine, University of Cambridge , Cambridge , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J","family":"Ashton","sequence":"additional","affiliation":[{"name":"Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg , Gothenburg , Sweden"},{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg , M\u00f6lndal , Sweden"},{"name":"King\u2019s College London, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Institute Clinical Neuroscience Institute , London , UK"},{"name":"Mental Health and Biomedical Research Unit for Dementia, Maudsley NIHR Biomedical Research Centre , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jussi P","family":"Posti","sequence":"additional","affiliation":[{"name":"Neurocenter, Department of Neurosurgery, Turku University Hospital and University of Turku , Turku , Finland"},{"name":"Turku Brain Injury Center, Turku University Hospital and University of Turku , Turku , Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Glocker","sequence":"additional","affiliation":[{"name":"Biomedical Image Analysis Group, Department of Computing, Imperial College London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Manktelow","sequence":"additional","affiliation":[{"name":"University Division of Anaesthesia, Department of Medicine, University of Cambridge , Cambridge , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doris A","family":"Chatfield","sequence":"additional","affiliation":[{"name":"University Division of Anaesthesia, Department of Medicine, University of Cambridge , Cambridge , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Winzeck","sequence":"additional","affiliation":[{"name":"University Division of Anaesthesia, Department of Medicine, University of Cambridge , Cambridge , UK"},{"name":"Biomedical Image Analysis Group, Department of Computing, Imperial College London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7042-7462","authenticated-orcid":false,"given":"Edward","family":"Needham","sequence":"additional","affiliation":[{"name":"University Division of Anaesthesia, Department of Medicine, University of Cambridge , Cambridge , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3231-7040","authenticated-orcid":false,"given":"Marta M","family":"Correia","sequence":"additional","affiliation":[{"name":"MRC (Medical Research Council) Cognition and Brain Sciences Unit, University of Cambridge , Cambridge , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy B","family":"Williams","sequence":"additional","affiliation":[{"name":"Wolfson Brain Imaging Centre, Department of Clinical Neurosciences , Cambridge , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5081-6604","authenticated-orcid":false,"given":"Joel","family":"Simr\u00e9n","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg , M\u00f6lndal , Sweden"},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital , M\u00f6lndal , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riikka S K","family":"Takala","sequence":"additional","affiliation":[{"name":"Perioperative Services, Intensive Care Medicine and Pain Management, Department of Anesthesiology and Intensive Care, Turku University Hospital, University of Turku , Turku , Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ari J","family":"Katila","sequence":"additional","affiliation":[{"name":"Perioperative Services, Intensive Care Medicine and Pain Management, Department of Anesthesiology and Intensive Care, Turku University Hospital, University of Turku , Turku , Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henna Riikka","family":"Maanp\u00e4\u00e4","sequence":"additional","affiliation":[{"name":"Neurocenter, Department of Neurosurgery, Turku University Hospital and University of Turku , Turku , Finland"},{"name":"Turku Brain Injury Center, Turku University Hospital and University of Turku , Turku , Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jussi","family":"Tallus","sequence":"additional","affiliation":[{"name":"Turku Brain Injury Center, Turku University Hospital and University of Turku , Turku , Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janek","family":"Frantz\u00e9n","sequence":"additional","affiliation":[{"name":"Neurocenter, Department of Neurosurgery, Turku University Hospital and University of Turku , Turku , Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg , M\u00f6lndal , Sweden"},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital , M\u00f6lndal , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olli","family":"Tenovuo","sequence":"additional","affiliation":[{"name":"Turku Brain Injury Center, Turku University Hospital and University of Turku , Turku , Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3930-4354","authenticated-orcid":false,"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg , M\u00f6lndal , Sweden"},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital , M\u00f6lndal , Sweden"},{"name":"Department of Neurodegenerative Disease, UCL Institute of Neurology , Queen Square, London , UK"},{"name":"UK Dementia Research Institute at UCL, University College London , London , UK"},{"name":"Hong Kong Center for Neurodegenerative Disease , Hong Kong , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3228-9692","authenticated-orcid":false,"given":"David K","family":"Menon","sequence":"additional","affiliation":[{"name":"University Division of Anaesthesia, Department of Medicine, University of Cambridge , Cambridge , 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