{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T11:13:51Z","timestamp":1777634031204,"version":"3.51.4"},"reference-count":23,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":27,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["1R44NS172072\u2010A1"],"award-info":[{"award-number":["1R44NS172072\u2010A1"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Academic Emergency Medicine"],"published-print":{"date-parts":[[2026,4]]},"abstract":"ABSTRACT<\/jats:title>\n \n Objectives<\/jats:title>\n Blood\u2010based biomarkers for traumatic brain injury (TBI) are increasingly integrated into diagnostic algorithms, but their interpretation may be confounded by age\u2010related neurological changes. This study quantified the relative effects of age and TBI on biomarker concentrations to determine whether age\u2010related variation approaches or exceeds that associated with injury.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Serum biomarkers were analyzed from 762 adults enrolled in the HeadSMART II and HeadSMART Geriatric studies, including healthy controls (\n n<\/jats:italic>\n \u2009=\u200988), non\u2010head trauma controls (\n n<\/jats:italic>\n \u2009=\u200999), and mild TBI patients (GCS 13\u201315,\n n<\/jats:italic>\n \u2009=\u2009575). Participants were categorized by age (18\u201340, 41\u201364, 65\u201374, \u2265\u200975\u2009years). Six TBI\u2010relevant biomarkers (glial fibrillary acidic protein [GFAP], brain\u2010derived neurotrophic factor [BDNF], neurogranin [NRGN], \u03b1\u2010synuclein [SNCA], suppression of tumorigenicity 2 [ST2], and von Willebrand factor [vWF]) were quantified using validated immunoassays (BRAINBox Solutions). Biomarker levels were compared using two\u2010way ANOVA, and the relative effects of age and injury were estimated using Cohen's\n f<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Age significantly influenced several biomarkers. GFAP showed strong age\u2010related increases, with significant elevations across age strata (\n p<\/jats:italic>\n \u2009<\u20090.001), exceeding the effect of head injury alone. vWF also increased significantly with age (\n p<\/jats:italic>\n \u2009<\u20090.001), while ST2 did not show a main effect of age (\n p<\/jats:italic>\n \u2009=\u20090.404), although age interacted with group (\n p<\/jats:italic>\n \u2009<\u20090.001). SNCA demonstrated modest age effects (\n p<\/jats:italic>\n \u2009=\u20090.001), particularly in older trauma and TBI participants. NRGN showed no significant age\u2010related changes (\n p<\/jats:italic>\n \u2009=\u20090.454), and BDNF exhibited age effects within interaction terms (\n p<\/jats:italic>\n \u2009<\u20090.001). Overall, age\u2010associated effect sizes for GFAP and vWF were comparable to, or greater than, those of head injury.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Age exerts substantial influence on circulating biomarker concentrations, particularly GFAP and vWF, often rivaling or exceeding TBI\u2010related changes. Diagnostic algorithms that fail to adjust for age may risk misclassification, especially among older adults, underscoring the need for age\u2010normalized biomarker interpretation.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/acem.70298","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T15:24:08Z","timestamp":1777389848000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Age\u2010Specific Clinical Biomarker Ranges in Acute Head Injury, Non\u2010\n TBI<\/scp>\n Trauma, and Healthy Control Subjects in the Emergency Department"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9069-2439","authenticated-orcid":false,"given":"Katherine D.","family":"Mayes","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine Virginia Tech Carilion School of Medicine Roanoke Virginia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy E.","family":"Van Meter","sequence":"additional","affiliation":[{"name":"BRAINBox Solutions, Inc Richmond Virginia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nazanin","family":"Mirshahi","sequence":"additional","affiliation":[{"name":"BRAINBox Solutions, Inc Richmond Virginia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sally","family":"Boyd","sequence":"additional","affiliation":[{"name":"BRAINBox Solutions, Inc Richmond Virginia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle","family":"Sandsmark","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Pennsylvania Perelman School of Medicine Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katya","family":"Rascovsky","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Pennsylvania Perelman School of Medicine Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramon","family":"Diaz\u2010Arrastia","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Pennsylvania Perelman School of Medicine Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin","family":"Weppner","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Virginia Tech Carilion School of Medicine Roanoke Virginia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W. Frank","family":"Peacock","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine Baylor College of Medicine Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Damon R.","family":"Kuehl","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine Virginia Tech Carilion School of Medicine Roanoke Virginia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"the HeadSMART II Investigators","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12093283"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/med.21295"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2017.5371"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/acem.13844"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3171\/2019.9.FOCUS19652"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(25)00154\u20101"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737159.2024.2306876"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/02699052.2017.1357836"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2023.110680"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S125620"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13898"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916\u2010024\u201003418\u20108"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2015.0825"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22020725"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00475"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2020.584743"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.733712"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci13050707"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2021.0455"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1053\/apmr.2003.50091"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2008.07.007"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20020257"},{"issue":"1","key":"e_1_2_10_24_1","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1186\/s12882-025-04130-2","article-title":"Plasma Concentrations of Neurofilament Light, p\u2010Tau231 and Glial Fibrillary Acidic Protein Are Elevated in Patients With Chronic Kidney Disease and Correlate With Measured Glomerular Filtration Rate","volume":"26","author":"Axelsson T.","year":"2025","journal-title":"BMC Nephrology"}],"container-title":["Academic Emergency Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acem.70298","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acem.70298","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acem.70298","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T05:01:58Z","timestamp":1777438918000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acem.70298"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":23,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1111\/acem.70298"],"URL":"https:\/\/doi.org\/10.1111\/acem.70298","archive":["Portico"],"relation":{},"ISSN":["1069-6563","1553-2712"],"issn-type":[{"value":"1069-6563","type":"print"},{"value":"1553-2712","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"2025-10-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70298"}}