Age‐Specific Clinical Biomarker Ranges in Acute Head Injury, Non‐TBI Trauma, and Healthy Control Subjects in the Emergency Department.

Objectives: Blood‐based biomarkers for traumatic brain injury (TBI) are increasingly integrated into diagnostic algorithms, but their interpretation may be confounded by age‐related neurological changes. This study quantified the relative effects of age and TBI on biomarker concentrations to determi...

Full description

Bibliographic Details
Published in:Academic Emergency Medicine Vol. 33; no. 4; pp. 1 - 12
Main Authors: Mayes, Katherine D., Van Meter, Timothy E., Mirshahi, Nazanin, Boyd, Sally, Sandsmark, Danielle, Rascovsky, Katya, Diaz‐Arrastia, Ramon, Weppner, Justin, Peacock, W. Frank, Kuehl, Damon R.
Format: research tables/charts Journal Article
Published: Wiley-Blackwell Apr2026
Online Access:View this record in EBSCOhost
fields @attributes:
  recordID: 1
pdfLink:
plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=193366628&site=ehost-live
header:
  @attributes:
    shortDbName: ccm
    uiTerm: 193366628
    longDbName: CINAHL Complete
    uiTag: AN
  controlInfo:
    bkinfo:
    dissinfo:
    jinfo:
      jid:
        10696563
        Z27
      jtl: Academic Emergency Medicine
      issn: 10696563
      maglogo: Y
    pubinfo:
      dt: Apr2026
      vid: 33
      iid: 4
      pid: 480
      pub: Wiley-Blackwell
      place: Malden, Massachusetts
    artinfo:
      ui:
        193366628
        193366628
        193366628
        10.1111/acem.70298
        193366628
      ppf: 1
      ppct: 11
      formats:
      tig:
        atl: Age‐Specific Clinical Biomarker Ranges in Acute Head Injury, Non‐TBI Trauma, and Healthy Control Subjects in the Emergency Department.
      aug:
        au:
          Mayes, Katherine D.
          Van Meter, Timothy E.
          Mirshahi, Nazanin
          Boyd, Sally
          Sandsmark, Danielle
          Rascovsky, Katya
          Diaz‐Arrastia, Ramon
          Weppner, Justin
          Peacock, W. Frank
          Kuehl, Damon R.
        affil: Department of Emergency Medicine, Virginia Tech Carilion School of Medicine, Roanoke Virginia,, USA
      sug:
        subj:
          Age Factors
          Biological Markers Blood
          Head Injuries
          Trauma
          Emergency Service
          Brain Injuries Diagnosis
          Human
          Adolescence
          Adult
          Middle Age
          Aged
          Aged, 80 and Over
          Male
          Female
          Brain-Derived Neurotrophic Factor Blood
          Synucleins Blood
          Blood Coagulation Factors Blood
          Cytoskeletal Proteins Blood
          Nerve Tissue Proteins Blood
          Carrier Proteins Blood
          Immunoassay
          Two-Way Analysis of Variance
          Prospective Studies
          Nonexperimental Studies
          Secondary Analysis
          Funding Source
          Descriptive Statistics
          Trauma Centers
          Data Analysis Software
          Kruskal-Wallis Test
          Adolescent: 13-18 years
          Adult: 19-44 years
          Middle Aged: 45-64 years
          Aged: 65+ years
          Aged, 80 & over
          Male
          Female
      ab: Objectives: Blood‐based biomarkers for traumatic brain injury (TBI) are increasingly integrated into diagnostic algorithms, but their interpretation may be confounded by age‐related neurological changes. This study quantified the relative effects of age and TBI on biomarker concentrations to determine whether age‐related variation approaches or exceeds that associated with injury. Methods: Serum biomarkers were analyzed from 762 adults enrolled in the HeadSMART II and HeadSMART Geriatric studies, including healthy controls (n = 88), non‐head trauma controls (n = 99), and mild TBI patients (GCS 13–15, n = 575). Participants were categorized by age (18–40, 41–64, 65–74, ≥ 75 years). Six TBI‐relevant biomarkers (glial fibrillary acidic protein [GFAP], brain‐derived neurotrophic factor [BDNF], neurogranin [NRGN], α‐synuclein [SNCA], suppression of tumorigenicity 2 [ST2], and von Willebrand factor [vWF]) were quantified using validated immunoassays (BRAINBox Solutions). Biomarker levels were compared using two‐way ANOVA, and the relative effects of age and injury were estimated using Cohen's f. Results: Age significantly influenced several biomarkers. GFAP showed strong age‐related increases, with significant elevations across age strata (p < 0.001), exceeding the effect of head injury alone. vWF also increased significantly with age (p < 0.001), while ST2 did not show a main effect of age (p = 0.404), although age interacted with group (p < 0.001). SNCA demonstrated modest age effects (p = 0.001), particularly in older trauma and TBI participants. NRGN showed no significant age‐related changes (p = 0.454), and BDNF exhibited age effects within interaction terms (p < 0.001). Overall, age‐associated effect sizes for GFAP and vWF were comparable to, or greater than, those of head injury. Conclusions: Age exerts substantial influence on circulating biomarker concentrations, particularly GFAP and vWF, often rivaling or exceeding TBI‐related changes. Diagnostic algorithms that fail to adjust for age may risk misclassification, especially among older adults, underscoring the need for age‐normalized biomarker interpretation.
      pubtype: Academic Journal
      doctype:
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
    refInfo:
    holdings:
      @attributes:
        islocal: N