Examining four blood biomarkers for the detection of acute intracranial abnormalities following mild traumatic brain injury in older adults

Grant L. Iverson, Mira Minkkinen, Justin E. Karr, Ksenia Berghem, Henrik Zetterberg, Kaj Blennow, Jussi P. Posti, Teemu M. Luoto

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Blood-based biomarkers have been increasingly studied for diagnostic and prognostic purposes in patients with mild traumatic brain injury (MTBI). Biomarker levels in blood have been shown to vary throughout age groups. Our aim was to study four blood biomarkers, glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), neurofilament light (NF-L), and total tau (t-tau), in older adult patients with MTBI. The study sample was collected in the emergency department in Tampere University Hospital, Finland, between November 2015 and November 2016. All consecutive adult patients with head injury were eligible for inclusion. Serum samples were collected from the enrolled patients, which were frozen and later sent for biomarker analyses. Patients aged 60 years or older with MTBI, head computed tomography (CT) imaging, and available biomarker levels were eligible for this study. A total of 83 patients (mean age = 79.0, SD = 9.58, range = 60–100; 41.0% men) were included in the analysis. GFAP was the only biomarker to show statistically significant differentiation between patients with and without acute head CT abnormalities [U(83) = 280, p < 0.001, r = 0.44; area under the curve (AUC) = 0.79, 95% CI = 0.67–0.91]. The median UCH-L1 values were modestly greater in the abnormal head CT group vs. normal head CT group [U (83) = 492, p = 0.065, r = 0.20; AUC = 0.63, 95% CI = 0.49–0.77]. Older age was associated with biomarker levels in the normal head CT group, with the most prominent age associations being with NF-L (r = 0.56) and GFAP (r = 0.54). The results support the use of GFAP in detecting abnormal head CT findings in older adults with MTBIs. However, small sample sizes run the risk for producing non-replicable findings that may not generalize to the population and do not translate well to clinical use. Further studies should consider the potential effect of age on biomarker levels when establishing clinical cut-off values for detecting head CT abnormalities.

Original languageEnglish
Article number960741
JournalFrontiers in Neurology
Volume13
DOIs
StatePublished - Nov 22 2022

Bibliographical note

Publisher Copyright:
Copyright © 2022 Iverson, Minkkinen, Karr, Berghem, Zetterberg, Blennow, Posti and Luoto.

Funding

The study was financially supported by the Finnish State Research Funding, and the Finnish Medical Society Duodecim. TL and JP have received funding from Government's Special Financial Transfer tied to academic research in Health Sciences (Finland). JP has received funding from the Academy of Finland (#17379), Emil Aaltonen Foundation sr and the Maire Taponen Foundation. KajB acknowledges funding from the Torsten S\u00F6derberg Foundation, the Swedish Research Council, and the Swedish Brain Foundation. HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712 and #101053962), Swedish State Support for Clinical Research (#ALFGBG-71320), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), the AD Strategic Fund and the Alzheimer's Association (#ADSF-21-831376-C, #ADSF-21-831381-C and #ADSF-21-831377-C), the Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen f\u00F6r Gamla Tj\u00E4narinnor, Hj\u00E4rnfonden, Sweden (#FO2019-0228), the European Union's Horizon 2020 research and innovation programme under the Marie Sk\u0142odowska-Curie grant agreement No 860197 (MIRIADE), the European Union Joint Programme\u2014Neurodegenerative Disease Research (JPND2021-00694), and the UK Dementia Research Institute at UCL (UKDRI-1003). GI acknowledges unrestricted philanthropic support from the Mooney-Reed Charitable Foundation, ImPACT Applications, Inc., the Heinz Family Foundation, and the Schoen Adams Research Institute at Spaulding Rehabilitation. The above entities were not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication.

FundersFunder number
Heinz Family Foundation
Familjen Erling-Perssons Stiftelse
Suomalainen Lääkäriseura Duodecim
Schoen Adams Research Institute
Horizon 2020 Framework Programme
Emil Aaltosen Säätiö
European Commission
Maire Taposen Säätiö
Mooney-Reed Charitable Foundation
Olav Thon Stiftelsen
Torsten Söderbergs Stiftelse
AD Strategic Fund
Vetenskapsrådet
Horizon 2020
H2020 European Research Council101053962, 681712
H2020 European Research Council
European Union Joint Programme–Neurodegenerative Disease ResearchJPND2021-00694
Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment-21-831376-C, -21-831377-C
Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment
H2020 Marie Skłodowska-Curie Actions860197
H2020 Marie Skłodowska-Curie Actions
UK Dementia Research InstituteUKDRI-1003
UK Dementia Research Institute
Academy of Finland17379
Academy of Finland
Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden2018-02532
Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden
Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden2019-0228
Alzheimer's Drug Discovery Foundation201809-2016862
Alzheimer's Drug Discovery Foundation
Swedish State Support for Clinical Research-71320

    Keywords

    • biomarkers
    • computed tomography
    • glial fibrillary acidic protein
    • neurofilament light
    • total tau
    • traumatic brain injury
    • ubiquitin C-terminal hydrolase-L1

    ASJC Scopus subject areas

    • Neurology
    • Clinical Neurology

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