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 language | English |
|---|---|
| Article number | 960741 |
| Journal | Frontiers in Neurology |
| Volume | 13 |
| DOIs | |
| State | Published - 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.
| Funders | Funder 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 Council | 101053962, 681712 |
| H2020 European Research Council | |
| European Union Joint Programme–Neurodegenerative Disease Research | JPND2021-00694 |
| 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 Actions | 860197 |
| H2020 Marie Skłodowska-Curie Actions | |
| UK Dementia Research Institute | UKDRI-1003 |
| UK Dementia Research Institute | |
| Academy of Finland | 17379 |
| Academy of Finland | |
| Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden | 2018-02532 |
| Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden | |
| Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden | 2019-0228 |
| Alzheimer's Drug Discovery Foundation | 201809-2016862 |
| 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