Post-acute blood biomarkers and disease progression in traumatic brain injury.
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Authors
Ashton, Nicholas J
Posti, Jussi P
Glocker, Ben
Manktelow, Anne
Chatfield, Doris A
Winzeck, Stefan
Williams, Guy B
Takala, Riikka SK
Katila, Ari J
Maanpää, Henna Riikka
Tallus, Jussi
Frantzén, Janek
Blennow, Kaj
Tenovuo, Olli
Publication Date
2022-06-30Journal Title
Brain
ISSN
0006-8950
Publisher
Oxford University Press (OUP)
Language
English
Type
Article
This Version
AM
Metadata
Show full item recordCitation
Newcombe, V. F., Ashton, N. J., Posti, J. P., Glocker, B., Manktelow, A., Chatfield, D. A., Winzeck, S., et al. (2022). Post-acute blood biomarkers and disease progression in traumatic brain injury.. Brain https://doi.org/10.1093/brain/awac126
Abstract
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. Two-hundred and three patients were recruited in two separate cohorts; 6 months post-injury (n = 165); and >5 years post-injury (n = 38; 12 of whom also provided data ∼8 months post-TBI). Subjects underwent blood biomarker sampling (n = 199) and MRI (n = 172; 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. Serum neurofilament light concentrations were elevated in the early chronic phase. While GFAP values were within the normal range at ∼8 months, many patients showed a secondary and temporally distinct elevations up to >5 years after injury. Biomarker elevation at 6 months was significantly related to metrics of microstructural injury on diffusion tensor imaging. Biomarker levels at ∼8 months predicted white matter volume loss at >5 years, and annualized brain volume loss between ∼8 months and 5 years. Patients who worsened functionally between ∼8 months and >5 years showed higher than predicted brain age and elevated neurofilament light levels. 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 ∼8 months may predict ongoing white matter and brain volume loss over >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.
Sponsorship
Academy of Medical Sciences (unknown)
Biotechnology and Biological Sciences Research Council (BB/H008217/1)
Medical Research Council (G9439390)
European Commission (270259)
Embargo Lift Date
2023-06-02
Identifiers
External DOI: https://doi.org/10.1093/brain/awac126
This record's URL: https://www.repository.cam.ac.uk/handle/1810/335861
Rights
Attribution-NonCommercial 4.0 International
Licence URL: https://creativecommons.org/licenses/by-nc/4.0/
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