TY  - JOUR
PY  - 2023//
TI  - Longitudinal associations between blood biomarkers and white-matter MRI in sport-related concussion: a study of the NCAA-DoD CARE Consortium
JO  - Neurology
A1  - Wu, Yu-Chien
A1  - Wen, Qiuting
A1  - Thukral, Rhea
A1  - Yang, Ho-Ching
A1  - Gill, Jessica M.
A1  - Gao, Sujuan
A1  - Lane, Kathleen A.
A1  - Meier, Timothy B.
A1  - Riggen, Larry D.
A1  - Harezlak, Jaroslaw
A1  - Giza, Christopher C.
A1  - Goldman, Joshua
A1  - Guskiewicz, Kevin M.
A1  - Mihalik, Jason P.
A1  - LaConte, Stephen M.
A1  - Duma, Stefan M.
A1  - Broglio, Steven P.
A1  - Saykin, Andrew J.
A1  - McAllister, Thomas Walker
A1  - McCrea, Michael A.
SP  - ePub
EP  - ePub
VL  - ePub
IS  - ePub
N2  - OBJECTIVE: To study longitudinal associations between blood-based neural biomarkers (including total tau, neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and ubiquitin C-terminal hydrolase-L1 (UCH-L1)) and white-matter neuroimaging biomarkers in collegiate athletes with sport-related concussion (SRC) from 24-hours post-injury to 1 week after return-to-play. <br><br>METHODS: We analyze clinical and imaging data of concussed collegiate athletes in the Concussion Assessment, Research and Education (CARE) Consortium. The CARE participants completed same-day clinical assessments, blood draws, and diffusion tensor imaging (DTI) at 3 time points: 24-48 hours post-injury, point of becoming asymptomatic, and 7 days following return-to-play. DTI probabilistic tractography was performed for each subject at each time point to render 27 subject-specific major white-matter tracts. The microstructural organization of these tracts was characterized by four DTI metrics. Mixed-effects models with random intercepts were applied to test whether white-matter microstructural abnormalities are associated with the blood-based biomarkers at the same time point. An interaction model was used to test if the association varies across time points. A lagged model was used to test if early blood-based biomarkers predict later microstructural changes. <br><br>RESULTS: Data from 77 collegiate athletes were included in the following analyses. Among the 4 blood-based biomarkers, total tau had significant associations with the DTI metrics across the 3 time points. In particular, tau was positively associated with radial diffusivity (RD) in the right corticospinal tract (β=0.25, SE=0.07, p (FDR-adjusted) =0.016) and superior thalamic radiation (β=0.21, SE=0.07, p (FDR-adjusted) =0.042). NfL and GFAP had time-dependent associations with the DTI metrics. NfL showed significant associations only at the asymptomatic time point (|β|s>0.12, SEs<0.09, ps (FDR-adjusted) <0.05) and GFAP showed a significant association only at 7-days following return-to-play (βs>0.14, SEs<0.06, ps (FDR-adjusted) <0.05). The p-values for the associations of early tau and later RD were not significant after multiple comparison adjustment, but were less than 0.1 in seven white-matter tracts. <br><br>CONCLUSIONS: This prospective study using data from the CARE Consortium demonstrated that in the early phase of SRC, white-matter microstructural integrity detected by DTI neuroimaging was associated with elevated levels of blood-based biomarkers of traumatic brain injury. Total tau in the blood showed the strongest association with white-matter microstructural changes.<p />  <p>Language: en</p>
LA  - en
SN  - 0028-3878
UR  - http://dx.doi.org/10.1212/WNL.0000000000207389
ID  - ref1
ER  -