Faculty Collaboration Database

Longitudinal Associations Between Blood Biomarkers and White Matter MRI in Sport-Related Concussion: A Study of the NCAA-DoD CARE Consortium. Neurology 2023 Jul 11;101(2):e189-e201

Date

06/17/2023

Pubmed ID

37328299

Pubmed Central ID

PMC10351550

DOI

10.1212/WNL.0000000000207389

Scopus ID

2-s2.0-85164284487 (requires institutional sign-in at Scopus site)   1 Citation

Abstract

BACKGROUND AND OBJECTIVES: 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) and white matter neuroimaging biomarkers in collegiate athletes with sport-related concussion (SRC) from 24 hours postinjury to 1 week after return to play.

METHODS: We analyzed 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 postinjury, point of becoming asymptomatic, and 7 days after return to play. DTI probabilistic tractography was performed for each participant at each time point to render 27 participant-specific major white matter tracts. The microstructural organization of these tracts was characterized by 4 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 whether the association varies across time points. A lagged model was used to test whether early blood-based biomarkers predict later microstructural changes.

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, high tau level was associated with high 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 after 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 7 white matter tracts.

DISCUSSION: 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.

Author List

Wu YC, Wen Q, Thukral R, Yang HC, Gill JM, Gao S, Lane KA, Meier TB, Riggen LD, Harezlak J, Giza CC, Goldman J, Guskiewicz KM, Mihalik JP, LaConte SM, Duma SM, Broglio SP, Saykin AJ, McAllister TW, McCrea MA

Authors

Michael McCrea PhD Professor in the Neurosurgery department at Medical College of Wisconsin
Timothy B. Meier PhD Associate Professor in the Neurosurgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Athletic Injuries
Biomarkers
Brain Concussion
Diffusion Tensor Imaging
Football
Humans
Prospective Studies
White Matter