Concussion BASICS II: Baseline serum biomarkers, head impact exposure, and clinical measures

Abstract

Objective: To examine the effect of concussion history and cumulative exposure to collision sports on baseline serum biomarker concentrations, as well as associations between biomarker concentrations and clinical assessments.

Methods: In this observational cohort study, β-amyloid peptide 42 (Aβ₄₂), total tau, S100 calcium binding protein B (S100B), ubiquitin carboxy-terminal hydrolyzing enzyme L1 (UCH-L1), glial fibrillary acidic protein, microtubule associated protein 2, and 2',3'-cyclic-nucleotide 3'-phosphodiesterase serum concentrations were measured in 415 (61% male, 40% white, aged 19.0 ± 1.2 years) nonconcussed collegiate athletes without recent exposure to head impacts. Regression analyses were used to evaluate the relationship between self-reported history of concussion(s), cumulative years playing collision sports, clinical assessments, and baseline biomarker concentrations. Football-specific analyses were performed using a modified Cumulative Head Impact Index. Clinical assessments included symptom, cognitive, balance, and oculomotor tests.

Results: Athletes with a greater number of concussions had a higher baseline Aβ₄₂ concentration only (ρ = 0.140, p = 0.005, small effect size). No biomarker concentrations correlated with cumulative exposure to collision sports. Race status fully mediated the correlations of S100B, UCH-L1, and Aβ₄₂ with cognitive scores. Football exposure, specifically, was not associated with serum biomarker concentrations or clinical assessment scores based on the modified Cumulative Head Impact Index.

Conclusion: Concussion-related serum biomarkers showed no consistent association with concussion history, cumulative exposure to collision sports, or clinical assessments in a sample of healthy collegiate athletes. Serum Aβ₄₂ concentrations could increase following multiple previous concussions. Considering race status is essential when investigating links between biomarkers and cognition. The biomarkers studied may not detect residual effects of concussion or repetitive head impact exposure in otherwise asymptomatic collegiate athletes without recent exposure to head impacts. Much more research is needed for identifying reliable and valid blood biomarkers of brain trauma history.

Figure 1. Relationship between number of previous concussions and baseline serum biomarker concentrations

A significant but weak association was found between more previous concussions and higher baseline Aβ₄₂ levels (A). No other significant correlations were noted (B–G). Aβ₄₂ = β-amyloid peptide 42; CNPase = 2′,3′-cyclic-nucleotide 3′-phosphodiesterase; GFAP = glial fibrillary acidic protein; MAP2 = microtubule associated protein 2; S100B = S100 calcium binding protein B; SRC = sport-related concussion; UCH-L1 = ubiquitin carboxy-terminal hydrolyzing enzyme L1.

Figure 2. Relationship between cumulative exposure to collision sports and baseline serum biomarker concentrations

No significant correlations were noted for any biomarker (A–G). Aβ₄₂ = β-amyloid peptide 42; CNPase = 2′,3′-cyclic-nucleotide 3′-phosphodiesterase; GFAP = glial fibrillary acidic protein; MAP2 = microtubule associated protein 2; S100B = S100 calcium binding protein B; UCH-L1 = ubiquitin carboxy-terminal hydrolyzing enzyme L1.

Figure 3. Relationships between race, S100B, and cognitive measures

(A) S100B and race both significantly correlated with Verbal Memory, Visual Motor Speed, and Reaction Time. (B) Evidence of mediation: S100B and race significantly correlated. Controlling for race, the associations between S100B and Verbal Memory, Visual Motor Speed, and Reaction Time all became nonsignificant. Race remained significantly correlated with all composite scores while controlling for S100B effects. Numerical values represent regression weights (r or β). *p < 0.01, **p < 0.001. S100B = S100 calcium binding protein B.