Breton M Asken1, Russell M Bauer2, Steven T DeKosky2, Zachary M Houck2, Charles C Moreno2, Michael S Jaffee2, Arthur G Weber2, James R Clugston2. 1. From the Departments of Clinical and Health Psychology (B.M.A., R.M.B., Z.M.H., C.C.M.), Neurology (R.M.B., S.T.D., M.S.J., J.R.C.), and Community Health and Family Medicine (J.R.C.), and University Athletic Association (J.R.C.), University of Florida, Gainesville; and Banyan Biomarkers, Inc. (A.G.W.), Alachua, FL. basken8@phhp.ufl.edu. 2. From the Departments of Clinical and Health Psychology (B.M.A., R.M.B., Z.M.H., C.C.M.), Neurology (R.M.B., S.T.D., M.S.J., J.R.C.), and Community Health and Family Medicine (J.R.C.), and University Athletic Association (J.R.C.), University of Florida, Gainesville; and Banyan Biomarkers, Inc. (A.G.W.), Alachua, FL.
Abstract
OBJECTIVE: To describe variability in concussion biomarker concentrations collected from serum in a sample of healthy collegiate athletes, as well as report reliability metrics in a subsample of female athletes. 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 (CNPase) 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. Standardized normative distributions are reported for each biomarker. We evaluated main effects (analyses of variance) of sex and race, reporting demographic-specific normative metrics when appropriate. In a subset of 31 female participants, test-retest reliability (Pearson r) and reliable change indices (80%, 90%, and 95% confidence intervals) across a 6- to 12-month interval are reported for Aβ42, total tau, S100B, and UCH-L1. RESULTS: Males exhibited higher UCH-L1 (p < 0.001, Cohen d = 0.75) and S100B (p < 0.001, d = 0.56) than females, while females had higher CNPase (p < 0.001, d = 0.43). Regarding race, black participants had higher baseline levels of UCH-L1 (p < 0.001, d = 0.61) and S100B (p < 0.001, d = 1.1) than white participants. Conversely, white participants had higher baseline levels of Aβ42 (p = 0.005, d = 0.28) and CNPase (p < 0.001, d = 0.46). Test-retest reliability was generally poor, ranging from -0.02 to 0.40, and Aβ42 significantly increased from time 1 to time 2. CONCLUSION: Healthy collegiate athletes express concussion-related serum biomarkers in variable concentrations. Accounting for demographic factors such as sex and race is essential. Evidence suggested poor reliability for serum biomarkers; however, understanding how other factors influence biomarker expression, as well as knowledge of reliable change metrics, may improve clinical interpretation and future study designs.
OBJECTIVE: To describe variability in concussion biomarker concentrations collected from serum in a sample of healthy collegiate athletes, as well as report reliability metrics in a subsample of female athletes. 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 (CNPase) 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. Standardized normative distributions are reported for each biomarker. We evaluated main effects (analyses of variance) of sex and race, reporting demographic-specific normative metrics when appropriate. In a subset of 31 female participants, test-retest reliability (Pearson r) and reliable change indices (80%, 90%, and 95% confidence intervals) across a 6- to 12-month interval are reported for Aβ42, total tau, S100B, and UCH-L1. RESULTS: Males exhibited higher UCH-L1 (p < 0.001, Cohen d = 0.75) and S100B (p < 0.001, d = 0.56) than females, while females had higher CNPase (p < 0.001, d = 0.43). Regarding race, black participants had higher baseline levels of UCH-L1 (p < 0.001, d = 0.61) and S100B (p < 0.001, d = 1.1) than white participants. Conversely, white participants had higher baseline levels of Aβ42 (p = 0.005, d = 0.28) and CNPase (p < 0.001, d = 0.46). Test-retest reliability was generally poor, ranging from -0.02 to 0.40, and Aβ42 significantly increased from time 1 to time 2. CONCLUSION: Healthy collegiate athletes express concussion-related serum biomarkers in variable concentrations. Accounting for demographic factors such as sex and race is essential. Evidence suggested poor reliability for serum biomarkers; however, understanding how other factors influence biomarker expression, as well as knowledge of reliable change metrics, may improve clinical interpretation and future study designs.
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