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December 04, 2018; 91 (23) Article

Concussion BASICS II

Baseline serum biomarkers, head impact exposure, and clinical measures

Breton M. Asken, Russell M. Bauer, Steven T. DeKosky, Zachary M. Houck, Charles C. Moreno, Michael S. Jaffee, Dewayne N. Dubose, Jonathan K. Boone, Arthur G. Weber, James R. Clugston
First published November 7, 2018, DOI: https://doi.org/10.1212/WNL.0000000000006616
Breton M. Asken
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.K.B., D.N.D., J.R.C.), University of Florida, Gainesville; and Banyan Biomarkers, Inc. (A.G.W.), Alachua, FL.
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Russell M. Bauer
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.K.B., D.N.D., J.R.C.), University of Florida, Gainesville; and Banyan Biomarkers, Inc. (A.G.W.), Alachua, FL.
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Steven T. DeKosky
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.K.B., D.N.D., J.R.C.), University of Florida, Gainesville; and Banyan Biomarkers, Inc. (A.G.W.), Alachua, FL.
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Zachary M. Houck
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.K.B., D.N.D., J.R.C.), University of Florida, Gainesville; and Banyan Biomarkers, Inc. (A.G.W.), Alachua, FL.
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Charles C. Moreno
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.K.B., D.N.D., J.R.C.), University of Florida, Gainesville; and Banyan Biomarkers, Inc. (A.G.W.), Alachua, FL.
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Michael S. Jaffee
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.K.B., D.N.D., J.R.C.), University of Florida, Gainesville; and Banyan Biomarkers, Inc. (A.G.W.), Alachua, FL.
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Dewayne N. Dubose
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.K.B., D.N.D., J.R.C.), University of Florida, Gainesville; and Banyan Biomarkers, Inc. (A.G.W.), Alachua, FL.
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Jonathan K. Boone
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.K.B., D.N.D., J.R.C.), University of Florida, Gainesville; and Banyan Biomarkers, Inc. (A.G.W.), Alachua, FL.
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Arthur G. Weber
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.K.B., D.N.D., J.R.C.), University of Florida, Gainesville; and Banyan Biomarkers, Inc. (A.G.W.), Alachua, FL.
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James R. Clugston
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.K.B., D.N.D., J.R.C.), University of Florida, Gainesville; and Banyan Biomarkers, Inc. (A.G.W.), Alachua, FL.
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Citation
Concussion BASICS II
Baseline serum biomarkers, head impact exposure, and clinical measures
Breton M. Asken, Russell M. Bauer, Steven T. DeKosky, Zachary M. Houck, Charles C. Moreno, Michael S. Jaffee, Dewayne N. Dubose, Jonathan K. Boone, Arthur G. Weber, James R. Clugston
Neurology Dec 2018, 91 (23) e2123-e2132; DOI: 10.1212/WNL.0000000000006616

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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.

Glossary

Aβ42=
β-amyloid peptide 42;
BASICS=
Biomarkers Assessed in Collegiate Student-Athletes;
BESS=
Balance Error Scoring System;
CTE=
chronic traumatic encephalopathy;
GFAP=
glial fibrillary acidic protein;
ImPACT=
Immediate Postconcussion Assessment and Cognitive Testing;
K-D=
King-Devick;
mCHII=
modified Cumulative Head Impact Index;
NFL=
National Football League;
RHIE=
repetitive head impact exposure;
S100B=
S100 calcium binding protein B;
SAC=
Standardized Assessment of Concussion;
UCH-L1=
ubiquitin carboxy-terminal hydrolyzing enzyme L1

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Editorial page 1035

  • Articles page 1040

  • See page 1042

  • Received December 1, 2017.
  • Accepted in final form August 23, 2018.
  • © 2018 American Academy of Neurology
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