Age-Related Differences in Diagnostic Accuracy of Plasma Glial Fibrillary Acidic Protein and Tau for Identifying Acute Intracranial Trauma on Computed Tomography

A TRACK-TBI Study

Raquel C. Gardner, Richard Rubenstein, Kevin K.W. Wang, Frederick Korley, John K. Yue, Esther L. Yuh, Pratik Mukherje, Alex B. Valadka, David O. Okonkwo, Ramon Diaz-Arrastia, Geoffrey T. Manley

Research output: Contribution to journalArticle

Abstract

Plasma tau and glial fibrillary acidic protein (GFAP) are promising biomarkers for identifying traumatic brain injury (TBI) patients with intracranial trauma on computed tomography (CT). Accuracy in older adults with mild TBI (mTBI), the fastest growing TBI population, is unknown. Our aim was to assess for age-related differences in diagnostic accuracy of plasma tau and GFAP for identifying intracranial trauma on CT. Samples from 169 patients (age <40 years [n = 79], age 40-59 years [n = 60], age 60 years+ [n = 30]), a subset of patients from the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) Pilot study who presented with mTBI (Glasgow Coma Scale score of 13-15), received head CT, and consented to blood draw within 24 h of injury, were assayed for hyperphosphorylated-tau (P-tau), total-tau (T-tau; both via amplification-linked enhanced immunoassay using multi-arrayed fiberoptics), and GFAP (via sandwich enzyme-linked immunosorbent assay). P-tau, T-tau, P-tau:T-tau ratio, and GFAP concentration were significantly associated with CT findings. Overall, discriminative ability declined with increasing age for all assays, but this decline was only statistically significant for GFAP (area under the receiver operating characteristic curve [AUC]: old 0.73 [reference group; ref] vs. young 0.93 [p = 0.037] or middle-aged 0.92 [p = 0.0497]). P-tau concentration consistently showed the highest diagnostic accuracy across all age-groups (AUC: old 0.84 [ref] vs. young 0.95 [p = 0.274] or middle-aged 0.93 [p = 0.367]). Comparison of models including P-tau alone versus P-tau plus GFAP revealed significant added value of GFAP. In conclusion, the GFAP assay was less accurate for identifying intracranial trauma on CT among older versus younger mTBI patients. Mechanisms of this age-related difference, including role of assay methodology, specific TBI neuroanatomy, pre-existing conditions, and anti-thrombotic use, warrant further study.

Original languageEnglish (US)
Pages (from-to)2341-2350
Number of pages10
JournalJournal of Neurotrauma
Volume35
Issue number20
DOIs
StatePublished - Oct 15 2018
Externally publishedYes

Fingerprint

Glial Fibrillary Acidic Protein
Blood Proteins
Tomography
Wounds and Injuries
Research
Area Under Curve
Brain Concussion
Neuroanatomy
Glasgow Coma Scale
Preexisting Condition Coverage
Immunoassay
ROC Curve
Age Groups
Biomarkers
Enzyme-Linked Immunosorbent Assay
Head
Traumatic Brain Injury
Population

Keywords

  • Biomarkers
  • CT
  • Geriatric
  • Traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Age-Related Differences in Diagnostic Accuracy of Plasma Glial Fibrillary Acidic Protein and Tau for Identifying Acute Intracranial Trauma on Computed Tomography : A TRACK-TBI Study. / Gardner, Raquel C.; Rubenstein, Richard; Wang, Kevin K.W.; Korley, Frederick; Yue, John K.; Yuh, Esther L.; Mukherje, Pratik; Valadka, Alex B.; Okonkwo, David O.; Diaz-Arrastia, Ramon; Manley, Geoffrey T.

In: Journal of Neurotrauma, Vol. 35, No. 20, 15.10.2018, p. 2341-2350.

Research output: Contribution to journalArticle

Gardner, RC, Rubenstein, R, Wang, KKW, Korley, F, Yue, JK, Yuh, EL, Mukherje, P, Valadka, AB, Okonkwo, DO, Diaz-Arrastia, R & Manley, GT 2018, 'Age-Related Differences in Diagnostic Accuracy of Plasma Glial Fibrillary Acidic Protein and Tau for Identifying Acute Intracranial Trauma on Computed Tomography: A TRACK-TBI Study', Journal of Neurotrauma, vol. 35, no. 20, pp. 2341-2350. https://doi.org/10.1089/neu.2018.5694
Gardner, Raquel C. ; Rubenstein, Richard ; Wang, Kevin K.W. ; Korley, Frederick ; Yue, John K. ; Yuh, Esther L. ; Mukherje, Pratik ; Valadka, Alex B. ; Okonkwo, David O. ; Diaz-Arrastia, Ramon ; Manley, Geoffrey T. / Age-Related Differences in Diagnostic Accuracy of Plasma Glial Fibrillary Acidic Protein and Tau for Identifying Acute Intracranial Trauma on Computed Tomography : A TRACK-TBI Study. In: Journal of Neurotrauma. 2018 ; Vol. 35, No. 20. pp. 2341-2350.
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