TY - JOUR
T1 - Age-Related Differences in Diagnostic Accuracy of Plasma Glial Fibrillary Acidic Protein and Tau for Identifying Acute Intracranial Trauma on Computed Tomography
T2 - A TRACK-TBI Study
AU - Gardner, Raquel C.
AU - Rubenstein, Richard
AU - Wang, Kevin K.W.
AU - Korley, Frederick K.
AU - Yue, John K.
AU - Yuh, Esther L.
AU - Mukherje, Pratik
AU - Valadka, Alex B.
AU - Okonkwo, David O.
AU - Diaz-Arrastia, Ramon
AU - Manley, Geoffrey T.
N1 - Funding Information:
This study was supported by the National Institutes of Neurological Disorders and Stroke (Beeson K23NS095755 to RCG, RC2 NS069409 to GTM, U01 NS086090 to GTM, and R21NS085455 to KWW), the American Federation for Aging Research (to RCG), the Department of Defense (DoD; W81XWH-13-1-0441 to GTM and W81XWH-14-2-0176 to GTM), the University of Florida McKnight Brain Institute BSCIRTF fund (to KWW), and the SUNY Downstate Medical Center (to RR). This study was also supported in part by the Office of the Assistant Secretary of Defense for Health Affairs through the DoD Broad Agency Announcement under award numbers W81XWH-11-2-0069 (RR) and W81XWH-14-2-0166 (RR).
Publisher Copyright:
© Copyright 2018, Mary Ann Liebert, Inc., publishers 2018.
PY - 2018/10/15
Y1 - 2018/10/15
N2 - 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.
AB - 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.
KW - Biomarkers
KW - CT
KW - Geriatric
KW - Traumatic brain injury
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U2 - 10.1089/neu.2018.5694
DO - 10.1089/neu.2018.5694
M3 - Article
C2 - 29717620
AN - SCOPUS:85054415691
SN - 0897-7151
VL - 35
SP - 2341
EP - 2350
JO - Central Nervous System Trauma
JF - Central Nervous System Trauma
IS - 20
ER -