Predictive Performance of Traumatic Brain Injury Biomarkers in High-Risk Elderly Patients

J Appl Lab Med. 2020 Jan 1;5(1):91-100. doi: 10.1093/jalm.2019.031393.


Background: Serum glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal esterase L1 (UCH-L1) have recently received US Food and Drug Administration approval for prediction of abnormal computed tomography (CT) in mild traumatic brain injury patients (mTBI). However, their performance in elderly patients has not been characterized.

Methods: We performed a posthoc analysis using the A Prospective Clinical Evaluation of Biomarkers of Traumatic Brain Injury (ALERT-TBI) study data. Previously recorded patient variables and serum values of GFAP and UCH-L1 from mTBI patients were partitioned at 65 years of age (herein referred to as ≥65, high-risk; <65, low-risk). We sought to assess the influence of age on predictive performance, sensitivity, and negative predictive value (NPV) of serum UCH-L1 and GFAP to predict intracranial injury by CT.

Results: Elderly mTBI patients constituted 25.7% of the patient cohort (n = 504/1959). Sensitivity and NPV of GFAP/UCH-L1 were 100%, with no significant difference from younger patients (P = 0.5525 and P > 0.9999, respectively). Specificity was significantly lower in elderly patients (0.131 vs 0.442; P < 0.0001) and decreased stepwise with older age. Compared to younger patients, elderly mTBI patients without abnormal (i.e., normal) CT findings also had a significantly higher GFAP (38.6 vs 16.2 pg/mL; P < 0.0001) and UCH-L1 (347.4 vs 232.1 pg/mL; P < 0.0001).

Conclusions: Sensitivity and NPV to predict intracranial injury by CT was nearly identical between younger and elderly mTBI patients. Decrements in specificity and increased serum values suggest that special deference may be warranted for elderly patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged, 80 and over
  • Biomarkers / blood
  • Brain / diagnostic imaging
  • Brain Concussion* / blood
  • Brain Concussion* / diagnosis
  • Correlation of Data
  • Female
  • Glial Fibrillary Acidic Protein / blood*
  • Humans
  • Male
  • Predictive Value of Tests
  • Risk Factors
  • Sensitivity and Specificity
  • Tomography, X-Ray Computed / methods*
  • Ubiquitin Thiolesterase / blood*


  • Biomarkers
  • GFAP protein, human
  • Glial Fibrillary Acidic Protein
  • Ubiquitin Thiolesterase