Mild Traumatic Brain Injury Diagnosis Gets Biomarker Boost

PLASMA biomarkers may improve mild traumatic brain injury diagnosis in older adults when symptoms and imaging are unclear.

Objective blood based measures could help clinicians identify mild traumatic brain injury in older adults, a population in whom diagnosis is often complicated by nonspecific symptoms, preexisting cognitive changes, polypharmacy, and overlapping neurologic conditions.

In a cross sectional study of 89 adults aged 60–84 years, researchers evaluated the diagnostic accuracy of four plasma biomarkers: glial fibrillary acidic protein, or GFAP; ubiquitin C terminal hydrolase L1; brain derived tau; and neurofilament light. Participants included 35 healthy controls, 45 patients with diagnosed mild traumatic brain injury, and 9 patients with suspected mild traumatic brain injury after presentation to a tertiary adult trauma center within 72 hours of injury.

GFAP Offers Strongest Mild Traumatic Brain Injury Signal

All four biomarkers were significantly elevated in patients with diagnosed mild traumatic brain injury compared with controls after adjustment for age and biological sex. GFAP showed the strongest diagnostic performance, with an age and sex adjusted area under the curve of 0.93, indicating excellent accuracy. Brain derived tau showed good accuracy, with an adjusted area under the curve of 0.72, while neurofilament light and ubiquitin C terminal hydrolase L1 showed fair accuracy.

GFAP also remained robust across clinically relevant subgroups. Diagnostic performance was consistent when blood was collected within 24 hours of injury and at 24 hours or later. In patients with negative CT findings for mild traumatic brain injury, GFAP retained high accuracy, supporting its potential value when imaging does not show radiographic abnormalities.

Personalized Thresholds May Reduce Diagnostic Uncertainty

A key finding was that optimal biomarker thresholds varied by age and sex. GFAP thresholds rose from approximately 94–108 pg/mL at age 60 years to 194–208 pg/mL at age 84 years, while neurofilament light thresholds more than doubled across the same age range. Ubiquitin C terminal hydrolase L1 showed the clearest sex difference, with higher cutoffs for females than males.

These findings suggest that fixed biomarker thresholds could misclassify older adults. Age and sex adjusted interpretation may be essential for clinical use, particularly in emergency department settings where symptoms may be subjective or confounded.

Among patients with suspected mild traumatic brain injury, GFAP and brain derived tau were significantly elevated compared with controls. When personalized cutoffs were applied, 67% exceeded the GFAP threshold and 89% exceeded the brain derived tau threshold, providing objective evidence consistent with brain injury in diagnostically ambiguous cases.

The study was limited by its small suspected mild traumatic brain injury group, single center design, predominantly White cohort, and use of healthy controls rather than symptomatic emergency department comparators. Larger multicenter studies are needed to validate thresholds and assess prognostic value.

Reference

Spitz G et al. Diagnostic accuracy of plasma biomarkers for mild traumatic brain injury in older adults. JAMA Netw Open. 2026;9(5):e2615678.

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