Temporal Profile of Serum Neurofilament Light (NF-L) and Heavy (pNF-H) Level Associations With 6-Month Cognitive Performance in Patients With Moderate-Severe Traumatic Brain Injury

Abstract

Objective: Identification of biomarkers of cognitive recovery after traumatic brain injury (TBI) will inform care and improve outcomes. This study assessed the utility of neurofilament (NF-L and pNF-H), a marker of neuronal injury, informing cognitive performance following moderate-to-severe TBI (msTBI). Setting: Level 1 trauma center and outpatient via postdischarge follow-up. Participants: N = 94. Inclusion criteria: Glasgow Coma Scale score less than 13 or 13-15 with clinical evidence of moderate-to-severe injury traumatic brain injury on clinical imaging. Exclusion criteria: neurodegenerative condition, brain death within 3 days after injury. Design: Prospective observational study. Blood samples were collected at several time points post-injury. Cognitive testing was completed at 6 months post-injury. Main Measures: Serum NF-L (Human Neurology 4-Plex B) pNF-H (SR-X) as measured by SIMOA Quanterix assay. Divided into 3 categorical time points at days post-injury (DPI): 0-15 DPI, 16-90 DPI, and >90 DPI. Cognitive composite comprised executive functioning measures derived from 3 standardized neuropsychological tests (eg, Delis-Kaplan Executive Function System: Verbal Fluency, California Verbal Learning Test, Second Edition, Wechsler Adult Intelligence Scale, Third Edition). Results: pNF-H at 16-90 DPI was associated with cognitive outcomes including a cognitive-executive composite score at 6 months (β = −.430, t 34 = −3.190, P = .003). Conclusions: Results suggest that “subacute” elevation of serum pNF-H levels may be associated with protracted/poor cognitive recovery from msTBI and may be a target for intervention. Interpretation is limited by small sample size and including only those who were able to complete cognitive testing.