Accelerated brain aging with functional and cognitive decline after traumatic brain injury

Introduction Individuals with a history of traumatic brain injury (TBI) have been shown to have greater brain age compared to their chronological age. However, the trajectory of post-TBI brain aging and its association with long-term functional and cognitive outcomes remain unclear. This report aims to characterize the influence of brain aging on functional outcomes post-TBI. Methods Data were drawn from 157 individuals enrolled in the Magnetic Resonance Imaging of NeuroTrauma Study cohort. Participants completed self-report assessments and underwent structural neuroimaging (T1-weighted magnetic resonance imaging at baseline and at 1-, 6-, and 18- months). Brain age was estimated using a neural network trained on T1 scans, and the predicted age difference (PAD) was calculated. Functional outcomes were assessed using the Glasgow Outcome Scale Extended (GOSE) and the Mini-Mental State Examination (MMSE). Logistic mixed-effects models examined associations between PAD and outcomes. Results The predicted brain age estimates derived from the T1 scans were higher than the post-TBI participants’ chronological ages. Logistic mixed-effects models showed a 16% increase in the odds of unfavorable functional recovery (GOSE ≤ 4) and a 6% increase in the odds of cognitive impairment (MMSE ≤ 28) per unit increase in PAD. Conclusion Individuals with TBI exhibit functional and cognitive declines that correlate with increased brain age. An elevated PAD is associated with poorer outcomes and may serve as a clinically useful biomarker. Incorporating brain age metrics into care may support early detection, guide personalized interventions, and improve outcomes. Future research should explore how brain age interacts with other risk factors to better understand post-TBI decline.