Reserves, Injury Severity, and Outcomes in Traumatic Brain Injury: A CENTER-TBI Observational Study.

OBJECTIVE: Reserve refers to the brain's ability to maintain function after an injury and strongly relates to traumatic brain injury (TBI) outcomes. This study examined (1) whether associations between pre-injury reserve proxies and outcomes differed across injury severity categories, and (2) whether the impact of injury severity varied across functional, symptomatic, and cognitive outcomes. METHODS: This observational cohort study used data from CENTER-TBI. Of 4509 enrolled patients, 3377 were between 18 and 75 years and alive 6 months post-injury. Outcomes included functional outcome (GOSE, n = 2790), self-reported symptoms (RPQ, n = 1470), and cognition (composite score, n = 1968). Pre-injury reserve proxies were education, age, and psychiatric history. Injury severity was categorized as uncomplicated mild TBI, complicated mild TBI, moderate, and severe TBI. RESULTS: Of nine tested interactions between reserve proxies and injury severity, only the interaction of age with injury severity on cognition was significant (β = 0.1, p < 0.001), with age being less influential in severe TBI. Higher education and no psychiatric history predicted better outcomes across all severities. Younger age predicted more favorable GOSE and cognitive scores. RPQ symptoms peaked among adults aged 46-60. Increasing injury severity was associated with progressively lower odds of GOSE ≥ 6. RPQ scores plateaued in moderate TBI. Cognitive performance was similar in uncomplicated and complicated mild TBI. INTERPRETATION: Pre-injury reserve proxies predicted outcome largely independent of injury severity, with higher reserves linked to better recovery. Injury severity showed a graded relationship with functional outcome. Symptom burden and cognitive impairment demonstrated non-linear patterns across severity categories. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT0221022.