Timing of neurorehabilitation and subsequent Alzheimer's disease risk in patients with moderate to severe traumatic brain injury: A nationwide retrospective cohort study in the United States

BackgroundTraumatic brain injury (TBI) is associated with an increased risk of Alzheimer's disease (AD). It is unknown if prompt neuro-rehabilitative treatment following moderate or severe TBI mitigates this risk compared with delayed treatment.ObjectiveTo determine whether immediate neuro-rehabilitative treatment following moderate or severe TBI reduces the risk of AD and related cognitive outcomes compared with delayed treatment.MethodsWe conducted a retrospective cohort using the TriNetX Analytics Platform, which includes health records from over 100 million US patients. Adults aged 50-90 years with moderate or severe TBI were included if they received immediate treatment (within 1 week) or delayed treatment (>1 week). Outcomes were AD risk at 3- and 5-year follow-up, with additional outcomes of mild cognitive impairment (MCI), dementia, and AD-related medication prescriptions. Cox proportional hazards models were applied to propensity score-matched cohorts, and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated.ResultsOf 37,081 eligible patients, 17,636 remained after propensity score matching. Immediate treatment was associated with lower AD risk compared with delayed treatment (HR, 0.59; 95% CI, 0.41-0.86 at 3 years; HR, 0.70; 95% CI, 0.52-0.94 at 5 years). Similar risk reductions were observed for MCI, dementia, and AD-related medication use.ConclusionsImmediate treatment following moderate or severe TBI was associated with significantly reduced risk of AD and related cognitive decline. These findings suggest that prompt intervention may mitigate long-term neurodegenerative consequences of TBI.