Restricted accessResearch articleFirst published online 2025-12
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
Traumatic 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.
Objective
To determine whether immediate neuro-rehabilitative treatment following moderate or severe TBI reduces the risk of AD and related cognitive outcomes compared with delayed treatment.
Methods
We 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.
Results
Of 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.
Conclusions
Immediate 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.
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