Abstract
INTRODUCTION: We investigated the association between traumatic brain injury (TBI) and incidence of early-onset dementia (EOD) versus late-onset dementia (LOD). METHODS: We included 501,710 UK Biobank participants (average age 56.5). Over a median 13.6 years of follow-up, 836 developed EOD (before 65) and 8947 developed LOD (after 65). We estimated hazard ratios (HRs) for TBI's association with EOD and LOD using Cox proportional hazard models with TBI as a time-varying exposure and coefficient. RESULTS: TBI was associated with higher risk of both EOD (HR: 4.06 [95% confidence interval: 3.13, 5.26]) and LOD (HR: 2.51 [2.31, 2.72]. Among participants included in both EOD and LOD analyses, the effect estimate was higher for EOD (3.41 vs. 2.80), but the difference was not statistically significant. The association of TBI with EOD was stronger in those with more severe TBIs. DISCUSSION: TBI is associated with an increased risk of EOD, with a higher risk observed in more severe injuries. HIGHLIGHTS: Traumatic brain injury (TBI) is a significant risk factor for early-onset dementia (EOD). TBI was analyzed as a time-varying exposure and time-varying coefficient. Moderate/severe/penetrating TBIs have a heightened risk of developing EOD. TBI is more strongly associated with an earlier age cut-off for dementia.