History of traumatic brain injury is associated with impaired cognition and imaging evidence of altered white matter tract integrity in UK Biobank (n=47,920)

Background: Traumatic brain injury (TBI) is a recognized risk factor for neurodegenerative disease (NDD). Nevertheless, currently we have no means to identify patients most at risk of NDD following TBI and, as a result, no means to target risk mitigation interventions. To address this, we tested for associations between TBI, cognitive performance and imaging measures of white matter integrity in UK Biobank (UKB) participants. Method: From the UKB imaging sub-study (n=47,920), participants were identified with either self-reported (n=177) or ICD-10 coded broad- (head injury codes; n=822) or narrow-band (TBI specific codes; n=239) TBI, or as controls with no relevant history of injury (n=47,098). Cognitive scores and magnetic resonance imaging (MRI) measures of white matter integrity were then compared between TBI and non-TBI participants, with results corrected for age at assessment, sex, deprivation, and cardiometabolic/exogenous hormone medications. Results: Whether based on self-reported history or ICD-10 coding, participants with TBI demonstrated poorer cognitive scores and multiple MRI measures of disturbance in corpus callosum integrity compared to participants with no TBI history. The strongest deleterious associations were for narrow-band TBI, with standardized betas around 0.2-0.3 difference (all P<0.01) for the majority of phenotypes. All cognitive and imaging phenotypes were strongly inter-correlated (P<0.001), with no evidence of sex-specific effects. Conclusion: This large, general population cohort study provides evidence of impairment in cognitive performance and correlated MRI measures of white matter integrity in individuals with history of TBI. These observations may provide a means to identify patients most at risk of NDD following TBI to which mitigation strategies might be targeted.