Risk of hospitalization with neurodegenerative disease after moderate-to-severe traumatic brain injury in the working-age population: A retrospective cohort study using the Finnish national health registries

by Rahul Raj, Jaakko Kaprio, Miikka Korja, Era D. Mikkonen, Pekka Jousilahti, Jari Siironen

Previous epidemiological studies suggest that working-aged persons with a history of moderate-to-severe traumatic brain injury (TBI) may have an increased risk for developing neurodegenerative disease (NDD) while persons with a history of mild TBI do not. In this comprehensive nationwide study in Finland, we assessed the risk of NDD and history of moderate-to-severe TBI in the working-age population.

We performed a population-based follow-up study using the Finnish Care Register for Health Care to identify all persons between the ages of 18 and 65 years hospitalized during 1987–2014 due to TBI who did not have a baseline NDD diagnosis. We compared the risk of hospitalization with NDD between persons hospitalized due to moderate-to-severe TBI (intracranial lesions) and persons hospitalized due to mild TBI (no intracranial lesions). Follow-up NDD diagnoses were recorded from 1 year following the TBI to the end of 2014. NDD diagnoses included dementia, Parkinson disease, and amyotrophic lateral sclerosis. We used a Cox proportional hazards model, adjusting for age, sex, education, and socioeconomic group, to assess the association between TBI and NDD. In total, 19,936 and 20,703 persons with a history of moderate-to-severe TBI and mild TBI, respectively, were included. The overall time at risk was 453,079 person-years (median 10 years per person). In total, 3.5% (N = 696) persons in the moderate-to-severe TBI group developed NDD compared to 1.6% (N = 326) in the mild TBI group. After adjusting for covariates, moderate-to-severe TBI was associated with an increased risk for NDD, with a hazard ratio (HR) of 1.8 (95% CI 1.6–2.1) compared to mild TBI. Of the NDD subtypes, only moderate-to-severe TBI was associated with an increased risk for dementia (HR 1.9, 95% CI 1.6–2.2). Yet, this large-scale epidemiological study does not prove that there is a causal relationship between moderate-to-severe TBI and NDD. Further, the Care Register for Health Care includes only hospitalized persons; thus, patients diagnosed with NDD in the outpatient setting may have been missed. Additional limitations include the potential for miscoding and unmeasured confounds.

In working-aged persons, a history of moderate-to-severe TBI is associated with an increased risk for future dementia but not for Parkinson disease or amyotrophic lateral sclerosis.