Research Article: 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

Date Published: July 5, 2017

Publisher: Public Library of Science

Author(s): Rahul Raj, Jaakko Kaprio, Miikka Korja, Era D. Mikkonen, Pekka Jousilahti, Jari Siironen, Karim Brohi

Abstract: BackgroundPrevious 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.Methods and findingsWe 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.ConclusionsIn 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.

Partial Text: Traumatic brain injury (TBI) is a globally increasing healthcare problem, affecting persons of all ages [1]. Following the early phases of TBI, patients face a significant risk of long-term disability and neurological morbidity [2]. Previous epidemiological studies have found an association between history of TBI and risk for future neurodegenerative disease (NDD) (a concept including dementia, Parkinson disease [PD], and amyotrophic lateral sclerosis [ALS]), but the results have been conflicting and few studies have focused on the working-age population [3–7]. Gardner et al. showed that persons under 65 years with a history of mild TBI did not have an increased risk for dementia compared to non-TBI controls [8]. The development of NDD is supposedly most deleterious in the working-age population, as this not only causes significant morbidity but also has major socioeconomic consequences. Yet, to our knowledge, no previous studies have specifically looked at the overall risk for developing NDD in working-aged persons hospitalized due to TBI.

In this nationwide study in Finland investigating the association between TBI and NDD, we found that persons with a history of moderate-to-severe TBI had an 80% increased probability of future NDD compared to persons with a history of mild TBI. The matched sample analysis strengthened our results. The risk of future NDD increased with TBI severity (length of hospital stay) in a dose–response pattern. However, when the three NDD subtypes were analyzed separately, TBI was associated with increased risk only for dementia (90% increased probability).



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