Research Reports - Risk of hospitalization with neurodegenerative disease after moderate-to-severe traumatic brain injury in the working-age population:

PLoS Med. 2017 Jul 5;14(7):e1002316. doi: 10.1371/journal.pmed.1002316.
eCollection 2017 Jul.

Raj R(1), Kaprio J(2)(3), Korja M(1), Mikkonen ED(4), Jousilahti P(5), Siironen
J(1).

BACKGROUND: 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.
METHODS AND FINDINGS: 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.
CONCLUSIONS: 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. 

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