Traumatic Brain Injury and Risk of Incident Comorbidities
Authors: Halabi Cathra , Izzy Saef , DiGiorgio Anthony M. , Mills Hunter , Radmanesh Farid , Yue John K. , Ashouri Choshali Habibeh , Schenk Gundolf , Israni Sharat , Zafonte Ross , Manley Geoffrey T. 
Published: December 2024

ImportanceTraumatic brain injury (TBI) is associated with chronic medical conditions. Evidence from diverse clinical administrative datasets may improve care delivery.ObjectiveTo characterize post-TBI risk of incident neuropsychiatric and medical conditions in a California health care system administrative database and validate findings from a Massachusetts dataset.Design, Setting, and ParticipantsIn this cohort study, prospective longitudinal cohorts using data from 5 University of California health care settings between 2013 and 2022 were studied. Patients aged 18 years and older with mild (mTBI) or moderate to severe TBI (msTBI) were included. Unexposed individuals were propensity matched by age, race and ethnicity, sex, University of California site, insurance coverage, area deprivation index (ADI) score, and duration from index date to most recent clinical encounter. Patients with study comorbidities of interest before the index date were excluded. Data were analyzed August to October 2024.ExposureTBI.Main Outcomes and MeasuresInternational Classification of Diseases, Ninth Revision (ICD-9) and International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes were used to identify patients with TBI and patients with up to 22 comorbidities within neurological, psychiatric, cardiovascular, and endocrine umbrella groupings. Cox proportional hazard models were used to generate yearly hazard ratios (HRs) from 6 months up to 10 years after a TBI. Models were further stratified by age and ADI score.ResultsThe study consisted of 20 400 patients (9264 female [45.4%]; 1576 Black [7.7%], 3944 Latinx [19.3%], and 10 480 White [51.4%]), including 5100 patients with mTBI (median [IQR] age, 36.0 [25.0-51.0] years), 5100 patients with msTBI (median [IQR age, 35.0 [25.0-52.0] years), and 10 200 matched patients in the control group (median [IQR] age, 36.0 [25.0-51.0] years). By ADI score quintile, there were 2757 unexposed patients (27.0%), 1561 patients with mTBI (30.6%), and 1550 patients with msTBI (30.4%) in the lowest (1-2) quintiles and 1523 unexposed patients (14.9%), 769 patients with mTBI (15.1%), and 804 patients with msTBI (15.8%) in the highest quintiles (9-10). TBI of any severity was associated with increased risk of nearly all conditions (mTBI HRs ranged from 1.30; 95% CI, 1.07-1.57 for hypothyroidism to 4.06; 95% CI, 3.06-5.39 for dementia, and msTBI HRs ranged from 1.35; 95% CI, 1.12-1.62 for hypothyroidism to 3.45; 95% CI, 2.73-4.35 for seizure disorder). Separate age and ADI stratifications revealed patient populations at increased risk, including middle-age adults (ages 41-60 years), with increased risk of suicidality (mTBI: HR, 4.84; 95% CI, 3.01-7.78; msTBI: HR, 4.08; 95% CI, 2.51-6.62). Suicidality risk persisted for patients with mTBI in the high ADI subgroup (HR, 2.23; 95% CI, 1.36-3.66).Conclusions and RelevanceIn this cohort study, TBI was a risk factor associated with treatable incident neuropsychiatric and other medical conditions, validating similar findings from a Massachusetts dataset. Additional exploratory findings suggested varying demographic and regional risk patterns, which may generate causal hypotheses for further research and inform clinical surveillance strategies.