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. 2024 Dec 2;7(12):e2450499.
doi: 10.1001/jamanetworkopen.2024.50499.

Traumatic Brain Injury and Risk of Incident Comorbidities

Cathra Halabi  1   2 , Saef Izzy  3   4   5 , Anthony M DiGiorgio  6   7 , Hunter Mills  8 , Farid Radmanesh  9 , John K Yue  6 , Habibeh Ashouri Choshali  8 , Gundolf Schenk  8 , Sharat Israni  8 , Ross Zafonte  4   5   10   11 , Geoffrey T Manley  2   6
Affiliations

Traumatic Brain Injury and Risk of Incident Comorbidities

Cathra Halabi et al. JAMA Netw Open. .

Abstract

Importance: Traumatic brain injury (TBI) is associated with chronic medical conditions. Evidence from diverse clinical administrative datasets may improve care delivery.

Objective: To 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 participants: In 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.

Exposure: TBI.

Main outcomes and measures: International 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.

Results: The 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 relevance: In 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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Halabi reported receiving grants from the Pac-12 Student-Health and Well-Being Initiative, Weill Institute for Neurosciences Neurohub, UC Noyce Initiative, and National Institute on Deafness and Other Communication Disorders outside the submitted work. Dr DiGiorgio reported receiving grants from the Charles Koch Foundation, Mercatus Center at George Mason University, and DePuy Synthes outside the submitted work. Dr Yue reported receiving grants from the Neurosurgery Research and Education Foundation, awarded to the University of California, San Francisco (funding period July 1, 2022, to June 30, 2023) outside the submitted work. Dr Schenk reported receiving grants from the US Department of Defense (DoD) during the conduct of the study and having a patent for the US Patent and Trademark Office issued to the Regents of the University of California. Dr Zafonte reported serving on the scientific advisory board of Myomo and Kisbee and the National Football League (NFL) Players Association Mackey-White committee; advising Nanodx; receiving textbook royalties from Springer; receiving funding from the National Institute on Disability, Independent Living, and Rehabilitation Research, US DoD, and National Institutes of Health (NIH); and serving as the principal investigator of the football players health study at Harvard University. Dr Manley reported receiving grants from the US DoD, NIH, and NFL during the conduct of the study and funding from NeuroTrauma Sciences LLC and One Mind outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Study Flowchart
There were more patients with mild traumatic brain injury (TBI) than those with moderate to severe TBI. Matching was done first for mild TBI and moderate to severe TBI in a 1:1 manner; then, these groups were matched to unexposed patients (control group). Matching occurred after patients with preexisting comorbidities of interest were excluded. A total of 59 223 patients were excluded because they had no prior encounters, 61 116 patients because they had no follow-up, and 63 103 because they had no prior nor follow-up encounters.
Figure 2.
Figure 2.. Risk of Comorbidities, Original Model
HR indicates hazard ratio; mTBI, mild traumatic brain injury; msTBI, moderate to severe traumatic brain injury; TIA, transient ischemic attack; whiskers, 95% CIs.
Figure 3.
Figure 3.. Select Kaplan-Meier Curves
Longitudinal risk of select incident conditions is presented. mTBI indicates mild traumatic brain injury; msTBI, moderate to severe traumatic brain injury.
See this image and copyright information in PMC

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