Acute traumatic brain injury (TBI) is associated with a decline in cognition involving one or more domains (learning and memory, language, executive function, complex attention, perceptual-motor, and social cognition) (1), and TBI-related symptoms may persist for more than 6 months post-injury (2). The economic impact of TBI on the United States Department of Veterans Affairs (VA) has been shown to extend over a decade (≥15 years) (3); however, TBI-related costs in the Department of Defense (DOD) or VA may even be underestimated compared with the civilian sector considering that service members and veterans face a higher risk of TBI within their lifetime (4) and are more likely to suffer from injury-related comorbidities, such as chronic pain, post-traumatic stress disorder (PTSD), and other mental health conditions (5–8). Up to 20% of more than 2.5 million deployed service members since 2003 are estimated to have sustained at least one TBI (9, 10). Comorbid mental health diagnosis, substance use disorders, general medical disorders, TBI, history of violent events, and suicide attempts increase the risk of post-injury recurrent hospitalizations and deaths (8).

Mild cognitive impairment prevalence in the US is 6.7% for ages 60–64 years, 8.4% for 65–69 years, and increases to 25.2% for 80–84 years (11). Dementia, a disease of older age, has an overall prevalence of 7.3% among the VA healthcare system users older than 65 years old (12). However, TBI is considered a risk factor for dementia diagnosis (13) and early onset dementia in veterans, defined as dementia onset in age less than 65 years (14). Veterans with comorbid TBI and dementia have a higher healthcare cost burden relative to TBI alone or those with no diagnosis, and older veterans with comorbid TBI and dementia have been shown to have higher annual total Veteran Health Administration (VHA) costs (3).

Individuals with TBI who suffer from chronic pain are at a higher risk of substance and/or opioid use disorder (OUD) (15), and the presence of a TBI history should be considered in clinical decision-making regarding the long-term use of opioids (16, 17). Approximately 23% of individuals with OUD appear to also use cannabis (18). Despite the lack of proven efficacy, cannabis is frequently used to self-treat a wide array of symptoms and conditions associated with post-TBI injury (e.g., chronic pain, headache, sleep disturbances, anxiety, and irritability) (19–21). Cannabis use disorder (CUD) presents as a problematic pattern of cannabis use, with either abuse or dependence, that results in clinically significant functional impairment or distress. Following the cannabis legalization process, similar to the general population, access to cannabis and cannabinoids has increased substantially among VA patients (22). The estimated prevalence of cannabis use in veterans increased from 9% in 2014 to nearly 12% in 2020 (23); however, its efficacy and safety profile remains uncertain (24, 25). While the antioxidant and anti-inflammatory properties of cannabidiol suggest protective effects of cannabis on dementia progression (26), dementia-like structural changes to the brain have also been observed in heavy, chronic cannabis users (27–31).

Dementia is a possible long-term comorbidity of TBI, potentially accelerated by the presence of chronic pain, and secondary substance and cannabis use may have a specific, critical role in the dementia process after TBI. All of these factors individually and in combination are likely to have overlapping and additive health effects that necessitate the availability and use of general and targeted VA healthcare resources. This study aimed to determine the VA healthcare costs associated with CUD and dementia diagnosis in veterans with TBI.

Compared with the No Dementia and No CUD group of veterans with confirmed TBI diagnosis, the highest annual total healthcare cost in VA and non-VA facilities was in veterans in the CUD only, which was associated with 1% less healthcare utilization. However, we observed the incidence rate of healthcare utilization in the dementia-related subgroups (Dementia only and Dementia and CUD groups) was 75% less than the No Dementia and No CUD group. Prior research has demonstrated that, compared with veterans without either TBI or dementia, veterans with TBI and dementia have the highest average annual costs of approximately USD$ 20,408, followed by the Dementia only (USD$ 4,822) and TBI only (USD$ 3,344) groups (3). Our findings suggest higher average healthcare costs in veterans with TBI and CUD compared with TBI and dementia. Cognitive dysfunction or impairment may reduce help-seeking intentions (45) and should be considered as a possible reason for lower dementia-related healthcare utilization. The significantly lower healthcare utilization without cost differences in veterans with a dementia diagnosis is consistent with higher dementia-related total costs that were found in long-term rehabilitation and domiciliary inpatient services (46). Despite the high prevalence and numerous associated adverse health consequences in individuals with CUD (47) and other individuals with substance use disorders (48, 49), other studies have found that veterans with CUD did not appear to seek treatment. In our study, compared with veterans with TBI but without dementia or CUD, veterans with TBI and CUD had the highest average annual healthcare costs, despite 1% lower healthcare utilization.

The timing of costs revealed the highest initial 5-year costs after TBI diagnosis were in the Dementia only group, which was driven by penetrating and moderate/severe TBI. Since the DoD healthcare costs were not included in our study, the immediate and expensive healthcare costs for penetrating and moderate/severe TBI are not reflected at the time of TBI. Other contributors to costs may include the persistence of TBI-related symptoms for more than 6 months post-injury (2) and the related needs of those veterans at high risk of various short- and long-term sequelae (50). Valuating the healthcare costs by subcategories in VA and non-VA facilities was beyond the focus of this study. However, relatively very high costs in the first 5 years (peak = $46,808 in year 4) could be explained by high-cost diagnostic tests, such as neuroimaging (51). The average time from TBI event to dementia diagnosis was 4.36 years for veterans in the dementia only group. Therefore, the highest initial in this group are less likely related to the prodromal phase of dementia where the veteran/family tries to find an answer to the cognitive difficulties, which needs further evaluation. While the burden of CUD costs is notable after 5 years following TBI, we did not observe extraordinary total healthcare costs in veterans with combined TBI, dementia, and CUD compared with those with dementia only in the first 5 years. These findings suggest that veterans with TBI and dementia only may be getting their healthcare needs met more quickly (i.e., in the first 5 years) while those with TBI, dementia, and CUD were not receiving sufficient initial care, resulting in higher healthcare costs after 5 years. Moreover, the absence of a high burden of healthcare costs in veterans with dementia and CUD in the short term (first 5 years) could be explained by the protective or regulatory effects of cannabis use (52, 53). The specific “causative” factors involved need further investigation, and it is possible that the antioxidant and anti-inflammatory properties of cannabidiol products (26) lead to a delay in seeking care in the first 5 years. Of note, after this initial period, costs of all types become much higher in those with dementia and CUD. Finally, dementia is a clinical diagnosis defined as at least two impaired mental functions that interfere with daily activities (54). Therefore, the documented dementia diagnosis may not represent all of the actual dementia cases. The sample sizes of veterans with TBI, CUD, and early onset dementia, diagnoses that have a high positive predictive value, were not large enough to replicate a sensitivity analysis from prior research (14). To overcome this limitation, we conducted a sensitivity analysis with confirmed dementia cases by identifying at least two dementia diagnoses. The sensitivity analysis only showed heterogeneity in the costs of dementia-related subgroups and warrants further evaluation.

This population-based study provides a broad view of the association of TBI, dementia, CUD, and VHA costs; however, as with any large database study, there were limitations. These results are limited to characteristics and conditions measured and stored in electronic health records (EHRs), which means that cannabis exposure information is limited to documented ICD codes in VA and DoD, which likely under-represents dosage and the chronicity of cannabis exposure. Of note, the EHR system in VHA allowed the inclusion of reliable study measures, such as the frequency of CUD and identification of the TBI index date relative to the documented development of CUD, strengthening our assessment of the associations between CUD, TBI, and dementia. While there are adequate techniques available to account for potential structural population differences in comorbidities and other expenditure-related factors to establish a proper cause-and-effect relationship (55), our study primarily relied on controlling for all measured covariates to focus on the excess burden of CUD in total healthcare costs and trajectories after TBI, providing a broader perspective on CUD costs for VHA. Nevertheless, in Supplementary Table S2, we provide an estimate of the potential extent of structural population differences based on dementia and CUD status. The ascertainment of the timing of TBI is problematic in our cohort and based on only the first time that a TBI diagnosis is noted in VA medical records. There is limited information on events such as lifetime TBI history and other variables such as type of brain injury (diffuse vs. focal), repetitive exposures, and mechanism of injury. Thus, TBIs reported here are not necessarily representative of service-connected injury (i.e., from deployed settings and/or related to military service) alone but may also include TBIs that occurred from a range of causes after leaving DoD (e.g., motor vehicle crashes, sports injuries, assault, and falls). While LIMBIC-CENC has engaged in an extensive effort to overcome this limitation and provide reliable TBI-related information, there are always certain limitations to Big Data analyses (i.e., optimization and empowerment of the data by aggregating information from different sources such as DoD and the diverse VA health system data sources; having an overpowered dataset; and using a dataset that was not originally designed to address the study question). Additionally, although private-sector care reimbursed by the VA is included in the analysis, private-sector care paid for by other third-party payers is not included.

Overall, healthcare costs in the TBI group that was identified as CUD only were higher than the dementia-related (Dementia only, Dementia, and CUD) groups. Lower healthcare utilization in the dementia-related groups could be explained by cognitive impairment and behavioral changes, limiting access to or perceived need for care in veterans suffering from dementia. The healthcare cost reduction after 14 years of TBI onset could also be explained by death in the dementia-related subgroups. A better appreciation of the timing and the types of services that are needed and/or accessed by these different subgroups of veterans is vital to optimize the availability and provision of the services. Given the constraints in overall resources across the VA system, it is important to assess the quality of supportive care in outpatient facilities by VA clinicians and administrators and to identify effective approaches to maximize cost-efficient strategies for veterans with TBI and at risk of dementia (11). The impact of the growing number of potential pharmacologic management options for dementia (56) and the extent to which such treatments may delay the need for healthcare services is unknown. Further investigation is needed to examine the impact of the timing of dementia and CUD diagnoses on veterans with TBI, with specific attention to the specific categories of inpatient and outpatient care in VA and community care facilities.

The datasets presented in this article are not readily available due to VA Regulations indicating data behind the firewall. Requests to access the datasets should be directed to: VINCI@VA.GOV.

The studies involving humans were approved by the University of Utah and Stanford University. The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation was not required from the participants or the participants’ legal guardians/next of kin in accordance with the national legislation and institutional requirements.

AE: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Resources, Software, Validation, Visualization, Writing – original draft, Writing – review & editing. TP: Writing – review & editing. MA: Data curation, Software, Formal analysis, Project administration, Writing – review & editing. CG: Project administration, Resources, Software, Writing – review & editing. AN: Writing – review & editing. MM: Project administration, Data curation, Software, Writing – review & editing. MP: Investigation, Supervision, Validation, Writing – review & editing. DC: Supervision, Writing – review & editing. CD-G: Supervision, Writing – review & editing.