ImportanceBlast-related mild traumatic brain injuries (TBIs), the “signature injury” of post-9/11 conflicts, are associated with clinically relevant, long-term cognitive, psychological, and behavioral dysfunction and disability; however, the underlying neural mechanisms remain unclear.ObjectiveTo investigate associations between a history of remote blast-related mild TBI and regional brain volume in a sample of US veterans and active duty service members.Design, Setting, and ParticipantsProspective cohort study of US veterans and active duty service members from the Long-Term Impact of Military-Relevant Brain Injury Consortium–Chronic Effects of Neurotrauma Consortium (LIMBIC-CENC), which enrolled more than 1500 participants at 5 sites used in this analysis between 2014 and 2023. Participants were recruited from Veterans Affairs medical centers across the US; 774 veterans and active duty service members of the US military met eligibility criteria for this secondary analysis. Assessment dates were from January 6, 2015, to March 31, 2023; processing and analysis dates were from August 1, 2023, to January 15, 2024.ExposureAll participants had combat exposure, and 82% had 1 or more lifetime mild TBIs with variable injury mechanisms.Main Outcomes and MeasuresRegional brain volume was calculated using tensor-based morphometry on 3-dimensional, T1-weighted magnetic resonance imaging scans; history of TBI, including history of blast-related mild TBI, was assessed by structured clinical interview. Cognitive performance and psychiatric symptoms were assessed with a battery of validated instruments. We hypothesized that regional volume would be smaller in the blast-related mild TBI group and that this would be associated with cognitive performance.ResultsA total of 774 veterans (670 [87%] male; mean [SD] age, 40.1 [9.8] years; 260 [34%] with blast-related TBI) were included in the sample. Individuals with a history of blast-related mild TBI had smaller brain volumes than individuals without a history of blast-related mild TBI (which includes uninjured individuals and those with non–blast-related mild TBI) in several clusters, with the largest centered bilaterally in the superior corona radiata and subcortical gray and white matter (cluster peak Cohen d range, −0.23 to −0.38; mean [SD] Cohen d, 0.28 [0.03]). Additionally, causal mediation analysis revealed that these volume differences significantly mediated the association between blast-related mild TBI and performance on measures of working memory and processing speed.Conclusions and RelevanceIn this cohort study of 774 veterans and active duty service members, robust volume differences associated with blast-related TBI were identified. Furthermore, these volume differences significantly mediated the association between blast-related mild TBI and cognitive function, indicating that this pattern of brain differences may have implications for daily functioning.
