ArticleAlzheimer's research & therapy2026
Examining the additive risk of TBI and comorbid conditions on dementia in military veterans: a retrospective cohort study.
Article in Alzheimer's research & therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundAlthough traumatic brain injury (TBI) has been identified as a risk factor for Alzheimer's disease and related dementias (ADRD), not all studies have shown a clear link between TBI and ADRD, suggesting that the relationship between TBI and ADRD is complex, nuanced, and likely influenced by a multitude of factors. The purpose of this retrospective cohort study was to examine interactions between TBI history and co-occurring health conditions and health behaviors on 10-year incidence of ADRD among Veterans enrolled in the VA Million Veteran Program (MVP).
methodsParticipants (N = 245,949) included Veterans aged ≥ 65 years at study enrollment who completed the MVP Baseline Survey and had VA electronic health record (EHR) data. Participants were followed from the date of MVP enrollment until the earliest ADRD diagnosis, death, or last visit date before the end of the observation period (January 2011 through September 2021). TBI status (TBI + vs. TBI-) and health conditions/health behaviors were characterized using a combination of MVP survey and EHR data. ADRD status (ADRD + vs. ADRD-) was based on a validated algorithm using EHR-extracted ICD codes. Cox proportional hazards regression analyses adjusted for age, sex, and education were used to assess the association between each health condition/health behavior and the hazard of ADRD in the TBI + and TBI- groups. Additive interactions between TBI and health conditions/health behaviors were tested using the relative excess risk due to interaction (RERI) statistic.
resultsAmong Veterans with a TBI history (n = 7,613), 12.16% developed ADRD over 10 years of follow-up; among those without TBI (n = 238,336), 4.32% developed ADRD. RERI analyses showed significant additive TBI by health condition/health behavior interactions for depression (RERI = 1.55, 95% CI = 0.96-2.15), heart attack/coronary artery disease (RERI = 0.76, 95% CI = 0.29-1.24), and physical inactivity (RERI = 0.58; 95% CI = 0.10-1.05), such that ADRD risk in Veterans with TBI was increased for those with these health conditions/health behaviors compared to those without.
conclusionsFindings suggest that ADRD risk following TBI may be heightened in the presence of certain health conditions/health behaviors, highlighting targeted areas of intervention for potentially mitigating adverse late-life outcomes in Veterans with a history of TBI.
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