OSCR

Examining the additive risk of TBI and comorbid conditions on dementia in military veterans: a retrospective cohort study.

Overview

Authors: Alexandra L. Clark1,2, Elizabeth Valocchi1, Makenna B. McGill2, Francesca V. Lopez1,3,4, Catherine Chanfreau-Coffinier5, Kelsey R. Thomas1,3,4, Dylan J. Jester6, Mark W. Logue7,8,9,10, Victoria C. Merritt1,3,4
  1. Research Service, VA San Diego Healthcare System,San Diego, CA USA
  2. Department of Psychology, The University of Texas at Austin,Austin, TX USA
  3. Department of Psychiatry, UC San Diego School of Medicine,La Jolla, CA USA
  4. Center of Excellence for Stress and Mental Health (CESAMH), VA San Diego Health Care System,San Diego, CA USA
  5. Center for the Study of Healthcare Innovation, Implementation and Policy (CSHIIP), VA Greater Los Angeles Health Care System,Los Angeles, CA USA
  6. War Related Illness and Injury Study Center (WRIISC), VA Palto Alto Health Care System,Palo Alto, CA USA
  7. National Center for PTSD, Behavioral Sciences Division, VA Boston Healthcare System,Boston, MA USA
  8. Department of Psychiatry, Boston University Chobanian and Avedisian School of Medicine,Boston, MA USA
  9. Biomedical Genetics, Boston University Chobanian and Avedisian School of Medicine,Boston, MA USA
  10. Department of Biostatistics, Boston University School of Public Health,Boston, MA USA
Institutions: VA San Diego Healthcare System (United States); The University of Texas at Austin (United States); University of California San Diego (United States); Center of Excellence for Stress and Mental Health (United States); Center for the Study of Healthcare Provider Behavior (United States); VA Palo Alto Health Care System (United States); VA Boston Healthcare System (United States); Boston University (United States)
Journal: Alzheimer's research & therapy, volume 18, issue 1, article 174
Dates: received 8 December 2025; accepted 12 May 2026; published online 28 May 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1186/s13195-026-02086-5 · PMID 42210358 · PMCID PMC13403857 · OpenAlex W7162645345
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: other (modality), human (organism), Alzheimer's / dementia (population), traumatic brain injury (population), clinical / translational (subfield)
Methods: Statistics
Keywords: Dementia, ADRD, Military Veterans, Traumatic brain injury, Mental health, VA Million Veteran Program
MeSH: Brain Injuries, Traumatic*, Dementia*, Veterans*, Aged, Aged, 80 and over, Cohort Studies, Comorbidity, Female, Humans, Incidence, Male, Retrospective Studies, Risk Factors, United States (* major topic)
Topic: Traumatic Brain Injury Research (Epidemiology, Medicine), according to OpenAlex
Funding: U.S. Department of Veterans Affairs (IK2 CX001952)
Citations: not cited yet (Europe PMC); 45 references in the paper

Abstract

Background: Although 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).

Methods: Participants (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.

Results: Among 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.

Conclusions: Findings 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.

Supplementary Information: The online version contains supplementary material available at 10.1186/s13195-026-02086-5.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

The paper's code and data availability statement is in the Data section.

Tracing map

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Data

Datasets cited

Data availability

The data and code used to generate MVP results are accessible to researchers with MVP data access. Due to VA policy, MVP is currently only accessible to researchers with a funded MVP project (e.g., VA Merit Award, Career Development Award, NIH R01). Thus, the datasets generated and/or analyzed during the current study are not publicly available, but the corresponding author is willing to engage with reasonable requests, share code, and answer questions about the present study. Information about accessing MVP data can be found at:https://www.mvp.va.gov/pwa/joinmvp.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 9 authors, 6 keywords, 14 MeSH terms, 1 funder, 44 references.

Cite

This paper

Clark, A. L., Valocchi, E., McGill, M. B., Lopez, F. V., Chanfreau-Coffinier, C., Thomas, K. R., Jester, D. J., Logue, M. W., & Merritt, V. C. (2026). Examining the additive risk of TBI and comorbid conditions on dementia in military veterans: a retrospective cohort study. Alzheimer's research & therapy, 18(1), 174. https://doi.org/10.1186/s13195-026-02086-5

BibTeX

@article{clark2026examining,
author = {Clark, Alexandra L. and Valocchi, Elizabeth and McGill, Makenna B. and Lopez, Francesca V. and Chanfreau-Coffinier, Catherine and Thomas, Kelsey R. and Jester, Dylan J. and Logue, Mark W. and Merritt, Victoria C.},
title = {{Examining the additive risk of TBI and comorbid conditions on dementia in military veterans: a retrospective cohort study}},
journal = {Alzheimer's research \& therapy},
year = {2026},
month = may,
volume = {18},
number = {1},
pages = {174},
publisher = {BMC},
issn = {1758-9193},
doi = {10.1186/s13195-026-02086-5},
url = {https://doi.org/10.1186/s13195-026-02086-5},
pmid = {42210358},
pmcid = {PMC13403857}
}

RIS

TY - JOUR
AU - Clark, Alexandra L.
AU - Valocchi, Elizabeth
AU - McGill, Makenna B.
AU - Lopez, Francesca V.
AU - Chanfreau-Coffinier, Catherine
AU - Thomas, Kelsey R.
AU - Jester, Dylan J.
AU - Logue, Mark W.
AU - Merritt, Victoria C.
TI - Examining the additive risk of TBI and comorbid conditions on dementia in military veterans: a retrospective cohort study
T2 - Alzheimer's research & therapy
J2 - Alzheimers Res Ther
PY - 2026
DA - 2026/05/28
VL - 18
IS - 1
SP - 174
SN - 1758-9193
PB - BMC
DO - 10.1186/s13195-026-02086-5
UR - https://doi.org/10.1186/s13195-026-02086-5
LA - en
ER -

CSL-JSON

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