The report is a product of the VA/HSR Evidence Synthesis Program.

Military Exposure and Risk for Neurological Disease: A Systematic Review

Takeaway: The evidence examining the association between military-related exposures and neurological conditions remains limited, heterogeneous, and in many ways not fully conclusive. The strongest and most consistent associations were found between deployment and incident amyotrophic lateral sclerosis (ALS, a neurodegenerative disease), and between combat and incident headaches. For most other exposure-outcome relationships, studies are too few or show small, inconsistent, or non significant effects. Inconsistent exposure definitions limit comparability across studies. In addition, research examining combined exposures and the influence of exposures on disease severity or progression remains underdeveloped. Still, the results of this review may help inform conversations between clinicians and Veterans by offering clarity as to where evidence does and does not exist. Where evidence is available, it can guide clinicians on how to incorporate exposure history into clinical care in an evidence-informed way. Future studies should include standardized exposure definitions and measures, outcome measures that identify disease trajectory and severity, longitudinal follow-up for late-onset neurological conditions, and sex-specific analyses. VA is well-positioned to support future studies that will help guide clinical care for the growing number of Veterans affected by neurological conditions.

Military-related exposures are diverse, varying in type (e.g., combat, chemical weapons, burn pits), dose, and duration. Although Veterans have higher rates of neurological conditions such as amyotrophic lateral sclerosis (ALS, a neurodegenerative disease) and dementia compared to the general population, links between specific exposures and certain neurological conditions are not completely understood.

In response to a request from the Multiple Sclerosis Center of Excellence, Parkinson’s Disease Research and Educational Clinical Center, Epilepsy Center of Excellence, Headache Center of Excellence, Amyotrophic Lateral Sclerosis System of Care, and the VA Office of Health Outcomes of Military Exposures, HSR’s Evidence Synthesis Program (ESP) Center in Durham, NC, reviewed the evidence on the association between military-related exposures and neurological conditions of priority for VA.

To identify relevant articles, the ESP team searched MEDLINE, Embase, and PsycInfo from inception through November 11, 2025. Additional citations were identified from hand-searching reference lists and consultation with content experts. Exposures were categorized as deployment, combat, blasts, air pollution, chemicals, radiation, heavy metals, and other hazards.

Summary of Findings

• This review included 44 non‑randomized, observational studies that assessed how military-related exposures influence the incidence, severity, or mortality of neurological conditions.
• Deployment, combat, and Agent Orange were the most studied exposures. Exposure definitions and measurement methods varied widely and were often obtained by self-report.
• Most studies focused on disease incidence or mortality using a variety of definitions; very few examined severity or disease progression.
• Many studies, especially those involving recently deployed or exposed populations, had limited follow-up, making it difficult to assess aging-related neurodegenerative or malignant diseases.
• Two meta-analyses by the ESP team found significant associations: deployment with ALS incidence, and combat with headache incidence. A third analysis found a non-significant positive association between blast exposure and epilepsy incidence.
• Four additional meta-analyses found no significant associations between deployment and ALS mortality, brain cancer mortality, multiple sclerosis incidence, or migraine incidence.
• Other exposure-outcome associations were supported by only a small number of studies, and generally showed non‑significant or small effects.
• Key literature gaps include the use of standardized exposure definition and measurement, evaluation of multiple or overlapping exposures, assessment of exposure impact on disease severity or progression, and evaluation of the effect of exposures on functional neurological disorders.

Implications

The evidence linking military-related exposures and neurological conditions remains limited, heterogeneous, and in many ways not fully conclusive. The most consistent positive associations were found between deployment and incident ALS, and between combat and incident headache. The results of this review may help inform conversations between clinicians and Veterans by offering clarity as to where evidence does and does not exist. Where evidence is available, it can guide clinicians on how to incorporate exposure history into clinical care in an evidence-informed way. Continued investment in rigorous research will be essential to help fill the gaps identified by this review and to inform the clinical care of a growing and aging Veteran population.

Limitations

The inclusion criteria used by the ESP team for this review might have excluded relevant evidence. In addition, the review’s findings are constrained by the quality of the available literature. Some studies examined non-U.S. Veterans (which can lead to heterogeneous exposures and preclude generalization to U.S. Veterans), and most of the exposure data were obtained through participants’ self-reporting. Moreover, the analyses in this review were based predominantly on men, which leaves uncertainty about the generalizability of the findings to women Veterans.

Future Research

Future research should include standardized exposure definitions and measurement, outcome measures that identify disease trajectory and severity, longitudinal follow-up for late-onset neurological conditions, and sex-specific analyses. VA is well-positioned to support future studies that explore the association between military-related exposures and neurological conditions.

Citation

Seidenfeld J, Ramos K, Luedke MW, et al. Military Exposure and Risk for Neurological Disease: A Systematic Review. Washington, DC: Evidence Synthesis Program, Health Systems Research, Office of Research and Development, Department of Veterans Affairs. VA ESP Project #09-010; 2026.

To view the full report, go to vaww.hsrd.research.va.gov/publications/esp/military-exposure.cfm (This report is available via intranet only.)

How can VA leadership work with the ESP? Nominations for systematic review topics may be submitted to the program at any time. When you submit a topic nomination form, ESP Coordinating Center staff will work with you to determine the appropriate research approach and ESP product to address your questions of interest. Topics are selected and assigned to an ESP Center based on program capacity and alignment with VA national goals.

This Management Brief is provided to inform you about recent HSR findings that may be of interest. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. If you have any questions or comments about this Brief, please email CIDER. The Center for Information Dissemination and Education Resources (CIDER) is a VA HSR Resource Center charged with disseminating important HSR findings and information to policy makers, managers, clinicians, and researchers working to improve the health and care of Veterans.

This report is a product of VA/HSR's Evidence Synthesis Program (ESP), which was established to provide timely and accurate synthesis of targeted healthcare topics of particular importance to VA managers and policymakers, and to disseminate these reports throughout VA.

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