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Brief Report
January 25, 2021

Agent Orange Exposure and Dementia Diagnosis in US Veterans of the Vietnam Era

Author Affiliations
  • 1San Francisco Veterans Affairs Health Care System, San Francisco, California
  • 2Northern California Institute for Research and Education–The Veterans Health Research Institute, San Francisco
  • 3Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco
  • 4Department of Neurology, University of California, San Francisco, San Francisco
  • 5Department of Epidemiology & Biostatistics, University of California, San Francisco, San Francisco
  • 6Division of Geriatrics, Department of Medicine, University of California, San Francisco, San Francisco
JAMA Neurol. 2021;78(4):473-477. doi:10.1001/jamaneurol.2020.5011
Key Points

Question  Is Agent Orange exposure associated with an increased risk of dementia diagnosis in US veterans of the Vietnam era?

Findings  In this study of more than 300 000 veterans, those with Agent Orange exposure in their medical records were nearly twice as likely as those without exposure to receive a dementia diagnosis, even after adjusting for medical and psychiatric comorbidities and other variables.

Meaning  Per this analysis, Agent Orange exposure may increase risk of dementia.


Importance  Agent Orange is a powerful herbicide that contains dioxin and was used during the Vietnam War. Although prior studies have found that Agent Orange exposure is associated with increased risk of a wide range of conditions, including neurologic disorders (eg, Parkinson disease), metabolic disorders (eg, type 2 diabetes), and systemic amyloidosis, the association between Agent Orange and dementia remains unclear.

Objective  To examine the association between Agent Orange exposure and incident dementia diagnosis in US veterans of the Vietnam era.

Design, Setting, and Participants  This cohort study included Veterans Health Administration data from October 1, 2001, and September 30, 2015, with up to 14 years of follow-up. Analyses were performed from July 2018 to October 2020. A 2% random sample of US veterans of the Vietnam era who received inpatient or outpatient Veterans Health Administration care, excluding those with dementia at baseline, those without follow-up visits, and those with unclear Agent Orange exposure status.

Exposures  Presumed Agent Orange exposure documented in electronic health record.

Main Outcomes and Measures  Fine-Gray competing risk models were used to compare the time to dementia diagnosis (with age as the time scale) for veterans with vs without presumed Agent Orange exposure (as per medical records), adjusting for demographic variables and medical and psychiatric comorbidities.

Results  The total sample was 511 189 individuals; after exclusions, 316 351 were included in analyses. Veterans were mostly male (n = 309 889 [98.0%]) and had a mean (SD) age of 62 (6.6) years; 38 121 (12.1%) had presumed Agent Orange exposure. Prevalence of most conditions, including Parkinson disease, diabetes, and amyloidosis, was similar at baseline among veterans with and without Agent Orange exposure. After adjusting for demographic variables and comorbidities, veterans exposed to Agent Orange were nearly twice as likely as those not exposed to receive a dementia diagnosis over a mean (SD) of 5.5 (3.8) years of follow-up (1918 of 38 121 [5.0%] vs 6886 of 278 230 [2.5%]; adjusted hazard ratio: 1.68 [95% CI, 1.59-1.77]). Veterans with Agent Orange exposure developed dementia at a mean of 1.25 years earlier (at a mean [SD] age of 67.5 [7.0] vs 68.8 [8.0] years).

Conclusions and Relevance  Veterans with Agent Orange exposure were nearly twice as likely to be diagnosed with dementia, even after adjusting for the competing risk of death, demographic variables, and medical and psychiatric comorbidities. Additional studies are needed to examine potential mechanisms underlying the association between Agent Orange exposure and dementia.

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    1 Comment for this article
    Political-Economic-Social Morality of Wars
    Paul Nelson, MS, MD | Family Health Care, P.C.- Retired
    During a 41-year career as a primary physician, it wasn't often that members of our military would reveal to me the inhumanity that our military fostered with the use of Agent Orange. Related to this were the rescue missions that were required to "pickup" beleaguered platoons with aircraft to simultaneously pick up the surrounded troops and shower the surrounding combat zone with literally thousands of bullets unloaded almost simultaneously.
    With just a vague sense of imagination, I could not imagine the severity of imminent catastrophe that the person in front of me must have endured...and endured again by its
    retelling. Fortunately, my nurses always knew to leave his exam-room's door open for me when he came in for a visit.
    The Agent Orange effects were greatly magnified by their emotional disruptive processes.