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

Martinez, Steven A.; Yaffe, Kristine; Li, Yixia; Byers, Amy L.; Peltz, Carrie; Barnes, Deborah E.

doi:10.1001/jamaneurol.2020.5011

Cited by 25 publications

(16 citation statements)

References 13 publications

(23 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A recently published brief report by Martinez et al . [ 70 ] shown that deployed U.S. veterans who were exposed to agent orange in the Vietnam era conflict were nearly twice as likely to receive a dementia diagnosis than those not exposed.…”

Section: Military Deployment and Dementiamentioning

confidence: 99%

Dementia in military and veteran populations: a review of risk factors—traumatic brain injury, post-traumatic stress disorder, deployment, and sleep

Raza¹,

Hussain²,

Ftouni³

et al. 2021

Military Med Res

View full text Add to dashboard Cite

The military population face a unique set of risk factors that may increase the risk of being diagnosed with dementia. Traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) have a higher prevalence in this group in comparison to the civilian population. By delving into the individual relationships between TBI and dementia, and PTSD and dementia, we are able to better explore dementia in the military and veteran populations. While there are some inconsistencies in results, the TBI-dementia association has become more widely accepted. Moderate-to-severe TBI has been found to increase the risk of being diagnosed with Alzheimer’s disease. A correlation between PTSD and dementia has been established, however, whether or not it is a causal relationship remains unclear. Factors such as blast, combat and chemical exposure may occur during a deployment, along with TBI and/or PTSD diagnosis, and can impact the risk of dementia. However, there is a lack of literature exploring the direct effects of deployment on dementia risk. Sleep problems have been observed to occur in those following TBI, PTSD and deployment. Poor sleep has been associated with possible dementia risk. Although limited studies have focused on the link between sleep and dementia in military and veteran populations, sleep is a valuable factor to study due to its association and interconnection with other military/veteran factors. This review aims to inform of various risk factors to the cognitive health of military members and veterans: TBI, PTSD, deployment, and sleep.

show abstract

Section: Military Deployment and Dementiamentioning

confidence: 99%

Dementia in military and veteran populations: a review of risk factors—traumatic brain injury, post-traumatic stress disorder, deployment, and sleep

Raza¹,

Hussain²,

Ftouni³

et al. 2021

Military Med Res

View full text Add to dashboard Cite

show abstract

“…The Brief Report titled “Agent Orange Exposure and Dementia Diagnosis in US Veterans of the Vietnam Era,” published online January 25, 2021, had errors in the Figure. The numbers of patients noted in the labels on the 2 lines on the graph should have been reversed, with the upper line labeled “Agent Orange (n = 38 121)” and the lower line labeled “No Agent Orange (n = 278 230).” In addition, on the x-axis, the final value should have been 85, rather than 55, years.…”

mentioning

confidence: 99%

Errors in Figure

2021

JAMA Neurol

View full text Add to dashboard Cite

In Reply We thank Dr Silverman and colleagues for their interest in our study 1 and providing us the opportunity to expand on our results. Among the 1916 patients who visited the emergency department or were hospitalized with coronavirus disease 2019 (COVID-19) in our study, 1 8 patients (0.4% [95% CI, 0.2%-0.8%]) had hemorrhagic stroke, including 7 with intracerebral hemorrhage and 1 with subarachnoid hemorrhage. Among these 8 patients, 4 strokes were attributed to anticoagulant use.Regarding the question about hemorrhagic transformation, 2 of 31 patients with COVID-19 and acute ischemic stroke in our study 1 had symptomatic hemorrhagic transformation. One of these was attributed to intravenous thrombolysis, while the other was attributed to therapeutic-dose anticoagulant use. Overall, 1 of 3 patients (33.3% [95% CI, 8.4%-90.6%]) with COVID-19 who were treated with intravenous thrombolysis for acute ischemic stroke in our cohort developed symptomatic hemorrhagic transformation.We agree that a better understanding of the risks of hemorrhagic stroke in patients with COVID-19 are necessary to inform the risk-benefit assessments of intravenous thrombolysis and anticoagulant therapy for this population. Since the publication of our study, 1 several studies have reported on the risk of hemorrhagic stroke in patients hospitalized with COVID-19. 2,3 We did not collect data on anticoagulant use among patients with COVID-19 who did not have ischemic or hemorrhagic stroke, and therefore we are unable to evaluate the association between anticoagulant use and incident stroke in our cohort. 1 We acknowledge that both prophylactic-dose and therapeutic-dose anticoagulant therapy could affect the incidence of stroke and other thromboembolic events, including by potentially causing net harm through an increase in hemorrhagic stroke. We believe that randomized clinical trials are necessary to determine the safety and efficacy of these treatments. To our knowledge, there are multiple active trials evaluating this question, including the National Institutes of Healthfunded Anti-thrombotics for Adults Hospitalized With COVID-19 (ACTIV-4) trial (NCT04505774). We eagerly await the results of ACTIV-4 and other, similar trials, which hopefully will answer the question of whether anticoagulant use in patients hospitalized with COVID-19 is beneficial.

show abstract

“…To the Editor We were pleased to see the attention of Martinez et al to dementia in veterans of the Vietnam era. However, we are troubled by several important concerns about their study: study population characterization, exposure definition, dementia ascertainment, and a failure to recognize the total environmental exposure milieu of deployment that included Agent Orange.…”

mentioning

confidence: 99%

“…Period of service is a self-reported variable recorded during Veteran Health Administration health care encounters. Department of Defense data on dates and location of deployments would have strengthened population identification …”

mentioning

confidence: 99%

“…Requiring self-reported Agent Orange exposure from at least 1 inpatient and 1 outpatient encounter likely introduced misclassification bias, because this method excludes an unknown proportion of individuals with mild and moderate cases that did not require inpatient care. Furthermore, no specification was provided as to the identification of those who were unexposed …”

mentioning

confidence: 99%

See 1 more Smart Citation

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

2021

View full text Add to dashboard Cite

SIH. MRM and CTM protocols are shown in the eTable in the Supplement.Results were extracted from clinical imaging reports. All discordant studies were reviewed by one neuroradiologist and one neurosurgeon, and in case of disagreement, by a second neuroradiologist to reach consensus.The primary end point was the noninferiority comparison of MRM and CTM. Noninferiority analysis for the proportion (risk) difference was based on the Farrington and Manning likelihood score test. We considered a noninferiority margin of 0.10 to be clinically meaningful. If the lower margin of the 90% confidence interval for difference was more than 0.10, MRM would be considered as noninferior to CTM. We used the 2-sided 95% confidence interval of the difference between the sensitivity of the MRM and sensitivity of the CTM in diagnosing CSF leak. All statistical analyses were performed using SAS, version 9.4 (SAS Institute).Results | Six hundred sixty-seven patients underwent both CTM and MRM (Figure). Five patients had imaging performed more than 6 months apart and 86 patients underwent treatment between imaging modalities. Among the remaining 576 patients, there were 390 women and 186 men (mean age, 48.6 years [range, 13-86 years]). The mean amount of time between CTM and MRM was 6.8 days (range, 0-180 days; <72 hours: 84.1%).Extradural fluid collections 6 were diagnosed in 276 patients (47.9%) by both CTM and MRM (absolute difference, 0.01%; upper limit of 1-sided 95% CI, 3.2%; P < .001 for noninferiority) and 292 patients (50.7%) did not have an extradural CSF collection on both CTM and MRM. Eight patients (1.4%) were a mismatch, with 7 patients (1.2%) being diagnosed by MRM alone and 1 patient (0.2%) by CTM alone. A strong agreement between MRM and CTM with regard to the diagnosis of extradural CSF was found (κ, 97.2%; 95% CI, 95.3-99.1). Positive agreement was 99.6%, negative agreement was 97.7%, and overall agreement was 98.6%.

show abstract

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

Cited by 25 publications

References 13 publications

Dementia in military and veteran populations: a review of risk factors—traumatic brain injury, post-traumatic stress disorder, deployment, and sleep

Dementia in military and veteran populations: a review of risk factors—traumatic brain injury, post-traumatic stress disorder, deployment, and sleep

Errors in Figure

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

Contact Info

Product

Resources

About