A new study of more than 300,000 Vietnam-era U.S. veterans has found that those who were exposed to Agent Orange are nearly twice as likely to develop dementia as those who were not.
The new finding, published Monday in JAMA Neurology, is among the most substantial to date linking cognitive decline with chemicals used for defoliation during the Vietnam War.
For the study, researchers at the San Francisco Veterans Affairs Health Care System examined the medical records of thousands of veterans and found a two-fold risk of dementia for those whose medical records indicated evidence of exposure.
According to Deborah Barnes, a researcher with the University of California San Francisco and the Department of Veterans Affairs, the study authors found that, over the course of time, 5% of veterans with a documented exposure to Agent Orange were diagnosed with dementia compared with 2.5% of vets with no known exposure.
"Even though the absolute rates ... are low, these veterans were still relatively young, so if the risk holds, we would expect that to increase as they age," Barnes said in an interview with JAMA Neurology.
The research also discovered that the exposed vets were diagnosed an average of 15 months earlier than non-exposed veterans -- a finding that can have a huge impact on former personnel, their families and society as a whole, Barnes said.
"Studies have found if we could delay the onset of dementia by a year or 15 months, it would have a huge impact on the population prevalence over time," she explained.
For the study, the researchers reviewed the medical records of Vietnam veterans who received care through the Veterans Health Administration from Oct. 1, 2001, to Sept. 30, 2015. They excluded anyone already diagnosed with dementia and those whose Agent Orange exposure was unclear.
They found that even after adjusting for other factors and conditions that can play a role in the development of dementia -- psychiatric conditions such as post-traumatic stress disorder, medical conditions like diabetes and Parkinson's, or demographic variables -- the two-fold risk remained.
"We did observe that veterans who had a history of Agent Orange exposure were more likely to have PTSD in their medical records or traumatic brain injury, so they did have other conditions that could increase their risk of dementia, so we adjusted statistically and ... yes, there [still] is an association," Barnes said.
Throughout the Vietnam War, U.S. forces sprayed more than 19 million gallons of defoliant, including 11 million of Agent Orange, to clear the jungle and destroy crops. From 1962 to 1971, at least 2.6 million U.S. service members were stationed in Vietnam and other places where the herbicides were sprayed or stored.
Thousands of veterans have been diagnosed with varying types of cancer, heart disease, diabetes, Parkinson's disease and peripheral neuropathy as a result of exposure to the herbicides, according to the VA.
The research didn't explain why exposure may be linked with the development of dementia, but one of the main ingredients of the defoliants -- dioxin -- is known to be stored in fat tissue where it "sticks around for a long time," Barnes said.
"It's possible that Agent Orange stayed in the fat tissue and is slowly being released and causing toxic effects on the brain. But we also know that Agent Orange increases the risk of other disorders that themselves are risk factors for dementia, so it's unclear if it's a direct effect of the dioxin, an indirect effect or possibly a combination," she added.
The researchers said that their study has some limitations, including concerns over the accuracy of Agent Orange exposure documentation in medical records or misclassification of a dementia diagnosis.
Also, the study did not include veterans who receive care outside VA or contain any baseline cognitive scores, which could have revealed whether any of the veterans had undiagnosed dementia at the start.
The researchers suggested that additional studies be conducted to determine the relationship between Agent Orange exposure and dementia and added that they hoped it would encourage physicians to screen their patients for the condition as they age.
Dementia is on the rise in the aging veterans community, with a 20% increase expected among VA patients over the next decade, according to the department.
Barnes said she also would like to see more research on the positive steps patients can take to offset increased risk -- physical activity, healthy lifestyle choices, treating their mental health diagnoses and more.
''We can't change our past. ... What you can control is what you are doing now and what you do in the future. My hope is that, even if these veterans have this risk factor, engaging in a healthier lifestyle may help them offset that risk," she said.