Agent Orange Reviewed: Potential Role in Peripheral Neuropathy and Neurodegeneration

Agent Orange, a dioxin-containing toxin, was used as an herbicide during the Vietnam War. Exposures to Agent Orange were initially linked to birth defects among Vietnamese civilians residing near aerially sprayed regions. Years later, returning South Korean and U.S. Veterans exposed to Agent Orange exhibited increased rates of malignancy, cardiovascular disease, diabetes and birth defects in their offspring. Growing evidence that herbicides and pesticides contribute to chronic diseases including neurodegeneration raises concern that Agent Orange exposures may have increased the risk for later development of peripheral or central nervous system (CNS) degeneration. This article reviews published data on the main systemic effects and the prevalence rates, relative risks, characteristics and correlates of Agent Orange-associated peripheral neuropathy and CNS dementia-associated diseases. The critical findings were that relatively high levels of Agent Orange exposure increased risk of developing peripheral neuropathy either alone or as a co-factor complication of diabetes mellitus and likely contributed to the pathogenesis of CNS degenerative diseases, including Alzheimer's, Parkinson's and vascular dementias. Given the protracted intervals between the Agent Orange exposures and disease emergence, additional research is needed to identify mechanistic correlates of the related neurological disorders, including lifestyle co-factors.