Long-term effects of defoliant exposure on brain atrophy progression in humans

Abstract

As the most toxic dioxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin is classified as a group 1 human carcinogen. We investigated the long-term effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure on the progression of brain atrophy in humans. We retrospectively selected 546 patients exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (exposed group) and 1353 patients not exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (control group). The patients in both groups underwent brain T1-weighted magnetic resonance imaging (MRI) twice. We divided the patients into two propensity score-matched groups, analyzed voxel-wise whole brain atrophy in the MRI images of each patient, and compared the progression of brain atrophy between the two groups. The exposed group showed significant brain atrophy progression in the bilateral frontal and temporal lobes, compared with the control group. The ventrolateral prefrontal area in the frontal lobe and whole temporal lobe were the main atrophic regions in the exposed group, compared with the control group. The neurotoxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin can damage the brain, even in patients exposed to it over 40 years ago. Humans exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin should thus be evaluated for progression of brain atrophy.

Keywords: Agent Orange; Aryl hydrocarbon receptor; Brain; Cerebral atrophy; Dioxin.