Serum dioxin levels and neuropsychological functioning in the Seveso Women’s Health Study

Abstract

INTRODUCTION: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is neurotoxic in animals but few studies have investigated its effects on the human brain. Related dioxin-like compounds have been linked to poorer cognitive function in adults, with effects more pronounced in women, perhaps due to the loss of neuro-protective estrogen in menopause. METHODS: In 2008, we measured working memory (n=459) via the Wechsler Memory Scale digit span and spatial span tests in the Seveso Women’s Health Study (SWHS), a historical cohort of women residing near Seveso, Italy in 1976, at the time of an industrial explosion which resulted in the highest known population exposure to TCDD. SWHS comprises 981 women who were 0 to 40 years in 1976, resided in the most contaminated areas, and had TCDD concentration measured in archived sera collected soon after the explosion. The associations between 1976 serum TCDD and memory scale scores were modeled with multivariate linear regression and targeted maximum likelihood estimation (tmle). RESULTS: In the 2008 study sample, the geometric mean of 1976 serum TCDD levels was 68.1 (95% confidence interval: 59.8, 77.5) ppt, lipid-adjusted. The average age was 52.3(±11.3) years, with 53% post-menopause in 2008. The proportion of women scoring below the age-scaled median on the digit span (7) and spatial span (8) tests was 44% and 41%, respectively. Adjusting for a priori confounders, a 10-fold increase in TCDD was not associated with performance on the digit span test [β=0.25 (95%CI -0.19, 0.69)], spatial span test (β=0.02 (95%CI -0.44, 0.48), nor their forward and backward components. We did not observe effect modification by menopause status in 2008. DISCUSSION: This is the first study of the exclusive effects of TCDD on cognition in women, particularly surrounding menopause. Our findings do not indicate an adverse effect of dioxin exposure on working memory function in adult women in Italy.