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 and motor function in older adults, with effects more pronounced in women, perhaps due to the loss of neuro-protective estrogen in menopause. On 10 July 1976, a chemical explosion in Seveso, Italy, resulted in one of the highest known residential exposures to TCDD. In 1996, we initiated the Seveso Women's Health Study, a retrospective cohort study of the health of the women who were newborn to 40 years old in 1976. Here, we investigate whether TCDD exposure is associated with physical functioning and working memory more than 20 years later. Individual TCDD concentration (ppt) was measured in archived serum collected soon after the explosion. In 1996 and 2008, we measured physical functioning (n=154) and working memory (n=459), respectively. We examined associations between serum TCDD and motor and cognitive outcomes with multivariate linear regression and semi-parametric estimators. A 10-fold increase in serum TCDD was not associated with walking speed (adjusted β=0.0006 ft/s, 95% Confidence Interval (CI): −0.13, 0.13), upper body mobility (adjusted β=−0.06, 95% CI: −0.36, 0.23), or manual dexterity (adjusted β=0.34, 95% CI: −0.65, 1.33). We observed an inverted U-shaped association in grip strength, with poorer strength in the lowest and highest TCDD exposure levels. There was no association between TCDD and the Wechsler digit and spatial span tests. Neither menopause status at assessment nor developmental timing of exposure modified associations between TCDD and working memory. Our findings, in one of the only studies of TCDD's effects on neuropsychological and physical functioning in women, do not indicate an adverse effect on these domains, with the exception of a U-shaped relationship with grip strength. Given the limited assessment and relative youth of the women at this follow-up, future work examining additional neuropsychological outcomes is warranted.

2,3,7,8-四氯二苯并-对-二恶英 (TCDD) 对动物具有神经毒性，但很少有研究调查其对人脑的影响。相关的二恶英类化合物与老年人认知和运动功能较差有关，对女性的影响更为明显，这可能是由于更年期神经保护雌激素的丧失。 1976 年 7 月 10 日，意大利塞维索发生化学爆炸，导致了已知的 TCDD 暴露最高的住宅之一。 1996 年，我们启动了塞维索​​妇女健康研究，这是一项对 1976 年新生儿至 40 岁妇女健康状况的回顾性队列研究。在此，我们调查了 20 多年来 TCDD 暴露是否与身体机能和工作记忆相关。之后。在爆炸后不久收集的存档血清中测量了个体 TCDD 浓度 (ppt)。 1996 年和 2008 年，我们分别测量了身体机能 (n=154) 和工作记忆 (n=459)。我们使用多元线性回归和半参数估计量检查了血清 TCDD 与运动和认知结果之间的关联。血清 TCDD 增加 10 倍与步行速度（调整后 β=0.0006 ft/s，95% 置信区间 (CI)：-0.13，0.13）、上半身活动能力（调整后 β=-0.06，95% CI）无关：-0.36，0.23），或手动灵巧度（调整后的β=0.34，95％CI：-0.65，1.33）。我们观察到握力呈倒 U 形关联，最低和最高 TCDD 暴露水平的握力较差。 TCDD 与韦氏数字和空间跨度测试之间没有关联。评估时的更年期状态和暴露的发育时间都不会改变 TCDD 和工作记忆之间的关联。 我们的研究结果是唯一一项关于 TCDD 对女性神经心理和身体机能影响的研究，除了与握力的 U 形关系外，并未表明对这些领域有不利影响。鉴于此次随访中女性的评估有限且相对年轻，未来有必要开展检查额外神经心理学结果的工作。