RWTH Aachen University, Department of Neurology, Pauwelsstraße 30, D-52074 Aachen, Germany.
RWTH Aachen University, Department of Neurology, Pauwelsstraße 30, D-52074 Aachen, Germany.
Neurotoxicology. 2017 Dec;63:106-119. doi: 10.1016/j.neuro.2017.09.011. Epub 2017 Sep 22.
In the context of a health surveillance program for former PCB-exposed workers of a transformer and capacitor recycling company in Germany, their family members, employees of surrounding companies and area residents a broad range of cognitive functions covering attention, executive processing, reasoning, memory and motor performance was examined. The study aimed at identifying potential adverse effects of PCB load on cognitive functions. Detailed analysis of PCB burden of the participants revealed rather high correlations of lower and higher chlorinated as well as dioxin-like PCBs. Nearly one half of the participants exhibited increased burden in all three PCB classes whereas only 33 out of 237 participants did not show any increased PCB burden. Thus, data analysis followed a two-fold strategy: (1) Based on studies providing data on PCB exposure of the German general population the PCB burden of every participant was classified as normal (percentile rank PR <95) or increased (PR ≥95). Increased burden with respect to lower (LPCBs) and higher chlorinated (HPCBs) as well as dioxin-like (dlPCBs) PCBs was assumed if a participant showed at least one congener surpassing the PR95 criterion for the respective congener class and (2) Overall plasma PCB level per congener class was used as measure of PCB load. In a multivariate approach using structural equation modelling and multiple regression analysis we found a significant impact of PCBs on word fluency and sensorimotor processing irrespective of the measure of PCB burden (PR95 criterion or overall plasma level). However, no effect of PCB burden on memory, attention, and cognitive flexibility could be demonstrated. Particularly, an increase of LPCBs was associated with an overall reduction of verbal fluency of letter and semantic word generation as well as word production based on a single or two alternating criteria. In addition, participants with increased burden of LPCBs exhibited a time-on-task effect in terms of a stronger decline of performance with increasing duration of the verbal fluency task. Moreover, we found adverse effects of HPCBs on Aiming and of dlPCBs on Line Tracking. Results are discussed in terms of (1) a decrease of cerebral dopamine (DA) with non-coplanar PCBs resulting in an impact on fronto-striatal cerebral structures subserving verbal fluency and motor processing, (2) a PCB-induced reduction of norepinephrine leading to the time-on-task effect with verbal fluency, and (3) adverse effects of PCBs on dopaminergic receptors in the cerebellum resulting in impaired fine motor function.
在德国一家变压器和电容器回收公司的多氯联苯(PCB)暴露工人及其家属、周边公司员工和当地居民的健康监测项目中,广泛检查了注意力、执行处理、推理、记忆和运动表现等认知功能。该研究旨在确定 PCB 负荷对认知功能的潜在不良影响。对参与者的 PCB 负荷进行的详细分析显示,低氯和高氯以及类二恶英 PCB 的相关性较高。近一半的参与者在所有三个 PCB 类别中都表现出较高的负荷,而在 237 名参与者中只有 33 名没有表现出任何 PCB 负荷增加。因此,数据分析采用了双重策略:(1)基于提供德国普通人群 PCB 暴露数据的研究,将每个参与者的 PCB 负荷分类为正常(百分位 PR<95)或增加(PR≥95)。如果参与者至少有一种同系物超过相应同系物类别的 PR95 标准,则假定其存在低氯(LPCBs)、高氯(HPCBs)和类二恶英(dlPCBs)PCBs 的增加负荷;(2)使用结构方程模型和多元回归分析的多元方法,我们发现 PCB 对单词流畅性和感觉运动处理有显著影响,而与 PCB 负荷的衡量标准(PR95 标准或整体血浆水平)无关。然而,没有发现 PCB 负荷对记忆、注意力和认知灵活性的影响。特别是,LPCBs 的增加与字母和语义单词生成以及基于单个或两个交替标准的单词生成的总体言语流畅性降低有关。此外,LPCBs 负荷增加的参与者在言语流畅性任务中表现出时间任务效应,即随着任务持续时间的增加,表现下降幅度更大。此外,我们发现 HPCBs 对瞄准的影响和 dlPCBs 对线追踪的影响。结果从以下几个方面进行了讨论:(1)非平面 PCB 导致脑内多巴胺(DA)减少,从而影响言语流畅性和运动处理的额纹状体结构;(2)PCB 引起去甲肾上腺素减少,导致言语流畅性的时间任务效应;(3)PCBs 对小脑多巴胺受体的不良影响,导致精细运动功能受损。