AGE, LEAD EXPOSURE, AND NEUROBEHAVIORAL DECLINE

年龄、铅暴露和神经行为衰退

• 批准号: 6202855
• 负责人: WALTER F STEWART
• 金额: $ 84.63万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6202855
• 关键词: aging; apolipoprotein E; blood chemistry; brain disorders; clinical research; cognition disorders; environmental exposure; environmental toxicology; human subject; lead poisoning; longitudinal human study; magnetic resonance imaging; neurotoxins; occupational hazard; tibia

DESCRIPTION (Adapted from applicant's abstract): This is the second resubmission of a competitive renewal application to continue studying the long-term CNS effects of past exposure to organic and inorganic lead. The primary goal of the original study was to determine if past exposure to a putative neurotoxicant was associated with a decline in cognitive function. A unique feature of the cohort we have studied is that none of the participants were occupationally exposed to lead at the time of enrollment. The average time since last exposure was 16 years. We found that past cumulative absorption of lead, measured as tibial lead, was associated with a decline in neurobehavioral test scores, with pronounced declines in tests of verbal and visual memory. Many of the effects were seen in tests that involved declarative new learning, which is known to require the hippocampus and related structures. These progressive changes, comparable to changes in learning and memory associated with aging, long after last occupational exposure to lead are unlikely to be explained by changes in CNS neurochemistry alone. Moreover, our findings are consistent with animal evidence suggesting that organic and inorganic lead can lead to cell death and selectively target areas of the limbic system and epidemiologic evidence that indicates impairment of visual and verbal memory from exposure to inorganic lead. As a logical next step, we propose to determine if there are structural (i.e., MRI based volumetric measures) correlates to the changes in cognitive function we have observed. These data will help determine if there are specific CNS target sites for lead in and will provide the foundation for understanding mechanisms that mediate the effect of adult lead exposure on CNS function, providing an important link between human observational studies and animal experimental studies. To this end we propose: 1. To determine if tibial lead is associated with changes in CNS structures (i.e., smaller brain volumes) suspected as targets of lead. 2. To determine if changes in CNS structures are either in the causal pathway of, or modify the relation between, tibial lead and changes in measures of cognitive function. These aims will be addressed in a three year study of 550 current study participants with past exposure to lead, 100 individuals who participated as controls, and an additional 100 newly recruited subjects with past lead exposure.

描述（改编自申请人摘要）：这是第二个 重新提交竞争性续期申请，以继续学习 过去接触有机和无机铅对中枢神经系统的长期影响。的 最初研究的主要目的是确定过去是否接触过 推定的神经毒物与认知功能下降有关。 我们所研究的队列的一个独特特征是， 在入组时因职业接触铅。的平均时间 因为最后一次接触是16年我们发现过去累积吸收的 以胫骨导联测量的铅与神经行为功能下降相关 在语言和视觉记忆测试中，成绩明显下降。 许多影响都是在涉及陈述性新学习的测试中看到的， 这需要海马体和相关结构。这些 进行性变化，与学习和记忆相关的变化相当 随着年龄的增长，在最后一次职业接触铅之后很长时间， 仅通过中枢神经系统神经化学的变化来解释。此外，我们的发现是， 与动物证据一致，表明有机和无机铅可以 导致细胞死亡并选择性地靶向边缘系统的区域， 流行病学证据表明视觉和语言记忆受损 暴露于无机铅。作为合乎逻辑的下一步，我们建议 确定是否存在结构性（即，基于MRI的体积测量） 与我们观察到的认知功能的变化相关。这些数据 将有助于确定是否有特定的CNS靶点用于导入， 为理解介导以下效应的机制提供基础： 成人铅暴露对中枢神经系统功能的影响，提供了人类之间的重要联系 观察研究和动物实验研究。为此，我们建议： 1.确定胫骨电极导线是否与CNS结构变化相关 (i.e.,脑容量较小）被怀疑是铅的目标。2.以确定是否 中枢神经系统结构的变化要么是在因果关系的途径，或修改 胫骨电极导线与认知功能指标变化之间的关系。 这些目标将在一项为期三年的550项研究中得到解决。 参与者过去接触铅，100人谁参加了作为 对照组和另外100名新招募的既往铅中毒受试者 exposure.