EXECUTIVE DYSFUNCTION/PARKINSON' S DISEASE

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 帕金森病（PD）的定义是运动异常和相关的多巴胺能损失，但它总是伴随着认知障碍（1）。 在疾病过程的早期，缺陷的特征是执行功能障碍，在涉及信息处理、注意力、分类、计划、设置转换和工作记忆的任务上存在困难，并且通过与前额叶脑区域的神经连接而得以实现。 尽管这些PD相关的认知障碍具有致残和痛苦的影响，但几乎没有努力确定这些PD相关的认知障碍或其进展的治疗方法。 因此，本提案的目的是进行一项小型初探性研究，以确定托莫西汀（一种选择性去甲肾上腺素再摄取抑制剂）治疗PD患者执行功能障碍的有效性和耐受性。 托莫西汀（Strattera）目前已被FDA批准用于治疗儿童和成人的注意力缺陷多动障碍（ADHD）。 托莫西汀可增强前额叶区域的多巴胺能和去甲肾上腺素能传递，这也与执行功能障碍有关，因此有可能改善PD以及其他神经系统疾病中的执行功能障碍（2;3）。 研究结果将用于开发一项更大规模的托莫西汀安慰剂对照试验（如适用），并为其他PD认知功能障碍潜在治疗的临床试验设计提供信息。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Parkinson's disease (PD) is defined by its motor abnormalities and associated dopaminergic loss, but it is invariably accompanied by cognitive impairment (1). Early in the disease course, the deficits are characterized by executive dysfunction with difficulties on tasks that involve information processing, attention, sorting, planning, set-shifting, and working memory and are subserved by neural connections with prefrontal brain regions. There has been little effort to identify treatments for these PD-related cognitive impairments or their progression, despite their disabling and distressing effects. Accordingly, the goal of this proposal is to conduct a small pilot study to determine the effectiveness and tolerability of atomoxetine, a selective norepinephrine reuptake inhibitor, for the treatment of executive dysfunction in patients with PD. Atomoxetine (Strattera) is currently approved by the FDA for treatment of attention deficit hyperactivity disorder (ADHD) in children and adults. Atomoxetine enhances dopaminergic and noradrenergic transmission in prefrontal regions that are also implicated in executive dysfunction and thus has the potential to improve executive dysfunction in PD as well as other neurological conditions (2;3). Results of the study will be used to develop a larger placebo-controlled trial of atomoxetine, if appropriate, as well as inform the design of other clinical trials on potential treatments for cognitive dysfunction in PD.