EXECUTIVE DYSFUNCTION/PARKINSON' S DISEASE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 帕金森病(PD)的定义是其运动异常和相关的多巴胺能丢失，但它总是伴随着认知障碍[1]。在病程的早期，这些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、定势转移和工作记忆的任务中存在困难，并得到与额叶前区的神经连接的帮助。尽管有致残和痛苦的影响，但几乎没有努力确定这些与帕金森病相关的认知障碍或其进展的治疗方法。因此，这项建议的目标是进行一项小型先导性研究，以确定托莫西汀-一种选择性去甲肾上腺素再摄取抑制剂-治疗帕金森病患者执行功能障碍的有效性和耐受性。 托莫西汀(Strattera)目前被FDA批准用于治疗儿童和成人的注意力缺陷多动障碍(ADHD)。托莫西汀增强了前额叶的多巴胺和去甲肾上腺素能传递，这些区域也与执行功能障碍有关，因此有可能改善帕金森病和其他神经疾病的执行功能障碍(2；3)。如果合适的话，这项研究的结果将被用于开发一项更大规模的托莫西汀安慰剂对照试验，并为其他可能治疗帕金森病认知功能障碍的临床试验的设计提供参考。

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.