EXECUTIVE DYSFUNCTION/PARKINSON' S DISEASE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。帕金森病（PD）的定义是其运动异常和相关的多巴胺能丧失，但它总是伴有认知障碍(1)。在病程早期，缺陷的特征是执行功能障碍，涉及信息处理、注意力、分类、计划、设置转移和工作记忆等任务的困难，并由与前额叶大脑区域的神经连接提供支持。尽管这些pd相关的认知障碍有致残和痛苦的影响，但很少有人努力确定治疗方法。因此，本提案的目标是进行一项小型试点研究，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）。托莫西汀增强多巴胺能和去甲肾上腺素能在前额叶区域的传递，这也与执行功能障碍有关，因此有可能改善PD和其他神经系统疾病的执行功能障碍（2;3）。该研究的结果将用于开发更大的托莫西汀安慰剂对照试验，如果合适的话，并为PD认知功能障碍潜在治疗的其他临床试验的设计提供信息。

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.