TRIAL OF MEMANTINE FOR THE TREATMENT OF PARKINSON'S

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。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。所列机构为中心机构，不一定是研究者机构。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）。PD的早期阶段通常涉及选择性认知障碍，包括记忆、执行、注意力和视觉空间功能的特定缺陷。这些疾病的进展没有得到很好的描述。然而，至少75%的PD患者最终会发展出严重的和全面损害的认知缺陷，与皮质痴呆综合征的特征重叠;痴呆的平均患病率范围为25- 40%。虽然大多数神经退行性疾病缺乏特定的对症治疗，但PD是独特的，因为有效的躯体治疗可用于其主要运动功能以及经常发生的精神障碍。然而，即使PD中的认知缺陷影响日常功能并且是精神障碍的主要风险因素，但对于PD中的认知症状或其进展没有确定的治疗方法。因此，本提案的目标是进行一项小规模的试点研究，以确定美金刚（一种N-甲基-D-天冬氨酸（NMDA）受体拮抗剂）治疗PD患者认知障碍的有效性和耐受性。美金刚（Nemantine）目前已被FDA批准用于治疗阿尔茨海默病。美金刚是一种中等亲和力、非竞争性的N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，可能对PD相关痴呆患者有益。该研究的结果将用于开发一项更大规模的美金刚安慰剂对照试验，并为其他PD认知功能障碍潜在治疗方法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 stages of PD often involve selective cognitive impairments, including specific deficits in memory, executive, attention, and visuospatial functions. The progression of these is not well characterized. However, at least 75% of patients with PD eventually develop severe and globally impairing cognitive deficits that overlap with features of a cortical dementia syndrome; the average prevalence of dementia ranges from 25-40%. Whereas most neurodegenerative disorders lack specific symptomatic treatments, PD is unique in that effective somatic therapies are available for its primary motor features as well as the frequently occurring psychiatric disturbances. Yet, even though cognitive deficits in PD affect everyday functioning and are a major risk factor for psychiatric disturbances, there are no definitive treatments for the cognitive symptoms in PD or their progression. Accordingly, the goal of this proposal is to conduct a small-scale pilot study to determine the effectiveness and tolerability of memantine, a N-methyl-D-aspartate (NMDA)-receptor antagonist for the treatment of cognitive impairment in patients with PD. Memantine (Namenda) is currently approved by the FDA for treatment of Alzheimer's disease. Memantine, a moderate affinity, uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, may be beneficial to patients with dementia in association with PD. Results of the study will be used to develop a larger placebo-controlled trial of memantine, if appropriate, as well as inform the design of other clinical trials on potential treatments for cognitive dysfunction in PD.