TRIAL OF MEMANTINE FOR THE TREATMENT OF PARKINSON'S

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)。PD的早期阶段通常包括选择性认知障碍，包括记忆、执行、注意力和视觉空间功能的特异性缺陷。这些疾病的进展还没有很好地描述。然而，至少75%的PD患者最终发展为与皮质性痴呆综合征特征重叠的严重和全局性认知缺陷；痴呆症的平均患病率在25-40%之间。虽然大多数神经退行性疾病缺乏特异性的对症治疗，但PD的独特之处在于，有效的躯体治疗可用于其主要的运动特征以及经常发生的精神障碍。然而，尽管帕金森病的认知缺陷影响日常功能，并且是精神障碍的主要危险因素，但对于帕金森病的认知症状及其进展尚无明确的治疗方法。因此，本提案的目标是进行一项小规模的试点研究，以确定n -甲基- d -天冬氨酸（NMDA）受体拮抗剂美金刚治疗PD患者认知功能障碍的有效性和耐受性。美金刚（Namenda）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，可能对帕金森病相关痴呆患者有益。这项研究的结果将用于开发一项更大的美金刚安慰剂对照试验，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 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.