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.
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