Background:Mild cognitive impairment of Parkinson's disease (PD-MCI) represents increased risk of future cognitive decline. The characteristics of PD-MCI are impairments in executive function and visuospatial recognition. The visuospatial n-back test has a merit that it can assess both cognitive domains. Concerning the treatment of PD-MCI and dementia in PD (PDD), many studies have reported efficacy of cholinesterase inhibitors. Similarly, some studies reported efficacy of memantine for PDD,

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... wing that it improved clinical status or behavioral symptoms. However, therapeutic evidence of memantine for PD-MCI has not been unestablished. Methods: We aimed to investigate whether memantine can alter brain function of the patients with PD-MCI, using functional MRI. In comparison between memantine and placebo, we explored the difference in regions associated with visuospatial n-back test. The 0-back test reflects visuospatial recognition, and the 1-back and 2-back tests reflect visuospatial working memory. This study followed a randomized double-blind crossover design. Patients in the memantine group were given memantine at 5 mg/day in the first week, and the dose was increased by 5 mg/day per week, with the final dose of 20 mg/day. The patients in the placebo group were given a placebo following the same regimen. The population in this study constitutes 10 patients who completed follow-up. During maximum dose administration, fMRI scanning and neuropsychological tests were performed. Group comparisons between memantine and placebo were performed.Results: There were no significant regions enhanced by memantine comparing with placebo at any load of n-back tests. In contrast, exploring regions reduced by memantine, we found significant reduction of activations within right lingual gyrus and left superior frontal gyrus in comparison between 2-back and 0-back test. A number of correct answers of the 2-back test and time to complete Trail Making Test-A were worse at memantine intervention. Reduced brain activations were associated with worse visuo-spatial working memory caused by memantine.Conclusions:This study reports memantine did not improve visuospatial working memory of the patients with PD-MCI. Treatment of PD should be planned carefully considering the impact for cognitive function. Further study is needed to establish new therapeutic strategy of the patients with PD-MCI.