Memantine for the patients with mild cognitive impairment in Parkinson's disease: a pharmacological fMRI study
Shoji Kawashima1, , Noriyuki Matsukawa2
1Department of Neurology and Neuroscience, Nagoya City University Graduate School of Medical Science, 1 Kawasumi, Mizuho-ku, Nagoya, 467-8601, Japan. shoji@med.nagoya-cu.ac.jp.
Background:
Mild cognitive impairment in Parkinson's disease (PD-MCI) is associated with an increased risk of cognitive decline. PD-MCI is characterized by impairments in executive function and visuospatial recognition. The visuospatial n-back test is useful for assessing both domains. The 0-back test reflects visuospatial recognition, while the 1-back and 2-back tests reflect working memory. Cholinesterase inhibitors are effective in the treatment of PD-MCI and dementia in PD (PDD). Although some studies have reported the efficacy of memantine for PDD, the therapeutic efficacy of memantine in patients with PD-MCI remains uncertain.
Methods:
This study aimed to investigate the effects of memantine on brain function in patients with PD-MCI, using a randomized double-blinded crossover protocol and functional MRI (fMRI). Ten patients who completed 16 weeks of follow-up were included. They were randomly assigned to either the memantine or placebo. Patients in the memantine group received 5 mg/day of memantine in the first week. The memantine dose was increased by 5 mg/day per week, until a final dose of 20 mg/day. Patients in the placebo group received the placebo following the same regimen as memantine. After the intervention, they underwent a 4 weeks washout period. Following the crossover protocol, a second intervention was conducted after the washout period. In each intervention, fMRI and neuropsychological tests were performed at the maximum dose period. Comparing the memantine and placebo groups, we investigated difference in the brain regions using the visuospatial n-back test.
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 during memantine intervention.
Conclusions:
Memantine did not improve visuospatial working memory of the patients with PD-MCI. Treatment for PD should be planned carefully considering the impact on cognitive function. Further study is needed to establish new therapeutic strategy.
Trial Registration:
UMIN000046104. Retrospectively registered. First registration date: 28 Sept 2017.
Insights
Memantine did not improve visuospatial working memory in Parkinson's disease with mild cognitive impairment (PD-MCI). Cognitive function in PD requires careful treatment planning and further research for new strategies.
Area of Science:
- Neuroscience
- Cognitive Science
- Neurology
Background:
- Parkinson's disease with mild cognitive impairment (PD-MCI) presents executive and visuospatial deficits.
- PD-MCI increases the risk of cognitive decline and dementia in Parkinson's disease (PDD).
- The efficacy of memantine for PD-MCI is not well-established, unlike its use in PDD.
Purpose of the Study:
- To investigate the effects of memantine on brain function in PD-MCI patients.
- To assess memantine's impact on visuospatial recognition and working memory using functional MRI (fMRI).
Main Methods:
- Randomized, double-blinded, crossover study with 10 PD-MCI patients.
- 16-week intervention with escalating memantine (up to 20 mg/day) or placebo, followed by a 4-week washout.
- fMRI and neuropsychological tests (visuospatial n-back, Trail Making Test-A) were conducted at maximum dosage.
Main Results:
- Memantine did not enhance brain activation compared to placebo across n-back test loads.
- Significant reductions in activation were observed in the right lingual gyrus and left superior frontal gyrus during the 2-back vs. 0-back comparison.
- Patients performed worse on the 2-back test and Trail Making Test-A during memantine intervention.
Conclusions:
- Memantine failed to improve visuospatial working memory in PD-MCI.
- Cognitive function management in Parkinson's disease necessitates careful consideration of treatment impacts.
- Further research is required to develop effective therapeutic strategies for PD-MCI.
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