Objective: To investigate the efficacy of donepezil for mild cognitive impairment (MCI) in Parkinson’s disease (PD).

Background: MCI is common in PD. The mechanism of PD-MCI is unclear, but previous studies implicated that cholinergic deficits might be associated with PD-MCI. Donepezil and rivastigmine, acetylcholinesterase inhibitors (AChEIs), increase acetylcholine level and duration of the neurotransmitter action in the synaptic cleft. They are widely used for symptomatic treatment of Alzheimer’s disease. Also, AChEIs had showed moderate improvements of cognition in PD dementia. However, there is no approved treatment in PD-MCI with cholinesterase inhibitor.

Method: This was a prospective, open-label, two-arm study. 80 PD patients with MCI were recruited and assigned to either a treatment or control group. The treatment group received donepezil for 48 weeks. The primary outcome measures were the Korean version of Mini-Mental State Exam (K-MMSE) and Montreal Cognitive Assessment (MoCA) at the baseline, 24-week, and 48-week. Secondary outcome measures were the Clinical Dementia Rating (CDR), Unified Parkinson’s Disease Rating Scale (UPDRS) part III, Clinical Global Impression (CGI) at the baseline, 24-week and 48-week. Comprehensive neuropsychological tests and electroencephalography (EEG) were taken at the baseline and 48-week. Progression of dementia was assessed at 48-week. The spectral power ratio of theta to beta2 band (TB2R) in EEG was analyzed and compared between each group.

Results: Of the 80 patients enrolled, 54 (67.5%) completed the study. Differences in the K-MMSE, MoCA, CDR, UPDRS part III, CGI between both groups at the three assessments and comprehensive neuropsychological test between baseline and 48-week were calculated using a linear mixed model. There were no significant time x group interaction effects. However, the treatment group showed a significant decrease of TB2R at bilateral frontotemporoparietal channels compared to the non-treatment group.

Conclusion: Although we could not demonstrate improvement in the cognitive functions, Donepezil treatment could be beneficial in PD patients with MCI by decreasing the slow-wave relative to the fast wave in EEG, which could reflect the enhancement of brain connectivity.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/donepezil-for-mild-cognitive-impairment-in-parkinsons-disease-a-48-week-follow-up-study/