A Pilot Study about the Effectiveness of High-Dose Donepezil in Cognitive Function and Neuropsychiatric Symptoms in Parkinson’s disease with Cognitive Impairment

Background: Donepezil is used for the symptomatic treatment of Alzheimer’s disease (AD), dementia with Lewy bodies (DLB) and Parkinson’s disease (PD) with dementia. Donepezil has been shown to improve behavioral and psychological symptoms of dementia in AD and DLB dose-dependently. We analyzed whether administration of 23 mg/day of donepezil would be more effective than 10 mg/day for both cognitive function and neuropsychiatric symptoms in PD patients with cognitive impairment (CI). Methods: : Ten patients diagnosed with PD by the UK Brain Bank Criteria participated in the study. The cognitive function of patients was adequate according to the criteria for major and minor neurocognitive disorders. Among all patients already taking 10 mg/day donepezil, 3 patients increased the dose to 23 mg/day and then maintained this dose for 24 weeks. Seven of the 10 patients continued the10 mg/day dose for 24 weeks. The Korean version of mini-mental status examination (K-MMSE), Korean version of Montreal Cognitive Assessment (K-MoCA), and caregiver-administered neuropsychiatric inventory (NPI) were examined at baseline and 24 weeks. Results: : Compared to the 23 mg/day group, the 10 mg/day donepezil group showed a younger age at onset and a longer disease duration at baseline. The K-MMSE and K-MoCA scores were higher in the 10 mg/day group than in the 23 mg/day group at baseline. However, the K-MMSE and K-MoCA of the donepezil 23 mg/day group after 24 weeks showed more improvement than those of the donepezil 10 mg/day group. In eight patients who performed the NPI, mood disorders (depression, anxiety, apathy) frequently appeared at both baseline and 24 weeks, in contrast to psychosis (delusion and hallucination). Conclusions: : Compared to 10 mg/day donepezil, 23 mg/day donepezil was more effective in improving cognitive function in PD in a dose-dependent manner. Total scores in NPI showed a worse outcome in the 10 mg/day group after 24 weeks, despite being younger and having less severe parkinsonism compared to the 23 mg/day group. Because psychosis was frequent in PD with dementia, high rates of mood disorders and low rates of psychosis were associated with PD with cognitive impairment in this study.