Objective: This study analyzed the effectiveness of donepezil therapy on neuropsychiatric symptoms in Parkinson’s disease with cognitive impairment (PD-CI), depending on the dose administered.

Background: Although rivastigmine has already been approved for Parkinson’s disease (PD) with dementia (PDD), donepezil has also been often used for the symptomatic treatment of PDD.

Method: Nineteen PD-CI included patients between PD with mild cognitive impairment (PD-MCI) and PDD. Ten patients were taking donepezil 10 mg/day (low-dose), ranging from PD-MCI (Clinical Dementia Rating, CDR 0.5) to mild PDD (CDR 1.0). Nine patients were taking 23 mg/day (high-dose), including those from mild PDD (CDR 1.0) to severe advanced PDD (CDR 2.0 to 3.0). Changes in neuropsychiatric symptoms were observed in each group at baseline and at week 24.

Results: There were significant differences between the two groups in the Korean version of mini-mental status examination and the Montreal Cognitive Assessment, CDR, CDR-sum of boxes (CDR-SB), global deterioration scale (GDS), and neuropsychiatric inventory (NPI). In the high-dose group, the NPI score significantly increased by an average of 10.67 points from baseline at 24 weeks (p = 0.021). However, in the low-dose group, the increase was 1.40 points, which was not statistically significant (p = 0.177).

In the change analysis of NPI subitems, anxiety scores of the low-dose group significantly increased by 0.5 points, indicating worsening symptoms (p = 0.015).

In the high-dose group, anxiety scores decreased by 0.33 points, although this change was not statistically significant (p = 0.74). Hallucination and disinhibition scores decreased (improved) in the high-dose group at 24 weeks, but these changes were not statistically significant (p = 0.907 & p = 0.777). In the low-dose group, scores remained the same or increased. In the apathy, the high-dose group (+2.44, p = 0.809) showed less deterioration than the low-dose group (+3.10, p = 0.188).

Conclusion: The overall NPI score declined more in the high-dose group than in the low-dose group, likely due to higher baseline disease severity in the high-dose group. Although some patients treated with donepezil did not yield statistically significant results, high-dose donepezil may provide better protection against anxiety, disinhibition, hallucinations, and apathy in PDD patients compared to low-dose treatment.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/neuropsychiatric-symptom-changes-in-parkinsons-disease-patients-treated-with-different-doses-of-donepezil-a-24-week-follow-up-study/