Randomized Clinical Trial of Donepezil for the Treatment of Mild Cognitive Impairment in Parkinson's Disease

Multicenter, Randomized, Double-blinded, Placebo-controlled Clinical Trial of Donepezil for the Treatment of Mild Cognitive Impairment in Parkinson's Disease

Phase II, multi-centric, randomized, double-blinded, placebo-controlled, parallel design clinical trial to evaluate the safety, tolerability and efficacy of Donepezil in patients with Mild Cognitive Impairment in Parkinson's Disease (PD-MCI). A total of 120 patients with PD-MCI will be randomized to 12 months of oral Donepezil 10mg or matching placebo (1:1).

Primary and co-primary efficacy endpoints are cognitive and functional cognitive scales: PD-CRS and PD-CFRS. Secondary efficacy endpoints include: cognitive tests evaluating attention, executive functions, language, memory and visuospatial domain; mood, anxiety, and apathy scales; questionnaires to evaluate quality of life; and subjective impression scales. Serum Neurofilament light chain, genetic screening of GBA, ApoE and MAPT, and Magnetic Resonance Imaging will be performed in a subset of these patients.

The study will be conducted in 20 different centers around Spain. The Movement Disorders Unit of the Neurology Department at Sant Pau Hospital (Barcelona, Spain) will be the coordinating center.

Inclusion Criteria:

• Age 50-80
• PD diagnosis according to MDS criteria
• Hoehn and Yahr stage I-III
• Persistent subjective cognitive complaints for at least 6 months
• MDS PD-MCI Level I and Level II criteria
• Persistent PD-MCI for at least 3 months
• Stable dopaminergic treatment for at least 1 month

Exclusion Criteria:

• PD dementia criteria
• Severe motor complications
• DBS or any brain condition that may be contributing to cognitive impairment
• Active psychosis, major hallucinations, HADS ≥11, active impulse control disorder, or other active severe behavioral disorders.
• Treatment under anticholinergics, cholinergic enhancers, or neuroleptics.
• History of symptomatic arterial hypotension.
• Hypersensitivity or intolerance to donepezil or any of the excipients
• Pregnancy
• Unstable medical or surgical condition
• Any other significant observation that, in the investigator's opinion, would contraindicate participation in the study.