Cholinergic Deficit and Response to Donepezil Therapy in Parkinson's Disease with Dementia

Background: Although donepezil, an acetylcholinesterase inhibitor, has been proved to be effective in ameliorating cognitive impairment in Parkinson's disease with dementia (PDD), the responsiveness of patients to donepezil therapy varies. [5-(11)C-methoxy]donepezil, the radiolabeled form of donepezil, is a ligand for positron emission tomography (PET), which can be exploited for the quantitative analysis of donepezil binding to acetylcholinesterase and for cholinergic imaging. Objectives: To investigate the deficits of the cholinergic system in the brain in PDD and its association with response to donepezil therapy. Methods: Twelve patients with PDD and 13 normal control subjects underwent [5-(11)C-methoxy]donepezil-PET imaging. For patients with PDD, daily administration of donepezil was started after [5-(11)C-methoxy]donepezil-PET imaging and continued for 3 months. Results: In the PDD group, the mean total distribution volume of the cerebral cortices was 22.7% lower than that of the normal control group. The mean total distribution volume of the patients with PDD was significantly correlated with improvement of visuoperceptual function after 3 months of donepezil therapy. Conclusion: The results suggest that donepezil therapy is more effective in patients with less decrease in acetylcholinesterase, a binding site of donepezil, at least in the specific cognitive domain.