Cholinergic deficit and response to donepezil therapy in Parkinson's disease with dementia

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.

To investigate the deficits of the cholinergic system in the brain in PDD and its association with response to donepezil therapy.

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.

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.

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.