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

Eur Neurol. 2012;68(3):137-43. doi: 10.1159/000338774. Epub 2012 Jul 25.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antiparasitic Agents / therapeutic use
  • Brain Mapping
  • Case-Control Studies
  • Cholinergic Agents / metabolism*
  • Cholinesterase Inhibitors / pharmacokinetics
  • Cholinesterase Inhibitors / therapeutic use*
  • Dementia / complications
  • Dementia / diagnostic imaging
  • Dementia / drug therapy*
  • Donepezil
  • Female
  • Humans
  • Indans / pharmacokinetics
  • Indans / therapeutic use*
  • Male
  • Mental Status Schedule
  • Middle Aged
  • Parkinson Disease / complications
  • Parkinson Disease / diagnostic imaging
  • Parkinson Disease / drug therapy*
  • Piperidines / pharmacokinetics
  • Piperidines / therapeutic use*
  • Positron-Emission Tomography


  • (5-methoxy)donepezil
  • Antiparasitic Agents
  • Cholinergic Agents
  • Cholinesterase Inhibitors
  • Indans
  • Piperidines
  • Donepezil