title: Cholinergic deficit and response to donepezil therapy in Parkinson's disease with dementia.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Division of Cyclotron Nuclear Medicin, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan. khiraoka@cyric.tohoku.ac.jp
authors: Kotaro
authors: K
authors: Hiraoka
authors: Nobuyuki
authors: N
authors: Okamura
authors: Yoshihito
authors: Y
authors: Funaki
authors: Akiko
authors: A
authors: Hayashi
authors: Manabu
authors: M
authors: Tashiro
authors: Kinya
authors: K
authors: Hisanaga
authors: Toshikatsu
authors: T
authors: Fujii
authors: Atsushi
authors: A
authors: Takeda
authors: Kazuhiko
authors: K
authors: Yanai
authors: Ren
authors: R
authors: Iwata
authors: Etsuro
authors: E
authors: Mori
mesh_terms: D000368:Aged; D000977:Antiparasitic Agents / Q000627:therapeutic use; D001931:Brain Mapping; D016022:Case-Control Studies; D018678:Cholinergic Agents / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003704:Dementia / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*; D000077265:Donepezil; D005260:Female; D006801:Humans; D007189:Indans / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*; D010880:Piperidines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D049268:Positron-Emission Tomography
chemical_list: C473648:(5-methoxy)donepezil; D000977:Antiparasitic Agents; D018678:Cholinergic Agents; D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil