title: Efficacy of a high dosage of donepezil for Alzheimer's disease as examined by single-photon emission computed tomography imaging.
abstract: BACKGROUND
  The efficacy of donepezil 10 mg/day against Alzheimer's disease (AD) was examined, with a primary focus on changes in cerebral blood flow (CBF) as determined by single-photon emission computed tomography imaging.
  
  
  METHODS
  The subjects were 24 outpatients who had been diagnosed with probable AD, which had progressed to advanced AD. Mini-Mental State Examination and Alzheimer's Disease Assessment Scale (ADAS) scores were determined before and after the donepezil dosage increase. (99m) Tc-ethylcysteinate dimer single-photon emission computed tomography was performed to evaluate changes in CBF. Then, a comparative study evaluated changes after the donepezil dosage increased.
  
  
  RESULTS
  After the donepezil dosage increase, adverse effects associated with gastrointestinal symptoms were observed in one patient, and irritability was observed in three. The average Mini-Mental State Examination score changed from 15.25 ± 6.24 to 14.67 ± 6.07; significant changes were not observed. Seventeen subjects were evaluated with the Alzheimer's Disease Assessment Scale-cognitive subscale. After the dosage increase, the average subscale score decreased from 24.52 ± 13.39 to 21.56 ± 9.14, and significant improvement was observed (P = 0.021). With respect to changes in the CBF, the values of all three indicators decreased after the higher dosage increased CBF. However, no significant differences were observed in CBF. Analysis performed after the donepezil dosage increase revealed significant increases in CBF in the right occipital and temporal lobes, left temporal lobe, right parietal lobe, and both parts of the posterior cerebellum.
  
  
  CONCLUSIONS
  Increasing the donepezil dosage from 5 mg/day to 10 mg/day is effective for the treatment of AD.
authors.affiliation: Department of Geriatric Medicine, Hachioji Medical Center, Tokyo Medical University, Tokyo, Japan. kitikiti@hi-ho.ne.jp
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kanaya
authors.forename: Shine
authors.initials: S
authors.lastname: Abe
authors.forename: Minoru
authors.initials: M
authors.lastname: Sakai
authors.forename: Hiroko
authors.initials: H
authors.lastname: Fujii
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Koizumi
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Iwamoto
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000188:drug therapy*; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage*; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007189:Indans / Q000008:administration & dosage*; D008297:Male; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D010880:Piperidines / Q000008:administration & dosage*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil