title: Greater responsiveness to donepezil in Alzheimer patients with higher levels of acetylcholinesterase based on attention task scores and a donepezil PET study.
abstract: The aim of the study was to predict donepezil responders among patients with Alzheimer disease (AD) based on cognitive tests and positron emission tomography. The Mini-Mental State Examination, Digit Symbol subtest (DigSm) of Wechsler Adult Intelligence Scale Revised, and Trail-Making Test A were administered for 80 patients with AD to assess global function, attention, and executive function, respectively. The same tests and the Clinical Global Impression (CGI) scale were conducted after treatment with oral donepezil (5 mg/d) for 6 months (study 1). [C]-Donepezil positron emission tomography examinations were conducted before and after treatment for 30 randomly selected patients. The distribution volume (DV), which indicates the density of donepezil-binding sites, was calculated using Logan graphical analysis (study 2). In study 1, 35 patients were identified as responders based on the CGI and Mini-Mental State Examination changes. These patients had higher baseline DigSm scores compared with nonresponders. In study 2, 15 patients were responders. DigSm correlated with DV at baseline. DV at baseline and %DV change in responders were higher than in nonresponders, and these variables correlated with ΔDigSm and CGI scores. Higher baseline attention may predict responsiveness to donepezil in patients with AD, and higher acetylcholinesterase levels result in a greater clinical effect.
authors.affiliation: Departments of Geriatric Behavioral Neurology, Tohoku University, Sendai, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Kasuya
authors.forename: Kenichi
authors.initials: K
authors.lastname: Meguro
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Okamura
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Funaki
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Ishikawa
authors.forename: Naofumi
authors.initials: N
authors.lastname: Tanaka
authors.forename: Ren
authors.initials: R
authors.lastname: Iwata
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yanai
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D001288:Attention / Q000502:physiology*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D000077265:Donepezil; D005260:Female; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010880:Piperidines / Q000627:therapeutic use*; D049268:Positron-Emission Tomography
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil; D000110:Acetylcholinesterase