title: Donepezil treatment in severe Alzheimer's disease: a pooled analysis of three clinical trials.
abstract: OBJECTIVE
  Individual clinical trials have demonstrated benefits of donepezil in patients with severe Alzheimer's disease (AD). Data were pooled from three randomized, placebo-controlled trials of donepezil for severe AD to further evaluate treatment effects and overall tolerability/safety.
  
  
  METHODS
  Total scores and sub-scores were analyzed for measures of cognition, global function, function, and behavior. Additional analyses were performed to investigate (1) relationships between cognitive, functional, and behavioral changes, and (2) patterns of combined domain response.
  
  
  RESULTS
  Using pooled total scores, significant treatment differences at endpoint in favor of donepezil were observed for cognition, global function (both p < 0.0001), and function (p = 0.03), with an effect size (Cohen's d) of 0.51, 0.26, and 0.17, respectively. There was no significant treatment difference for behavior. However, donepezil-treated patients with stabilized/improved cognition tended to show significant improvements in function and behavior over placebo-treated patients. Patients treated with donepezil were 2-3 times more likely to achieve a combined domain response than placebo-treated patients (p < 0.0001). Adverse events were as expected for cholinergic therapy, and mortality rates were similar between the treatment groups.
  
  
  CONCLUSIONS
  These findings suggest measurable donepezil-mediated symptomatic benefits in cognition, global function, and daily living activities in patients with severe AD. The treatment effects support the importance of cholinesterase inhibition as a clinically relevant therapeutic option across the spectrum of AD.
authors.affiliation: Department of NVS, Karolinska Institutet Alzheimer Disease Research Center, Huddinge, Sweden. bengt.winblad@ki.se
authors.forename: Bengt
authors.initials: B
authors.lastname: Winblad
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Black
authors.forename: Akira
authors.initials: A
authors.lastname: Homma
authors.forename: Elias M
authors.initials: EM
authors.lastname: Schwam
authors.forename: Margaret
authors.initials: M
authors.lastname: Moline
authors.forename: Yikang
authors.initials: Y
authors.lastname: Xu
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Perdomo
authors.forename: Jina
authors.initials: J
authors.lastname: Swartz
authors.forename: Kenneth
authors.initials: K
authors.lastname: Albert
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology; D000077265:Donepezil; D005260:Female; D006801:Humans; D007189:Indans / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D018697:Nootropic Agents / Q000009:adverse effects / Q000627:therapeutic use; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D010919:Placebos; D016032:Randomized Controlled Trials as Topic; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D010919:Placebos; D000077265:Donepezil