PMID- 12442882
OWN - NLM
STAT- MEDLINE
DCOM- 20030320
LR  - 20190910
IS  - 0300-7995 (Print)
IS  - 0300-7995 (Linking)
VI  - 18
IP  - 6
DP  - 2002
TI  - Functional, cognitive and behavioral effects of donepezil in patients with 
      moderate Alzheimer's disease.
PG  - 347-54
AB  - OBJECTIVE: To investigate the efficacy and safety of donepezil in a subgroup of 
      patients with Alzheimer's disease (AD) of moderate severity from a previous 
      trial. METHODS: Two hundred and seven patients with moderate AD (standardized 
      Mini-Mental State Examination [sMMSE] score 10-17) were randomized to treatment 
      in this 24-week, double-blind, placebo-controlled trial. Patents received either 
      donepezil, 5 mg/day for the first 28 days and 10 mg/day thereafter according to 
      the clinician's judgement (n = 102), or placebo (n = 105). The primary outcome 
      measure was the Clinician's Interview-Based Impression of Change with caregiver 
      input (CIBIC-plus) at week 24 using a last observation carried forward (LOCF) 
      analysis. RESULTS: Baseline patient demographics were similar between treatment 
      groups. Mean age was 74.3 years (range 48-92). Least-squares (LS) mean sMMSE 
      scores at baseline were 13.6 +/- 0.3 for the donepezil group and 13.9 +/- 0.3 for 
      the placebo group. LS mean CIBIC-plus scores for donepezil-treated patients were 
      improved from, or close to, baseline severity at all visits, and were 
      significantly different from placebo at weeks 8, 12, 18, and 24 (week 24 LOCF 
      mean difference = 0.53, p = 0.0003). LS mean change from baseline scores on the 
      sMMSE and Severe Impairment Battery (SIB) for the donepezil group improved 
      throughout the study, and were significantly different from placebo at each visit 
      for the sMMSE (week 24 LOCF mean difference = 2.06, p = 0.0002) and from week 8 
      for the SIB (week 24 LOCF mean difference = -4.44, p = 0.0026). LS mean change 
      scores on the Disability Assessment for Dementia remained at or above baseline 
      levels throughout the study for the donepezil group, while the placebo group 
      showed a steady decline; treatment differences were significant at each visit 
      (week 24 LOCF mean difference = -9.25, p < 0.0001). LS mean change scores on the 
      Neuropsychiatric Inventory 12-item total improved throughout the study for the 
      donepezil group and were significantly different from placebo at weeks 4 and 24 
      (week 24 LOCF mean difference = 5.92, p = 0.0022). Eighty-one per cent of 
      donepezil-treated and 89% of placebo-treated patients completed the trial, with 
      9% and 5%, respectively, discontinuing due to adverse events (AEs). Eighty-two 
      per cent of donepezil-treated and 80% of placebo-treated patients experienced 
      AEs, the majority of which were rated mild in severity and, in general, were 
      similar between treatment groups. CONCLUSION: The significant treatment responses 
      observed with donepezil in these patients reinforce the findings from earlier 
      studies that show donepezil to have important benefits, compared wih placebo, 
      across functional, cognitive, and behavioral symptoms, with good tolerability, in 
      patients with AD of moderate severity.
FAU - Gauthier, S
AU  - Gauthier S
AD  - serge.gauthier@mcgill.ca
FAU - Feldman, H
AU  - Feldman H
FAU - Hecker, J
AU  - Hecker J
FAU - Vellas, B
AU  - Vellas B
FAU - Emir, B
AU  - Emir B
FAU - Subbiah, P
AU  - Subbiah P
CN  - Donepezil MSAD Study Investigators' Group
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Curr Med Res Opin
JT  - Current medical research and opinion
JID - 0351014
RN  - 0 (Indans)
RN  - 0 (Nootropic Agents)
RN  - 0 (Piperidines)
RN  - 8SSC91326P (Donepezil)
SB  - IM
MH  - Activities of Daily Living
MH  - Aged
MH  - Aged, 80 and over
MH  - Alzheimer Disease/*drug therapy/physiopathology
MH  - Behavior/*drug effects
MH  - Cognition/*drug effects
MH  - Donepezil
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Indans/adverse effects/*therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Neuropsychological Tests
MH  - Nootropic Agents/*therapeutic use
MH  - Piperidines/adverse effects/*therapeutic use
MH  - Severity of Illness Index
EDAT- 2002/11/22 04:00
MHDA- 2003/03/21 04:00
CRDT- 2002/11/22 04:00
PHST- 2002/11/22 04:00 [pubmed]
PHST- 2003/03/21 04:00 [medline]
PHST- 2002/11/22 04:00 [entrez]
AID - 10.1185/030079902125001029 [doi]
PST - ppublish
SO  - Curr Med Res Opin. 2002;18(6):347-54. doi: 10.1185/030079902125001029.