title: Safety and efficacy of galantamine in subjects with mild cognitive impairment.
abstract: OBJECTIVE
  To assess the safety of galantamine in subjects with mild cognitive impairment (MCI), the ability of galantamine to benefit cognition and global functioning in subjects with MCI, and the ability of galantamine to delay conversion to dementia.
  
  
  METHODS
  In two studies, 2,048 subjects, 990 in Study 1 and 1,058 in Study 2, with a Clinical Dementia Rating (CDR) = 0.5, CDR memory score > or =0.5, without dementia were randomized to double-blind galantamine (16-24 mg/day) or placebo for 24 months. Primary efficacy endpoint at month 24 was number (%) of subjects who converted from MCI to dementia (CDR > or = 1.0).
  
  
  RESULTS
  There were no differences between galantamine and placebo in 24-month conversion rates (Study 1: 22.9% [galantamine] vs 22.6% [placebo], p = 0.146; Study 2: 25.4% [galantamine] vs 31.2% [placebo], p = 0.619). Mean CDR-sum of boxes declined less with galantamine than placebo at 12 and 24 months in Study 1 (p = 0.024 [12 months] and p = 0.028 [24 months]), but not in Study 2 (p = 0.662 [12 months] and p = 0.056 [24 months]). Digit Symbol Substitution Test scores improved with galantamine in Study 1 at 12 months and in Study 2 at 24 months (Study 1: p = 0.009 [month 12] and p = 0.079 [Month 24]; Study 2: p = 0.154 [month 12] and p = 0.020 [month 24]). The most frequently reported adverse event was nausea (galantamine, 29%; placebo, 10%). Serious AEs occurred in 19% of each group. Mortality of the cohort after retrospectively determining the status of subjects (98.3%) at 24 months was 1.4% (galantamine) and 0.3% (placebo); RR (95% CI), 1.70 (1.00, 2.90).
  
  
  CONCLUSIONS
  Galantamine failed to significantly influence conversion to dementia. Galantamine was generally well tolerated. Whereas recorded mortality was greater in the galantamine group than in the placebo group in the original per-protocol assessment, a post hoc analysis of the cohort was consistent with no increased risk.
authors.affiliation: Karolinska Institutet, Alzheimer's Disease Research Center, Division of Geriatric Medicine, Stockholm, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Winblad
authors.forename: S
authors.initials: S
authors.lastname: Gauthier
authors.forename: L
authors.initials: L
authors.lastname: Scinto
authors.forename: H
authors.initials: H
authors.lastname: Feldman
authors.forename: G K
authors.initials: GK
authors.lastname: Wilcock
authors.forename: L
authors.initials: L
authors.lastname: Truyen
authors.forename: A J
authors.initials: AJ
authors.lastname: Mayorga
authors.forename: D
authors.initials: D
authors.lastname: Wang
authors.forename: H R
authors.initials: HR
authors.lastname: Brashear
authors.forename: J S
authors.initials: JS
authors.lastname: Nye
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000401:mortality / Q000517:prevention & control; D003072:Cognition Disorders / Q000188:drug therapy* / Q000401:mortality / Q000523:psychology*; D015331:Cohort Studies; D004311:Double-Blind Method; D005260:Female; D005702:Galantamine / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D005702:Galantamine