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From Karolinska Institutet (B.W.), Alzheimer’s Disease Research Center, Division of Geriatric Medicine, Stockholm, Sweden; McGill Center for Studies in Aging (S.G.), Quebec, Canada; Harvard Medical School (L.S.), Boston, MA; University of British Columbia (H.F.), Vancouver, Canada; Department of Clinical Geratology (G.K.W.), Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, UK; and Johnson & Johnson Pharmaceutical Research & Development L.L.C. (L.T., A.J.M., D.W., H.R.B., J.S.N.), Titusville, NJ.
Address correspondence and reprint requests to Dr. Jeffrey S. Nye, Johnson and Johnson Pharmaceutical R&D, LLC., P.O. Box 776, Welsh & McKean Roads, Room 31-2002, Spring House, PA 19477-0776 jnye{at}prdus.jnj.com
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 
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 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.
Abbreviations: AD = Alzheimer disease; ADAS-cog/MCI = Alzheimer’s Disease Assessment Scale–cognitive subscale, adapted for use in MCI; ADCS-ADL/MCI = Alzheimer’s Disease Cooperative Study Activities of Daily Living adapted to MCI; AE = adverse event; CDR = Clinical Dementia Rating; CDR-SB = CDR-sum of boxes; DSST = Digit Symbol Substitution Test; ITT = intent-to-treat; MCI = mild cognitive impairment; MMSE = Mini-Mental State Examination; NYU = New York University.
Supplemental data at www.neurology.org
Editorial, page 2020
e-Pub ahead of print on March 5, 2008, at www.neurology.org.
*See the appendix for the list of Group members.
Disclosure: Author disclosures are provided at the end of the article.
Received May 30, 2007. Accepted in final form October 1, 2007.
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