Safety and efficacy of galantamine in subjects with mild cognitive impairment
Winblad B, Gauthier S, Scinto L, Feldman H, Wilcock GK, Truyen L, et al.;
Commented by , 30 Jun 2008
Aim of the study
To assess the efficacy and safety of galantamine in subjects with mild cognitive impairment (MCI), in regard to cognition, global functioning and progression to dementia.
Method
Two studies totaling 2, 048 subjects age ≥50 with a Clinical Dementia Rating (CDR) of 0.5 at baseline, CDR memory score ≥0.5, Delayed Recall score ≤ 10 on the NYU Paragraph Recall test; randomization was 1:1 to galantamine 16-24mg/day or placebo for 24 months. Primary efficacy endpoint at month 24 was number (%) of subjects who progressed to dementia defined as CDR ≥1.0.
Results
No difference between galantamine and placebo for progression to dementia at 24 months. Mean CDR-sum of boxes declined less with galantamine than placebo at 12 and 24 months in one of the two studies. The most common side-effect was nausea (galantamine 29% vs placebo 10%). Mortality of the cohort after retrospectively determining the status of subjects at 24 months (retrieved drop out study) was 1.4% on galantamine and 0.3% on placebo.
Professor Gauthier's comments
The accompanying editorial by Paul Aisen (ref. 1) puts this study with galantamine in perspective with the other two cholinesterase inhibitors (ChI): no ChI has demonstrated unequivocal benefit in MCI to justify systematic treatment in that population.
He also questions the safety: benefit ratio of such treatment for MCI considering the higher mortality on galantamine relative to placebo in this study, which has not been documented in mild to moderate stages of AD, with or without vascular components.
Much has been learned from these large scales MCI studies: the semi-structured global CDR scale turned out to be sensitive to change over time, and will likely be used in pre-dementia stages of AD.
The sensitivity of the ADAS-cog and other cognitive scales primarily developed for mild to moderate dementia, activities of daily living scales and behavioral scales remains to be established.
Tolerability (more GI side-effects from ChI in MCI than in AD) and safety are critical issues in subjects were many (up to 50%) will not progress to dementia within 5 years.
References
1. Aisen PS. Treatment for MCI: is the evidence sufficient? Neurology 2008; 70 (22); 2020-2021