Objective: To explore the efficacy of galantamine 24mg/day in patients with very mild AD. Galantamine is a cholinesterase inhibitor that also modulates nicotinic receptors. It has been shown to be effective across all symptomatic domains of Alzheimer’s disease (AD) in several international clinical trials of mild to moderate disease. However, no large trial has studied the effect of galantamine exclusively on patients with very mild AD.
Design: Post-hoc analysis of a sub-set of very mild AD patients pooled from 4 prospective randomized trials (Raskind 2000, Neurology 54:2261; Rockwood 2001, J Neurol Neurosurg Psych 71:589; Tariot 2000, Neurology 54:2269; Wilcock 2000 BMJ 321:1).
Materials and Methods: The very mild subgroup comprised patients with AD diagnosed by NINCDS-ADRA criteria and with baseline Mini Mental State Examination (MMSE) scores >=21. Patients received either galantamine 24mg/day or placebo. The AD Assessment Scale, cognitive subset (ADAS-cog 11) was used to assess cognition, the Clinician’s Interview-Based Impression of Change (CIBIC) was used to record overall change, the Disability Assessment for Dementia (DAD) scale was used to measure functional performance.
Results: This retrospective subgroup comprises 362 patients who received galantamine (GAL) and 332 who received placebo (PLAC). Of these, 65% completed 6 months’ treatment (223 GAL, 229 PLAC). Groups were similar in terms of mean (±SD) MMSE (22.4±1.1) and age (74±7.9 years) at baseline. Mean ADAS-cog scores improved from 19.8 at baseline to 18.4 after 6 months in the galantamine group and remained stable (19.6 to 19.7) in the placebo group. Mean change in ADAS-cog was –1.5 (95% confidence interval –2.2, –0.8, p<0.001) for galantamine and +0.2 (–0.6, 0.9, p=0.72) for placebo. The improvement in GAL patients was observed after 3-4 weeks. More patients receiving galantamine than placebo were classified as ‘improved’ (26.9% GAL vs 14.3% PLAC) using CIBIC (p<0.001). After 3 months, there was no significant change in DAD in the galantamine group (mean change –0.7 (–2.28, 0.88)) compared with a small but significant deterioration in the placebo group (mean change –3.1 (–4.72, –1.57)). There were not enough DAD data at 6 months for a meaningful comparison. Galantamine was generally well tolerated in this subgroup, the most common adverse events were nausea, vomiting and diarrhoea as in the overall population.
Conclusion: Pooled data from 4 randomized trials of patients with very mild AD indicate that patients who received galantamine 24mg/day for 6 months improved cognition and maintained functional abilities significantly more than those who received placebo, and a higher proportion receiving galantamine were classified as globally improved. Therefore patients with very mild AD can obtain significant benefits from galantamine treatment despite the lack of sensitivity of the rating instruments in that severity range. More prolonged trials are needed to determine if this benefit is maintained or increased over time.
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