Abstract
BackgroundA large, prospective, 2-year, randomized study in patients with mild-to-moderate Alzheimer’s disease or mixed dementia demonstrated reductions in mortality and cognitive/functional decline in galantamine-treated patients. A post-hoc analysis was conducted to study the effect of (the presence or absence of) concomitant memantine use on treatment outcome.MethodsRandomized patients (N = 2045) were divided into subgroups based on memantine use. Analyses included demographic and clinical characteristics (age, nursing home placement, Mini-Mental State Examination (MMSE) and Disability Assessment for Dementia (DAD) scores) and mortality endpoints.ResultsOverall, 496 (24.3 %) patients were memantine users and were older (mean (SD), 74.0 (8.76) vs 72.8 (8.76), p = 0.008), with lower MMSE scores (18.2 (4.16) vs 19.2 (4.02), p < 0.0001) and DAD scores (58.0 (23.49) vs 62.5 (20.52), p < 0.0001) than nonusers. Mortality rates (per 100 patient-years) in memantine nonusers (n = 1549) were lower for galantamine (1.39) vs placebo-treated patients (4.15). In memantine users, mortality rates were similar for placebo-treated (4.49) and galantamine-treated patients (5.57). In memantine nonusers at 24 months, the decline in MMSE scores (effect size (95 % CI) 0.25 (0.14; 0.36)) and DAD scores (0.17 (0.06; 0.28)) from baseline was lower in galantamine patients vs placebo patients. The absence of these benefits in memantine users could not be explained by baseline age, MMSE, or DAD scores.ConclusionThis post-hoc analysis shows that the beneficial effects of galantamine at 2 years post treatment were not observed in patients who had been placed on background memantine. The reasons for memantine treatment and the possibility of interaction between memantine and galantamine merit further investigation.Trial registrationClinicalTrials.gov NCT00679627. Registered 15 May 2008.Electronic supplementary materialThe online version of this article (doi:10.1186/s13195-016-0214-x) contains supplementary material, which is available to authorized users.
Highlights
A large, prospective, 2-year, randomized study in patients with mild-to-moderate Alzheimer’s disease or mixed dementia demonstrated reductions in mortality and cognitive/functional decline in galantamine-treated patients
Intention to treat (ITT) with the Last observation carried forward (LOCF) approach was used for Mini-Mental State Examination (MMSE) and Disability Assessment for Dementia (DAD) analysis
Memantine users had slightly lower MMSE and DAD scores compared with the nonusers (MMSE: 18.2 vs 19.2, p < 0.0001; DAD: 58.0 vs 62.5, p < 0.0001)
Summary
A large, prospective, 2-year, randomized study in patients with mild-to-moderate Alzheimer’s disease or mixed dementia demonstrated reductions in mortality and cognitive/functional decline in galantamine-treated patients. Cholinesterase inhibitors have symptomatic benefits across a wide range of dementia severity, as demonstrated in short-term controlled studies ranging from 6 months to 1 year. Galantamine HBr is a reversible, competitive cholinesterase inhibitor and a positive allosteric modulator of nicotinic receptors [2] approved in the USA for the treatment of mild-to-moderately severe dementia of Alzheimer type, and for Alzheimer’s disease (AD) with cerebrovascular disease in certain other countries. A noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist and open-channel blocker of nicotinic receptors, is approved in the USA for the treatment of patients with moderateto-severe dementia of AD [7]. Memantine may be used in combination with a cholinesterase inhibitor because the two have different mechanisms of action and the combination has been thought to further improve cognitive processing [7, 8]
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