Benefits of combined cholinesterase inhibitor and memantine treatment in moderate-severe Alzheimer's disease

Background: Clinical studies and post hoc analyses have investigated the use of combination therapy for the treatment of Alzheimer's disease (AD). We review the evidence for the short- and long-term efficacy of combination therapy in AD. Methods: The review is based on a search of the PubMed database to identify relevant articles concerning combination treatment with memantine and cholinesterase inhibitors (ChEIs). Results: In patients with moderate-to-severe AD, combination treatment with the N-methyl-D-aspartate receptor antagonist memantine and the ChEI donepezil has produced significant benefits in cognition, function, behavior, global outcome, and care dependency, compared with donepezil treatment alone. Data from long-term observational studies support these findings. Compared with ChEI monotherapy, combination treatment slowed cognitive and functional decline (a 4-year sustained effect that appeared to increase over time) and reduced the risk of nursing home admission. Preclinically, the combination of N-methyl-D-aspartate receptor modulation and acetylcholinesterase inhibition has been shown to act synergistically, which may explain the observed clinical effects of combination treatment. Conclusion: Treatment with memantine/ChEI combination therapy in moderate-to-severe AD produces consistent benefits that appear to increase over time, and that are beyond those of ChEI treatment alone. (C) 2013 The Alzheimer's Association. All rights reserved.