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

Abstract 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.