title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: McGill Centre for Studies in Aging, Alzheimer's Disease Research Unit, Montreal, Quebec, Canada. serge.gauthier@mcgill.ca
authors.forename: Serge
authors.initials: S
authors.lastname: Gauthier
authors.forename: José L
authors.initials: JL
authors.lastname: Molinuevo
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D000077265:Donepezil; D015259:Dopamine Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D008559:Memantine / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D002800:Cholinesterase Inhibitors; D015259:Dopamine Agents; D007189:Indans; D010880:Piperidines; D000077265:Donepezil; D008559:Memantine