title: A meta-analysis of the efficacy of donepezil, rivastigmine, galantamine, and memantine in relation to severity of Alzheimer's disease.
abstract: BACKGROUND
  Randomized clinical trials have evaluated the efficacy of acetylcholinesterase inhibitors (AChE-Is) and memantine across a wide range of Alzheimer's disease (AD) severity. However, these drugs are prescribed and reimbursed according to precise upper and lower cut off scores of cognitive tests.
  
  
  OBJECTIVE
  To verify whether the efficacy of pharmacological treatment had any dependence on the severity of dementia in AD patients.
  
  
  METHODS
  Published English-language randomized, placebo-controlled trials evaluating the efficacy of AChE-Is or memantine at any dose, over any length of time, in patients with any severity of dementia due to AD were included. Cognitive, behavioral, and functional outcomes were extracted from each study and multiple outcomes from the same trial were pooled to obtain a unique indicator of efficacy for cognition, functional impairment, and behavioral and psychological disturbances. The existence of a relationship between size of the treatment effect and severity of dementia, measured with the Mini-Mental State Examination, was determined using parametric and non-parametric correlation analyses.
  
  
  RESULTS
  Both AChE-Is and memantine had significant effects on cognition. Functional and psycho-behavioral outcomes were reported less frequently but also showed significant efficacy of treatment. High heterogeneity among studies was found within and between the different drugs. The efficacy of all drugs except memantine was independent from dementia severity in all domains. Memantine effect on functional impairment was better in more severe patients.
  
  
  CONCLUSIONS
  The modest beneficial effects of anti-dementia drugs on cognition are independent from dementia severity. Memantine is more effective on functional incompetence only in severe patients.
authors: Fondazione IRCCS "Santa Lucia", Roma, Italy. s.disanto@hsantalucia.it
authors: Simona Gabriella
authors: SG
authors: Di Santo
authors: Federica
authors: F
authors: Prinelli
authors: Fulvio
authors: F
authors: Adorni
authors: Carlo
authors: C
authors: Caltagirone
authors: Massimo
authors: M
authors: Musicco
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000523:psychology; D001519:Behavior; D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D003071:Cognition / Q000502:physiology; D003627:Data Interpretation, Statistical; D004185:Disability Evaluation; D018450:Disease Progression; D000077265:Donepezil; D005260:Female; D005702:Galantamine / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007189:Indans / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008559:Memantine / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D009483:Neuropsychological Tests; D048448:Phenylcarbamates / Q000009:adverse effects / Q000627:therapeutic use*; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D000068836:Rivastigmine; D016896:Treatment Outcome
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D018696:Neuroprotective Agents; D048448:Phenylcarbamates; D010880:Piperidines; D005702:Galantamine; D000077265:Donepezil; D000068836:Rivastigmine; D008559:Memantine