title: A systematic review of assessment and treatment of moderate to severe Alzheimer's disease.
abstract: OBJECTIVE
  The systematic, large-scale study of therapies for moderate to severe Alzheimer's disease (AD) is a relatively recent advancement in the field. This review describes for the general practitioner the characterization of moderate to severe AD, discusses the development of metrics sensitive to the constellation of symptoms in these patients, and critically evaluates the use of those measures in moderate to severe AD clinical trials.
  
  
  METHODS
  Published clinical trials obtained by MEDLINE searches used the following key words: moderate AD, severe AD, donepezil, rivastigmine, galantamine, memantine, and anti-dementia agents. Clinical trials were limited by language (English), study type (clinical trial), and publication dates (1990-2005).
  
  
  METHODS
  Nine clinical trials comprise the studies conducted to date in moderate to severe AD and include 5 prospective randomized clinical trials (3 for memantine, 2 for donepezil) and 4 retrospective subanalyses (2 for galantamine, 2 for rivastigmine) of primary datasets.
  
  
  METHODS
  Clinical trials are summarized and major findings are reviewed.
  
  
  RESULTS
  The data reviewed support the decision to initiate and maintain treatment in moderate to severe AD patients.
  
  
  CONCLUSIONS
  The development and implementation of improved metrics for moderate to severe AD patients has revealed that meaningful benefits are attainable in this patient population by treatment with the N-methyl-D-aspartate receptor antagonist memantine. Evidence also indicates a benefit from cholinesterase inhibitor treatment, although further study of these agents in this patient population is warranted.
authors.affiliation: Departments of Neurology, Psychiatry, Behavioral Sciences, and Psychology, and the Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA. fascom@email.uky.edu
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Schmitt
authors.forename: Christine H
authors.initials: CH
authors.lastname: Wichems