title: Measuring therapeutic efficacy in patients with Alzheimer's disease: role of instruments.
abstract: OBJECTIVE
  Global cognitive scales and meta-analyses thereof are used to appraise therapeutic efficacy over a broad range of disease severity. Clinically, however, different aspects of cognition change in different stages of disease.
  
  
  METHODS
  Calculation of effect sizes for single cognitive functions on treatment as assessed by the Alzheimer's Disease Assessment Scale (ADAS-cog), the Mini-Mental-Status Examination (MMSE), and the Severe Impairment Battery (SIB). In these scales, subdomains of 'cognition', e.g. memory and language, are represented in different proportions. To exemplify the analysis of 'cognition', we used original data of previously published clinical studies with memantine.
  
  
  RESULTS
  Depending on dementia severity and on the scale used, the effect size for memory varies between -0.44 and +0.34 and for language between -0.40 and +0.26.
  
  
  CONCLUSIONS
  Beyond interstudy variance, effect sizes for treatment with antidementia drugs are subject to disease stage, instruments used, and interaction thereof. Therefore, clinical interpretation is necessary to appraise therapeutic efficacy in clinical studies and meta-analyses thereof when patients with different severity are included or different instruments are used. Alternatively, severity-adapted endpoints should be used for appraisal and meta-analysis of therapeutic efficacy.
authors.affiliation: Department of Psychiatry and Psychotherapy II, Mental Health and Old Age Psychiatry, Ulm University, Ludwig-Heilmeyer-Strasse 2, Günzburg, Germany. matthias.riepe@uni-ulm.de
authors.forename: Matthias W
authors.initials: MW
authors.lastname: Riepe
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Janetzky
authors.forename: Ole M
authors.initials: OM
authors.lastname: Lemming
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D018450:Disease Progression; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D006801:Humans; D008559:Memantine / Q000627:therapeutic use*; D015201:Meta-Analysis as Topic; D017063:Outcome Assessment, Health Care / Q000379:methods*; D011569:Psychiatric Status Rating Scales; D012107:Research Design; D018401:Sample Size; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D018691:Excitatory Amino Acid Antagonists; D008559:Memantine