title: Psychometric evaluation of ADAS-Cog and NTB for measuring drug response.
abstract: OBJECTIVE
  To conduct a psychometric analysis to determine the adequacy of instruments that measure cognition in Alzheimer's disease trials.
  
  
  BACKGROUND
  Both the Alzheimer's Disease Assessment Scale - Cognition (ADAS-Cog) and the Neuropsychological Test Battery (NTB) are validated outcome measures for clinical trials in Alzheimer's disease and are approved also for regulatory purposes. However, it is not clear how comparable they are in measuring cognitive function. In fact, many recent trials in Alzheimer's disease patients have failed and it has been questioned if ADAS-Cog still is a sensitive measure.
  
  
  METHODS
  The present paper examines the psychometric properties of ADAS-Cog and NTB, based on a post hoc analysis of data from a clinical trial (NCT01024660), which was conducted by AstraZeneca, in mild-to-moderate Alzheimer's disease (AD) patients, with a Mini Mental State Examination (MMSE) Total score 16-24. Acceptability, reliability, different types of validity and ability to detect change were assessed using relevant statistical methods. Total scores of both tests, as well as separate domains of both tests, including the Wechsler Memory Scale (WMS), Rey Auditory Verbal Learning Test (RAVLT) and Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency Condition, were analyzed.
  
  
  RESULTS
  Overall, NTB performed well, with acceptable reliability and ability to detect change, while ADAS-Cog had insufficient psychometric properties, including ceiling effects in 8 out of a total of 11 ADAS-Cog items in mild AD patients, as well as low test-retest reliability in some of the items.
  
  
  CONCLUSIONS
  Based on a direct comparison on the same patient sample, we see advantages of the NTB compared with the ADAS-Cog for the evaluation of cognitive function in the population of mild-to-moderate AD patients. The results suggest that not all of ADAS-Cog items are relevant for both mild and moderate AD population.
  
  
  CONCLUSIONS
  This validation study demonstrates satisfactory psychometric properties of the NTB, while ADAS-Cog was found to be psychometrically inadequate.
authors.affiliation: AstraZeneca R&D, Södertälje, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Karin
authors.forename: K
authors.initials: K
authors.lastname: Hannesdottir
authors.forename: J
authors.initials: J
authors.lastname: Jaeger
authors.forename: P
authors.initials: P
authors.lastname: Annas
authors.forename: M
authors.initials: M
authors.lastname: Segerdahl
authors.forename: P
authors.initials: P
authors.lastname: Karlsson
authors.forename: N
authors.initials: N
authors.lastname: Sjögren
authors.forename: T
authors.initials: T
authors.lastname: von Rosen
authors.forename: F
authors.initials: F
authors.lastname: Miller
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000188:drug therapy*; D003071:Cognition / Q000187:drug effects*; D000077265:Donepezil; D005260:Female; D006801:Humans; D007189:Indans / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D018697:Nootropic Agents / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use; D011594:Psychometrics; D016032:Randomized Controlled Trials as Topic
chemical_list: D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil
keywords: Alzheimer's Disease Assessment Scale-Cog; Alzheimer's disease; acceptability; ceiling effects; cognitive testing; neuropsychological test battery; psychometric properties; validation