What is the clinically relevant change on the ADAS-Cog?

J Neurol Neurosurg Psychiatry. 2012 Feb;83(2):171-3. doi: 10.1136/jnnp-2011-300881. Epub 2011 Oct 21.


Objective: To establish the minimal clinically relevant change (MCRC) on the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) for patients with mild Alzheimer's disease (AD).

Design: Cohort study.

Setting: 59 recruiting sites for the Alzheimer's Disease Neuroimaging Initiative.

Patients: Outpatients with AD in the Alzheimer's Disease Neuroimaging Initiative.

Main outcome measures: The authors applied anchor-based MCRC methodology comparing ADAS-Cog change against clinicians' judgement of clinically relevant worsening between baseline and 6 months in four domains: memory and non-memory cognitive performance; Clinical Dementia Rating Scale; and Functional Assessment Questionnaire. The analysis was repeated for the 6-12-month interval. To support these findings, the authors calculated distribution-based measures including half-baseline SD (1/2 SD) and SEM.

Results: 181 patients (baseline ADAS-Cog score 18.5±6.4) had ADAS-Cog data at 0 and 6 months. Those undergoing clinically significant worsening on any of the four anchor questions (n=41-47) had an average ADAS-Cog change of 3.1-3.8 points. Similar results were found for the 177 patients with 6-12-month data. The average 1/2 SD for the baseline ADAS-Cog score was 3.2, and the SEM was 3.7.

Conclusions: 3 points decline on the ADAS-Cog may be an appropriate MCRC for clinical trials of patients with early AD. However, further studies assessing the MCRC for improvement on the ADAS-Cog, using patient-based judgement as an anchor, and determining the minimal clinically relevant difference between change on two treatments are required.

Clinical trial registration number: http://clinicalTrials.gov Identifier: NCT00106899.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / psychology*
  • Cholinesterase Inhibitors / therapeutic use
  • Cognition / physiology*
  • Cognitive Dysfunction
  • Cohort Studies
  • Educational Status
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Neuropsychological Tests*
  • Nootropic Agents / therapeutic use
  • Surveys and Questionnaires


  • Cholinesterase Inhibitors
  • Nootropic Agents

Associated data

  • ClinicalTrials.gov/NCT00106899