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.