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

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.