Background The ADAS-Cog is a principal outcome measure for clinical trials of Alzheimer's disease (AD). To date decisions on how much change in ADAS-Cog score is clinically relevant has been based on consensus opinion. We aimed to use statistical methodology to establish the minimal clinically relevant change (MCRC) on the ADAS-Cog for patients with mild AD.

Methods We analysed data from the Alzheimer's disease Neuroimaging Initiative. We applied anchor-based MCRC methodology comparing ADAS-cog change against clinicians’ judgement of clinically relevant change 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, we calculated distribution-based measures including half-baseline SD (1/2SD) and SE of measurement (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 change 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 1/2SD for the baseline ADAS-cog score was 3.2, and SEM was 3.7.

Conclusions These data support three point change on the ADAS-Cog as being an appropriate MCRC for clinical trials of patients with early AD.