Linking the Mini-Mental State Examination, the Alzheimer’s Disease Assessment Scale–Cognitive Subscale and the Severe Impairment Battery: evidence from individual participant data from five randomised clinical trials of donepezil

Abstract

Background The Mini-Mental State Examination (MMSE), the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog) and the Severe Impairment Battery (SIB) are widely used rating scales to assess cognition in Alzheimer’s disease. Objective To understand the correspondence between these rating scales, we aimed to examine the linkage of MMSE with the ADAS-Cog and SIB total and change scores. Methods We used individual-level data on participants with Alzheimer’s disease (n=2925) from five pivotal clinical trials of donepezil. Data were collected at baseline and scheduled visits for up to 6 months. We used equipercentile linking to identify the correspondence between simultaneous measurements of MMSE with ADAS-Cog, and SIB total and change ratings. Findings Spearman’s correlation coefficients were of strong magnitude between the MMSE total score and the ADAS-Cog (rs from −0.82 to −0.87; p<0.05) and SIB total scores (rs from 0.70 to 0.75; p<0.05). Weaker correlations between the change scores were observed between the MMSE change score and the ADAS-Cog (week 1: r=−0.11, p=0.18; rs thereafter: −0.28 to −0.45; p<0.05) and SIB change scores (rs from 0.31 to 0.44; p<0.05). Linking suggested that the MMSE total scores were sensitive to moderate and severe cognitive impairment levels. Despite weak to moderate correlations for the change scores, moderate change levels linked well, indicating ceiling and floor effects. Conclusions The current results can be used in meta-analyses, data harmonisation and may contribute to increasing statistical power when pooling data from multiple sources.