Evaluating the clinical relevance of a cognitive composite outcome measure: An analysis of 1414 participants from the 5-year GuidAge Alzheimer's prevention trial.

INTRODUCTION

Composite cognitive scores have been developed as primary outcome measures for preclinical/prevention trials for Alzheimer's disease (AD), mainly using observational data and with little consideration of clinical relevance.

METHODS

Secondary analysis of placebo group data from a 5-year AD prevention trial. The composite score was the average of the following z scores: MMSE orientation items, Free and Cued Selective Reminding Test, Category Fluency, Trail Making Test-part B.

RESULTS

Composite score change from baseline differed significantly by age, APOE genotype, and CDR progression and AD dementia status. A 1 point decrease in baseline score was highly predictive of 5-year AD dementia risk (HR = 3.51, 95% CI, 2.62-4.71, P < .001). The 1 year minimum clinically important difference was estimated at -0.3 points and predicted AD dementia.

DISCUSSION

We explored the clinical relevance of a composite score in a prevention trial setting. This type of analysis facilitates the interpretation of composite scores and informs power calculations.