Development of a straightforward and sensitive scale for MCI and early AD clinical trials

Abstract

Background Although the Clinical Dementia Rating Scale-Sum of Boxes score (CDR-SB) is a widely accepted and commonly used global scale, validated clinical endpoints of cognitive changes are unavailable in the predementia stages of Alzheimer's disease (AD), and a new clinical assessment with reliability and sensitivity is needed in the mild cognitive impairment (MCI) population. Methods Using Alzheimer's Disease Neuroimaging Initiative (ADNI)-1/GO data, signal-to-noise ratios (SNRs) were calculated to quantify the sensitivity of a measure for detecting disease progression and hypothetical treatment effects. All possible combinations of selected sensitive measures were assessed for developing composite scores. The analyses were performed in the MCI population and subpopulations enriched by apolipoprotein E4 (APOE ε4), hippocampal volume, and cerebrospinal fluid β-amyloid. Results The best composite score was "Word Recall + Delayed Word Recall + Orientation + CDR-SB + FAQ", more sensitive than 13-item Alzheimer's Disease Assessment Scale-cognitive subscale or CDR-SB. Conclusion The proposed composite score derived from the existing clinical endpoints demonstrated higher sensitivity in the MCI population and is easy to implement and standardize across studies.