Clinical Progression on CDR-SB : Progression Free Time at Each 0.5-unit Level in Dominantly Inherited and Sporadic Alzheimer's Disease Populations.

Introduction: CDR-SB is a reliable and clinically meaningful composite for assessing treatment effects in Alzheimer's disease (AD) clinical trials. Small CDR-SB differences at the end of a trial often lead to controversy in deriving clinically meaningful interpretations.

Methods: We estimated progression-free time participants remained at each 0.5-unit CDR-SB increment in dominantly inherited AD (DIAD) and sporadic AD populations, evaluating its potential as an alternative measure of treatment effects.

Results: Progression-free time is longer at CDR-SB ≤ 2.0 (1-2 years) and shorter at CDR-SB ≥ 5 (0.33 or less) in the ADNI cohort. The DIAD cohort showed similar but shorter times. Using progression-free time, continuous lecanemab treatment for three years is estimated to delay disease progression by 0.7 years in the sporadic population.

Discussion: Progression-free time provides a benchmark for expressing clinical progression and treatment effects and can be applied particularly during open-label extensions and singlearm trials without placebo comparisons.