Alzheimer’s & Dementia: Translational Research & Clinical Interventions (Apr 2025)
Measuring time saved in Alzheimer's disease: What is a meaningful slowing of progression?
Abstract
Abstract INTRODUCTION Minimal clinically important differences (MCIDs) for Alzheimer's disease (AD) have previously been estimated using clinician‐based anchors. However, MCIDs have been criticized for not reflecting the preferences of people living with AD (PLWAD). Furthermore, interpretations of clinical trial results have been criticized for conflating within‐person meaningfulness thresholds and between‐group differences. Here, we simulate scenarios of disease slowing and compare those to published MCIDs. METHODS Scenarios of 5%–95% disease slowing were simulated using Alzheimer's Disease Neuroimaging Initiative (ADNI) data. Time saved and point differences on the Clinical Dementia Rating scale—Sum of Boxes (CDR‐SB) were estimated for these scenarios and compared to published MCIDs. RESULTS Scenario analyses resulted in estimates of time saved at ∼3 weeks–17 months and mean changes at 0.08–1.5 CDR‐SB points over 18 months. The often referenced MCID for mild cognitive impairment (0.98) thereby corresponded to 11 months slowing, whereas the MCID for mild dementia (1.63) corresponded to >17 months slowing. DISCUSSION Translating trial endpoints to estimates of time saved supports that often‐referenced MCIDs may not be aligned with realistic and meaningful slowing of clinical progression. Highlights AD slowing of clinical progression by 5%–95% resulted in 0.74–17 months saved and 0.08–1.5 CDR‐SB points change at 18 months. Slowing of at least 60% or 11 months of time saved over 18 months met an often‐cited MCID threshold of 0.98 points for mild cognitive impairment. For mild AD dementia, an MCID of 1.63 meant that even an 18‐month delay over 18 months would be considered only borderline meaningful—a face invalid and unrealistic proposition.
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