Longitudinal Cognitive Decline in Alzheimer Disease Prevention Trials: A Test of Time

The landscape of clinical trials for Alzheimer disease (AD) has undergone significant evolution in the past decade, most notably by the inclusion of individuals at progressively earlier stages of the disease. Recent approvals by the Food and Drug Administration have predominantly centered around individuals with prodromal and mild AD,1,2 signaling a shift toward early intervention. Despite the result of some recent trials,3 there is optimism and hope that treating individuals at preclinical stages could have even greater effects. A major challenge for the feasibility and cost-effectiveness of clinical trials on patients with preclinical AD, however, is the fact that cognitive and functional decline over time is mild. Previous studies have already shown the heterogeneity in sensitivity to longitudinal decline across cognitive tests within early disease stages.4,5.