Alzheimers Dement. 2026 Aug;22(8):e71769. doi: 10.1002/alz.71769.
ABSTRACT
The global burden of Alzheimer’s disease (AD) is accelerating, with U.S. prevalence projected to reach nearly 13 million by 2060. Although the “amyloid cascade hypothesis” has long-guided drug development, a 2026 Cochrane review challenged amyloid beta (Aβ) targets for therapy by citing insufficient clinical benefit and safety concerns. We highlight several methodological limitations in this study. The primary concern is a “dilution effect” caused by analyzing monomer-selective antibodies alongside newer treatments that directly target toxic Aβ plaques. This statistical noise, compounded by a decade of failed studies, obscures the significant cognitive preservation achieved by U.S. Food and Drug Administration (FDA)-approved therapies, like lecanemab and donanemab. We contend that these cognitive outcomes are clinically meaningful, as dismissing them ignores the vital impact on preserved independence and reduced caregiver burden. We emphasize current stratified safety frameworks for amyloid-related imaging abnormalities (ARIA) management. The path forward lies in an integrated framework combining Aβ clearance with novel, multi-pathway therapies.
PMID:42625495 | DOI:10.1002/alz.71769
