Do beta-amyloid-targeted interventions improve cognition, physical functioning, and overt behaviour of Alzheimer's Disease (AD) patients: Protocol for meta-analysis of Phase 3 clinical trials both completed and terminated.

Abstract

Accumulation of amyloid-beta (Aβ) in the brain has been explored as a primary cause of Alzheimer's Disease (AD). Better known as the amyloid hypothesis, it has been the main target of researchers vying to bring their therapeutic interventions to market despite several failed attempts by predecessors. In June 2021, Aduhelm (Aducanumab) became the first U.S. Food and Drug Administration (FDA) approved treatment for AD based on the amyloid hypothesis in which sparked controversy. This meta-analysis aims to investigate the efficacy of amyloid-beta targeting interventions at all stages of the disease including the prodromal or mild cognitive impairment (MCI) stage compared to placebo. All completed and terminated Phase III trials are assessed to provide a comprehensive overview of interventions targeting amyloid-beta to inform the legitimacy of the amyloid hypothesis.