Absent or trivial effects are how a fresh analysis now describes the performance of anti-amyloid drugs for Alzheimer’s disease. The assessment revisits the entire class, from headline-grabbing approvals to abandoned candidates, and questions whether the central amyloid hypothesis is delivering meaningful clinical change.

Anti-amyloid monoclonal antibodies were designed to clear beta-amyloid plaques and modify the pathophysiology of neurodegeneration, and several have secured FDA approval on the back of biomarker shifts and statistically significant but narrow changes in cognitive composite scores. The new review pools data across randomized controlled trials and finds that effect sizes on measures such as the Clinical Dementia Rating and Mini-Mental State Examination often sit close to the threshold of minimal clinically important difference, even as treatment is associated with serious adverse events like amyloid-related imaging abnormalities.

The authors argue that regulatory reliance on surrogate endpoints and marginal p values risks entrenching a high-cost, low-yield therapeutic paradigm while diverting resources from alternative targets, including tau aggregation and neuroinflammation. As payers and health systems confront budget impact models built on these modest hazard ratios for cognitive decline, the gap between statistical significance and lived experience in dementia care is becoming harder to ignore.