Related Experiment Video
Updated: Sep 12, 2025
Full- versus Sub-Regional Quantification of Amyloid-Beta Load on Mouse Brain Sections
Published on: May 19, 2022
Evaluation of Amyloid Removal as a Surrogate for Cognitive Decline: Pilot Analysis in Individual-Level Data from the
Sarah F Ackley1, Michael Flanders1, Audrey Murchland2
1Department of Epidemiology, Brown University, 121 S. Main St., Providence, RI 02903.
Background:
Amyloid removal has been used as a surrogate outcome in Alzheimer's disease trials, allowing accelerated approval of aducanumab and lecanemab. The A4 (Alzheimer's Clinical Trial Consortium A4/LEARN) trial's individual-level data supports novel methods to evaluate amyloid's validity as a surrogate for cognitive decline.
Methods:
In 812 participants, cognitive and functional change was measured using the CDR-SB score. Instrumental-variable analysis estimated the effect of amyloid reduction; mediation analysis quantified solanezumab's cognitive effect mediated by amyloid reduction.
Results:
Each 10 centiloid reduction due to randomization to treatment was associated with 0.026 higher CDR-SB (95% CI: -0.013, 0.065). 14.6% of solanezumab's effect on cognition was mediated by amyloid reduction (95% CI: -122%, 208%).
Discussion:
Estimates showing near-zero effects of amyloid reduction on cognitive decline suggest minimal impact of amyloid reduction in populations with little disease progression. Replication in anti-amyloid trials with larger treatment effects could guide treatment and regulatory decisions.
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