ArticleAlzheimer's & dementia (New York, N. Y.)
Evaluation of amyloid change as a surrogate for cognitive decline: demonstration in individual-level data from the A4 study of solanezumab.
Article in Alzheimer's & dementia (New York, N. Y.). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
2 citing papers in PubMed.
- Methodological Considerations for Quantile Aggregation in Alzheimer Disease Trials.JAMA neurology · 2026Article
- Evaluation of amyloid change as a surrogate for cognitive decline: demonstration in individual-level data from the A4 study of solanezumab.Alzheimer's & dementia (New York, N. Y.)Article
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8 authors.
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Abstract
Background: Differential amyloid change has served as a surrogate outcome in Alzheimer's disease trials, allowing accelerated approval of aducanumab and lecanemab. Individual-level data from the A4 study support the demonstration of novel methods to evaluate amyloid's validity as a surrogate for cognitive decline. Methods: In 812 participants, cognitive change was measured using the Clinical Dementia Rating Sum of Boxes (CDR-SB) score. Instrumental-variable analysis estimated the effect of amyloid change; mediation analysis quantified proportion of cognitive effects mediated by amyloid change. Results: Each 10-Centiloid reduction in amyloid due to randomization to treatment was associated with a 0.026 higher CDR-SB score (95% confidence interval [CI]: -0.013, 0.065). Amyloid reduction mediated 14.6% of solanezumab's effect on cognition (95% CI: -122%, 208%). Discussion: Near-zero effect estimates for amyloid change on cognitive decline in the A4 study suggest minimal impact of limited amyloid change reduction in populations with little disease progression. The broader question of validity of amyloid as a surrogate outcome cannot be conclusively answered in data from the A4 study due to study-intrinsic limitations. Replication in anti-amyloid trials with larger treatment effects will evaluate whether amyloid is an appropriate surrogate outcome. Highlights: This study evaluated amyloid change's validity as a surrogate for cognitive and functional decline in AD drug trials.Newly available individual-level trial data from the A4 study enabled the application of epidemiologic and econometric methods to assess amyloid's impact on cognition.IV and causal mediation analyses estimated the effect of amyloid change on cognitive outcomes.Amyloid change mediated 15% of solanezumab's cognitive effect, though estimates were imprecise due to limited disease progression in the sample and solanezumab's minimal amyloid removal.Applying the same methods to data from trials of more effective anti-amyloid drugs could validate amyloid as a surrogate outcome, guide related regulatory decisions, and influence treatment strategy.
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