Estimated effects of amyloid reduction on cognitive change: A Bayesian update across a range of priors
Alzheimer's & dementia : the journal of the Alzheimer's Association
Alzheimer's disease; amyloid-targeting drugs; amyloid-targeting immunotherapy; dementia; meta-analysis
INTRODUCTION: The results of the CLARITY-AD, GRADUATE I and II, and TRAILBLAZER-ALZ 2 trials have rekindled discussion on the impact of amyloid-targeting drugs. We use a Bayesian approach to quantify how rational observers would have updated their prior beliefs based on new trial results. METHODS: We used publicly available data from the CLARITY-AD, GRADUATE I and II, and TRAILBLAZER-ALZ 2 trials to estimate the effect of reducing amyloid on the clinical dementia rating scale, sum of boxes (CDR-SB) score. A range of prior positions were then updated according to Bayes' theorem using these estimates. RESULTS: After updating with new trial data, a wide range of starting positions resulted in credible intervals that did not include no effect of amyloid reduction on CDR-SB score. DISCUSSION: For a range of starting beliefs and assuming the veracity of the underlying data, rational observers would conclude there is a small benefit of amyloid reductions on cognition. This benefit must be weighed against opportunity cost and side-effect risk. HIGHLIGHTS: The results of recent trials of amyloid-targeting drugs have rekindled discussion on the impact of amyloid reductions achieved with amyloid-targeting drugs on cognition. Prior to the announcement of trial results, beliefs about the effects of altering amyloid levels varied. For a range of starting beliefs, one would conclude there is a small benefit of amyloid reductions due to amyloid-targeting drugs on cognition. The perceived value of individual drugs must balance the magnitude of this benefit against opportunity cost and risk of side effects.
Ackley, Sarah F.; Wang, Jingxuan; Chen, Ruijia; Power, Melinda C.; Allen, Isabel Elaine; and Glymour, M Maria, "Estimated effects of amyloid reduction on cognitive change: A Bayesian update across a range of priors" (2023). GW Authored Works. Paper 3536.