Estimated effects of amyloid reduction on cognitive change: A Bayesian update across a range of priors

Authors

Sarah F. Ackley, Department of Epidemiology, Boston University, Boston, Massachusetts, USA.
Jingxuan Wang, Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA.
Ruijia Chen, Department of Epidemiology, Boston University, Boston, Massachusetts, USA.
Melinda C. Power, Department of Epidemiology, George Washington University Milken Institute School of Public Health, Washington, District of Columbia, USA.
Isabel Elaine Allen, Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA.
M Maria Glymour, Department of Epidemiology, Boston University, Boston, Massachusetts, USA.

Document Type

Journal Article

Publication Date

10-30-2023

Journal

Alzheimer's & dementia : the journal of the Alzheimer's Association

DOI

10.1002/alz.13470

Keywords

Alzheimer's disease; amyloid-targeting drugs; amyloid-targeting immunotherapy; dementia; meta-analysis

Abstract

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.

APA Citation

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.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/3536

Department

Epidemiology