Bayes analysis supports null hypothesis of anti-amyloid beta therapy in Alzheimer's disease

Alzheimers Dement. 2021 Jun;17(6):1051-1055. doi: 10.1002/alz.12379. Epub 2021 May 31.


Numerous clinical trials of anti-amyloid beta (Aβ) immunotherapy in Alzheimer's disease have been performed. None of these have provided convincing evidence for beneficial effects. Using traditional frequentist meta-analysis, the conclusion is that there is absence of evidence for a therapeutic effect, with a point estimate effect size of 0.05 (95% confidence interval -0.00 to 0.10, P = .055). In addition, this non-significant effect equates to 0.4 points per year on the cognitive subscale of the Alzheimer's Disease Assessment Scale. This is well below the minimally clinically important difference. Bayesian meta-analysis of these trial data provides strong evidence of absence of a therapeutic effect, with a Bayes factor of 11.27 in favor of the null hypothesis, opposed to a Bayes factor of 0.09 in favor of a treatment effect. Bayesian analysis is particularly valuable in this context of repeatedly reported small, non-significant effect sizes in individual trials. Mechanisms other than removal of Aβ from the brain may be probed to slow progression of Alzheimer's disease.

Keywords: Alzheimer's disease; Bayesian analysis; anti-amyloid beta immunotherapy; dementia; evidence of absence; meta-analysis; randomized controlled trial.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Amyloid beta-Peptides / immunology
  • Bayes Theorem*
  • Humans
  • Immunotherapy*
  • Randomized Controlled Trials as Topic*


  • Amyloid beta-Peptides