Exploring the Correlation between the Cognitive Benefits of Drug Combinations in a Clinical Database and the Efficacies of the Same Drug Combinations Predicted from a Computational Model

J Alzheimers Dis. 2019;70(1):287-302. doi: 10.3233/JAD-190144.


Identification of drug combinations that could be effective in Alzheimer's disease treatment is made difficult by the sheer number of possible combinations. This analysis identifies as potentially therapeutic those drug combinations that rank highest when their efficacy is determined jointly from two independent data sources. Estimates of the efficacy of the same drug combinations were derived from a clinical dataset on cognitively impaired elderly participants and from pre-clinical data, in the form of a computational model of neuroinflammation. Linear regression was used to show that the two sets of estimates were correlated, and to rule out confounds. The ten highest ranking, jointly determined drug combinations most frequently consisted of COX2 inhibitors and aspirin, along with various antihypertensive medications. Ten combinations of from five to nine drugs, and the three-drug combination of a COX2 inhibitor, aspirin, and a calcium-channel blocker, are discussed as candidates for consideration in future pre-clinical and clinical studies.

Keywords: Combination therapy; computational modeling; data mining; deep learning; machine learning; microglia; neural network; neuroinflammation; polypharmacy; research database.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Antihypertensive Agents / pharmacology*
  • Antihypertensive Agents / therapeutic use
  • Aspirin / pharmacology*
  • Aspirin / therapeutic use
  • Cognition / drug effects*
  • Computer Simulation
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Cyclooxygenase 2 Inhibitors / therapeutic use
  • Databases, Factual
  • Deep Learning
  • Drug Therapy, Combination
  • Humans
  • Models, Theoretical*
  • Treatment Outcome


  • Antihypertensive Agents
  • Cyclooxygenase 2 Inhibitors
  • Aspirin