Predicting the potency of anti-alzheimer’s drug combinations using machine learning

Abstract

Clinical trials of single drugs intended to slow the progression of Alzheimer’s Disease (AD) have been notoriously unsuccessful. Combinations of repurposed drugs could provide effective treatments for AD. The challenge is to identify potentially effective combinations. To meet this challenge, machine learning (ML) was used to extract the knowledge from two leading AD data-bases, and then “the machine” predicted which combinations of the drugs in common between the two databases would be the most effective as treatments for AD. Specifically, three-layered artificial neural networks (ANNs) with compound, gated units in their internal layer were trained using ML to predict the cognitive scores of participants, separately in either database, given other data fields including age, demographic variables, comorbidities, and drugs taken. The predictions from the separately trained ANNs were statistically highly significantly correlated. The best drug combina-tions, jointly determined from both sets of predictions, were high in nonsteroidal anti-inflammatory drugs; anticoagulant, lipid-lowering, and antihypertensive drugs; and female hormones. The results suggest that the neurodegenerative processes that underlie AD and other dementias could be effec-tively treated using a combination of repurposed drugs. Predicted drug combinations could be eval-uated in clinical trials.