Exploring Potential Medications for Alzheimer’s Disease with Psychosis by Integrating Drug Target Information into Deep Learning Models: A Data-Driven Approach

Abstract

Approximately 50% of Alzheimer’s disease (AD) patients develop psychotic symptoms, leading to a subtype known as psychosis in AD (AD + P), which is associated with accelerated cognitive decline compared to AD without psychosis. Currently, no FDA-approved medication specifically addresses AD + P. This study aims to improve psychosis predictions and identify potential therapeutic agents using the DeepBiomarker deep learning model by incorporating drug–target interactions. Electronic health records from the University of Pittsburgh Medical Center were analyzed to predict psychosis within three months of AD diagnosis. AD + P patients were classified as those with either a formal psychosis diagnosis or antipsychotic prescriptions post-AD diagnosis. Two approaches were employed as follows: (1) a drug-focused method using individual medications and (2) a target-focused method pooling medications by shared targets. The updated DeepBiomarker model achieved an area under the receiver operating curve (AUROC) above 0.90 for psychosis prediction. A drug-focused analysis identified gabapentin, amlodipine, levothyroxine, and others as potentially beneficial. A target-focused analysis highlighted significant proteins, including integrins, calcium channels, and tyrosine hydroxylase, confirming several medications linked to these targets. Integrating drug–target information into predictive models improves the identification of medications for AD + P risk reduction, offering a promising strategy for therapeutic development.