PROJECT SUMMARY Most U.S. adults (68%) take dietary supplements and there is increasing evidence of drug-supplement interactions (DSIs); In recent years, there has been increasing evidence supporting the role of DSs in ADRD in preventing cognitive impairment but there is limited evidence and the sample sizes have been small. Real- world data (RWD) especially the EHR contain detailed treatment and response information from patients and could be used to detect the usage and effect of DSs, DSIs, which is more translational to clinical outcomes (e.g., MCI to ADRD conversion). To the best of our knowledge, there is no investigation on DSs usage and safety among patients in MCI and ADRD using EHR data. Our current parent award is focusing on the development of a translational informatics framework to enable the discovery of drug-supplement interactions (DSIs) by linking scientific evidence from the biomedical literature. To response to NOT-AG-20-008, this administrative supplement application will complement our parent award in multiple aspects: (1) developing novel and advanced data analytic methods for mining RWD in EHR, (2) identifying DSs usage information among patients with ADRD, and (3) detecting safety and effect of DS among patients with ADRD from existing EHR data. In our preliminary work, we have investigated the methods to identify DSs terms on EHR and developed natural language processing (NLP) methods to identify use status of DSs. We will further our efforts to collect a EHR dataset with DSs usage and AE-DSs signals from AD patients and develop innovative informatics methods to extract such information. Our specific aims are: (1) identifying DSs usage among patients with MCI and ADRD from existing EHR data; and (2) detecting the DSs safety signals and exploring the effect of DSs use on the conversion from MCI to ADRD from existing EHR data. The successful completion of this project will stimulate our further investigation on the role of DS use in patients with ADRD in a larger scale involving EHR data from other healthcare institutions.