# Computational Drug Repurposing for AD/ADRD with Integrative Analysis of Real World Data and Biomedical Knowledge

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2024 · $766,946

## Abstract

ABSTRACT
Alzheimer’s disease (AD) and AD-related dementia (AD/ADRD) is the 6th leading cause of death in the United
States (US) – is an aging-related neurodegenerative disease with complex pathogenic mechanism affecting an
estimated 6.2 million Americans in 2021. Both the pathogenic mechanism and pathophysiology of AD/ADRD
are complex, creating difficulties in finding effective new treatment or prevention strategies, despite significant
investments in the last decade. On the other hand, the proliferation of large clinical research networks (CRNs)
with real-world data (RWD), such as electronic health records (EHRs), claims, and billing data among others,
offer unique opportunities to generate real-world evidence (RWE) that will have direct translational impacts on
AD/ADRD. In the past, RWD such as EHRs have limited use for AD/ADRD drug repurposing and primarily used
only for validating and evaluating the hypotheses generated by molecular level predictions of AD/ADRD
repurposing agents, partially due to a number of key methodological gaps: (1) the lack of integration with
existing rich biological and pathophysiological knowledge of AD/ADRD for hypothesis generation, (2) the lack of
validated computable phenotyping (CP) and natural language processing (NLP) algorithms and tools that can
accurately define the study populations, extract key relevant patient characteristics and meaningful outcomes
(e.g., MMSE scores to determine severity), (3) the lack of consideration on the heterogeneity of the disease (i.e.,
AD/ADRD subtypes), and (4) the lack of recognition of the inherent biases in RWD and the need of applying
causal inference principles. The goal of this project is to develop a comprehensive machine learning based
causal inference framework for generating high-throughput and high-quality drug repurposing hypotheses for
AD/ADRD by integrating heterogeneous information sources. There are three aims in this project. Aim 1 aims
at developing computable phenotypes to extract key patient characteristics and outcomes relevant to AD/ADRD
drug repurposing studies from RWD. Aim 2 aims at developing a learning-based causal inference framework
for generating drug repurposing hypotheses from RWD, a deep knowledge embedding framework for generating
drug repurposing hypotheses from biomedical knowledge bases (BKB); and a mutual information enhancement
framework that combines the information from both RWD and BKB to further improve the quality of the generated
hypotheses. Aim 3 aims at validating the generated hypotheses with diverse data sources and approaches.
The project will leverage the patient data from two large clinical research networks (CRNs) contributing to the
national Patient-Centered Clinical Research Network (PCORnet) – covering ~15 million Floridians and ~11
million New Yorkers. The developed algorithms and software will be open sourced and widely disseminated
within the CRNs and the AD/ADRD research communities.

## Key facts

- **NIH application ID:** 10814146
- **Project number:** 5R01AG076234-03
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Jiang Bian
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $766,946
- **Award type:** 5
- **Project period:** 2022-03-01 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10814146

## Citation

> US National Institutes of Health, RePORTER application 10814146, Computational Drug Repurposing for AD/ADRD with Integrative Analysis of Real World Data and Biomedical Knowledge (5R01AG076234-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10814146. Licensed CC0.

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