Identifying Alzheimer’s Disease Progression Subphenotypes via a Graph-based Framework using Electronic Health Records

Purpose: Understanding the heterogeneity of neurodegeneration in Alzheimer’s disease (AD) development, as well as identifying AD progression pathways, is vital for enhancing diagnosis, treatment, prognosis, and prevention strategies. To identify disease progression subphenotypes in patients with mild cognitive impairment (MCI) and AD using electronic health records (EHRs). Methods: We identified patients with mild cognitive impairment (MCI) and AD from the electronic health records from the OneFlorida+ Clinical Research Consortium. We proposed an outcome-oriented graph neural network-based model to identify progression pathways from MCI to AD. Results: Of the included 2,525 patients, 61.66% were female, and the mean age was 76. In this cohort, 64.83% were Non-Hispanic White (NHW), 16.48% were Non-Hispanic Black (NHB), and 2.53% were of other races. Additionally, there were 274 Hispanic patients, accounting for 10.85% of the total patient population. The average duration from the first MCI diagnosis to the transition to AD was 891 days. We identified four progression subphenotypes, each with distinct characteristics. The average progression times from MCI to AD varied among these subphenotypes, ranging from 805 to 1,236 days. Conclusion: The findings suggest that AD does not follow uniform transitions of disease states but rather exhibits heterogeneous progression pathways. Our proposed framework holds the potential to identify AD progression subphenotypes, providing valuable and explainable insights for the development of the disease.