Over 6 million patients in the United States are affected by Alzheimer's Disease and Related Dementias (ADRD). Early detection of ADRD can significantly improve patient outcomes through timely treatment.

To develop and validate machine learning (ML) models for early ADRD diagnosis and prediction using de-identified EHR data from the University of Missouri (MU) Healthcare.

Retrospective case-control study.

The study used de-identified EHR data provided by the MU NextGen Biomedical Informatics, modeled with the PCORnet Common Data Model (CDM).

An initial cohort of 380,269 patients aged 40 or older with at least two healthcare encounters was narrowed to a final dataset of 4,012 ADRD cases and 119,723 controls.

Six ML classifier models: Gradient-Boosted Trees (GBT), Light Gradient-Boosting Machine (LightGBM), Random Forest (RF), eXtreme Gradient-Boosting (XGBoost), Logistic Regression (LR), and Adaptive Boosting (AdaBoost) were evaluated using Area Under the Receiver Operating Characteristic Curve (AUC-ROC), accuracy, sensitivity, specificity, and F1 score. SHAP (SHapley Additive exPlanations) analysis was applied to interpret predictions.

The GBT model achieved the best AUC-ROC scores of 0.809–0.833 across 1- to 5-year prediction windows. SHAP analysis identified depressive disorder, age groups 80–90 yrs and 70–80 yrs, heart disease, anxiety, and the novel risk factors of sleep apnea, and headache.

This study underscores the potential of ML models for leveraging EHR data to enable early ADRD prediction, supporting timely interventions, and improving patient outcomes. By identifying both established and novel risk factors, these findings offer new opportunities for personalized screening and management strategies, advancing both clinical and informatics science.