Explainable Machine Learning with Pairwise Interactions for Predicting Conversion from Mild Cognitive Impairment to Alzheimer’s Disease Utilizing Multi-Modalities Data

Background: Predicting cognition decline in patients with mild cognitive impairment (MCI) is crucial for identifying high-risk individuals and implementing effective management. To improve predicting MCI-to-AD conversion, it is necessary to consider various factors using explainable machine learning (XAI) models which provide interpretability while maintaining predictive accuracy. This study used the Explainable Boosting Machine (EBM) model with multimodal features to predict the conversion of MCI to AD during different follow-up periods while providing interpretability. Methods: This retrospective case-control study is conducted with data obtained from the ADNI database, with records of 1042 MCI patients from 2006 to 2022 included. The exposures included in this study were MRI biomarkers, cognitive scores, demographics, and clinical features. The main outcome was AD conversion from aMCI during follow-up. The EBM model was utilized to predict aMCI converting to AD based on three feature combinations, obtaining interpretability while ensuring accuracy. Meanwhile, the interaction effect was considered in the model. The three feature combinations were compared in different follow-up periods with accuracy, sensitivity, specificity, and AUC-ROC. The global and local explanations are displayed by importance ranking and feature interpretability plots. Results: The five-years prediction accuracy reached 85% (AUC = 0.92) using both cognitive scores and MRI markers. Apart from accuracies, we obtained features’ importance in different follow-up periods. In early stage of AD, the MRI markers play a major role, while for middle-term, the cognitive scores are more important. Feature risk scoring plots demonstrated insightful nonlinear interactive associations between selected factors and outcome. In one-year prediction, lower right inferior temporal volume (<9000) is significantly associated with AD conversion. For two-year prediction, low left inferior temporal thickness (<2) is most critical. For three-year prediction, higher FAQ scores (>4) is the most important. During four-year prediction, APOE4 is the most critical. For five-year prediction, lower right entorhinal volume (<1000) is the most critical feature. Conclusions: The established glass-box model EBMs with multimodal features demonstrated a superior ability with detailed interpretability in predicting AD conversion from MCI. Multi features with significant importance were identified. Further study may be of significance to determine whether the established prediction tool would improve clinical management for AD patients.