Early Prediction of Progression to Alzheimer's Disease using Multi-Modality Neuroimages by a Novel Ordinal Learning Model ADPacer.

Machine learning has shown great promise for integrating multi-modality neuroimaging datasets to predict the risk of progression/conversion to Alzheimer's Disease (AD) for individuals with Mild Cognitive Impairment (MCI). Most existing work aims to classify MCI patients into converters versus non-converters using a pre-defined timeframe. The limitation is a lack of granularity in differentiating MCI patients who convert at different paces. Progression pace prediction has important clinical values, which allow from more personalized interventional strategies, better preparation of patients and their caregivers, and facilitation of patient selection in clinical trials. We proposed a novel ADPacer model which formulated the pace prediction into an ordinal learning problem with a unique capability of leveraging training samples with label ambiguity to augment the training set. This capability differentiates ADPacer from existing ordinal learning algorithms. We applied ADPacer to MCI patient cohorts from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (AIBL), and demonstrated the superior performance of ADPacer compared to existing ordinal learning algorithms. We also integrated the SHapley Additive exPlanations (SHAP) method with ADPacer to assess the contributions from different modalities to the model prediction. The findings are consistent with the AD literature.