LAUSR

Deep learning (DL) on brain magnetic resonance imaging (MRI) data has shown excellent performance in differentiating individuals with Alzheimer's disease (AD). However, the value of DL in detecting progressive structural MRI (sMRI) abnormalities linked to AD pathology has yet to be established. In this study, an interpretable DL algorithm named the Ensemble of 3‐dimensional convolutional neural network (Ensemble 3DCNN) with enhanced parsing techniques is proposed to investigate the longitudinal trajectories of whole‐brain sMRI changes denoting AD onset and progression. A set of 2369 T1‐weighted images from the multi‐centre Alzheimer's Disease Neuroimaging Initiative and Open Access Series of Imaging Studies cohorts are applied to model derivation, validation, testing, and pattern analysis. An Ensemble‐3DCNN‐based P‐score is generated, based on which multiple brain regions, including amygdala, insular, parahippocampal, and temporal gyrus, exhibit early and connected progressive neurodegeneration. Complex individual variability in the sMRI is also observed. This study combining non‐invasive sMRI and interpretable DL in detecting patterned sMRI changes confirmed AD pathological progression, shedding new light on predicting AD progression using whole‐brain sMRI.