SMAS: Structural MRI-based AD Score using Bayesian supervised VAE

This study introduces the Structural MRI-based Alzheimer's Disease Score (SMAS), a novel index intended to quantify Alzheimer's Disease (AD)-related morphometric patterns using a deep learning Bayesian-supervised Variational Autoencoder (Bayesian-SVAE). The SMAS index was constructed using baseline structural MRI data from the DELCODE study and evaluated longitudinally in two independent cohorts: DELCODE (n=415) and ADNI (n=190). Our findings indicate that SMAS has strong associations with cognitive performance (DELCODE: r=-0.83; ADNI: r=-0.62), age (DELCODE: r=0.50; ADNI: r=0.28), hippocampal volume (DELCODE: r=-0.44; ADNI: r=-0.66), and total gray matter volume (DELCODE: r=-0.42; ADNI: r=-0.47), suggesting its potential as a biomarker for AD-related brain atrophy. Moreover, our longitudinal studies indicated that SMAS may be useful for the early identification and tracking of AD. The model demonstrated significant predictive accuracy in distinguishing cognitively healthy individuals from those with AD (DELCODE: AUC=0.971 at baseline, 0.833 at 36 months; ADNI: AUC=0.817 at baseline, improving to 0.903 at 24 months). Notably, over 36 months, the SMAS index outperformed existing measures such as SPARE-AD and hippocampal volume. The relevance map analysis revealed significant morphological changes in key AD-related brain regions, including the hippocampus, posterior cingulate cortex, precuneus, and lateral parietal cortex, highlighting that SMAS is a sensitive and interpretable biomarker of brain atrophy, suitable for early AD detection and longitudinal monitoring of disease progression.