Interpretable multivariate survival models: Improving predictions for conversion from mild cognitive impairment to Alzheimer’s disease (AD) via data fusion and machine learning

Accurately predicting which individuals with mild cognitive impairment (MCI) will progress to Alzheimer’s disease (AD) can improve patient care. This study examines the role of quantitative MRI (qMRI), cognitive evaluations, apolipoprotein ε 4 ( APOE ε 4), and cerebrospinal fluid (CSF) biomarkers in Cox survival models to predict progression from MCI to AD. Data from 564 participants in the ADNI study, who transitioned from MCI to AD, were analyzed. The data set included 330 features encompassing qMRI, cognitive assessments, CSF biomarkers, and APOE ε 4 status. Advanced machine learning (ML) methods were applied to evaluate the importance of these data sources, select relevant features, and develop interpretable Cox survival models within a cross-validation framework. The top optimized model achieved a sensitivity of 0.69, 95% CI [0.63, 0.76], and a specificity of 0.87, 95% CI [0.83, 0.90], and used all data sources. The results demonstrated that combining qMRI features with cognitive assessments, CSF biomarkers, and APOE ε 4 status, analyzed using the BSWiMS model, resulted in a substantial improvement in the ability to predict progression from MCI to AD, achieving 81% precission and 87% specificity. These results exceed those obtained with other models evaluated. Finally, biomarker analysis showed that cognitive scores are the most relevant features to predict conversion, followed by CSF and qMRI biomarkers. These findings highlight the value of integrating multiple data sources in highly interpretable Cox survival models for the early identification of individuals at risk for Alzheimer’s disease.