Explainable Longitudinal Machine Learning for Dementia Progression Using Cognitive and MRI Biomarkers

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Abstract Dementia is a progressive neurological condition characterized by cognitive decline and structural brain changes that evolve. Longitudinal modeling of these changes is important for improving disease monitoring, identifying progression patterns, and supporting early risk stratification. This study developed an explainable longitudinal machine-learning framework for dementia progression, using cognitive and Magnetic Resonance Imaging (MRI)-derived biomarkers from the Open Access Series of Imaging Studies (OASIS-2) longitudinal dataset. The dataset included 150 subjects and 373 repeated observations classified as Non-demented, Demented, or Converted. Current-visit features, previous-visit features, and slope-based temporal features were constructed from Mini-Mental State Examination, Clinical Dementia Rating, normalized whole-brain volume, estimated total intracranial volume, atlas scaling factor, Age, and MRI delay. Baseline models were compared with a longitudinal gradient-boosted model, using patient-level splitting to reduce data leakage across repeated visits. The proposed longiGradient Gradient boosting model achieved the best held-out test performance, with an accuracy of 88.16%, a macro F1-score of 0.776, and a weighted F1-score of 0.860. The model showed strong classification performance for Demented and Non-demented individuals, while converted cases remained more difficult to identify. A regularized gradient boosting model was also evaluated as an overfitting sensitivity analysis; although it reduced the perfect training fit, it did not improve held-out test performance. Feature importance, permutation importance, and SHapley Additive exPlanations identified Clinical Dementia Rating as the dominant predictor, with slope-based Clinical Dementia Rating providing additional longitudinal information. These findings suggest that combining cognitive measures, MRI-derived biomarkers, and temporal feature engineering can improve dementia progression modeling, although external validation in larger longitudinal cohorts is needed.

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