Early Detection of Alzheimer's Disease Using Explainable Machine Learning on Clinical Biomarkers: A Multi-Class Classification Study Using the Alzheimer's Disease Neuroimaging Initiative (ADNI) Dataset
This work provides an accurate and interpretable tool for early AD detection using routine clinical assessments, addressing the need for accessible screening in clinical settings.
An XGBoost model using eight clinical features from the ADNI dataset achieved near-perfect three-class detection of normal cognition, mild cognitive impairment, and Alzheimer's disease, with a macro AUC of 0.982 and accuracy of 0.943 on a held-out test set.
Background: Alzheimer's disease (AD) affects over 55 million people worldwide. Accurate, interpretable detection of normal cognition (NC), mild cognitive impairment (MCI), and AD from routine clinical assessments remains a critical unmet need. Methods: An XGBoost classifier was developed for three-class detection using eight clinical features from the Alzheimer's Disease Neuroimaging Initiative (ADNI): MMSE, CDR Global, CDR Sum of Boxes (CDR-SB), MoCA, FAQ, age, sex, and education. Hyperparameters were optimised using Optuna (50 trials); class imbalance was addressed with SMOTE. Performance was evaluated by macro AUC-ROC with 1,000-iteration bootstrap 95% confidence intervals, macro F1, balanced accuracy, and Cohen's kappa. SHAP values provided feature-level explainability. Results: The dataset comprised 1,641 baseline subjects (608 NC, 767 MCI, 266 AD). On five-fold cross-validation, mean macro AUC was 0.983 (SD 0.007), accuracy 0.944 (SD 0.006), and macro F1 0.929 (SD 0.008). On the held-out test set (n = 247), macro AUC was 0.982 (95% CI: 0.965--0.995), accuracy 0.943, balanced accuracy 0.932, macro F1 0.927, and Cohen's kappa 0.909. SHAP analysis identified CDR Global as the dominant predictor for NC and MCI, while CDR-SB and MMSE together drove AD classification. Conclusion: An explainable machine learning model trained on routine clinical assessments achieves near-perfect three-class Alzheimer's detection. SHAP analysis reveals clinically plausible, class-specific feature importance patterns supporting clinical validity. Future work will extend this framework with speech biomarkers for multimodal detection.