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

Alzheimer disease (AD) diagnosis and prognosis increasingly rely on machine learning (ML) models. Although these models provide good results, clinical adoption is limited by the need for technical expertise and the lack of trustworthy and consistent model explanations. SHAP (SHapley Additive exPlanations) is com-monly used to interpret AD models, but existing studies tend to focus on explanations for isolated tasks, providing little evidence about their robustness across disease stages, model architectures, or prediction objectives. This paper proposes a multi-level explainability framework that measures the coherence, stabil-ity and consistency of explanations by integrating: (1) within-model coherence metrics between feature importance and SHAP, (2) SHAP stability across AD boundaries, and (3) SHAP cross-task consistency be-tween diagnosis and prognosis. Using AutoML to optimize classifiers on the NACC dataset, we trained four diagnostic and four prognostic models covering the standard AD progression stages. Stability was then evaluated using correlation metrics, top-k feature overlap, SHAP sign consistency, and domain-level contribution ratios. Results show that cognitive and functional markers dominate SHAP explanations in both diagnosis and prognosis. SHAP-SHAP consistency between diagnostic and prognostic models was high across all classifiers, with 100% sign stability and minimal shifts in explanatory magnitude. Domain-level contributions also remained stable, with only minimal increases in genetic features for prognosis. These results demonstrate that SHAP explanations can be quantitatively vali-dated for robustness and transferability, providing clinicians with more reliable interpretations of ML pre-dictions.

Dementia is a major and growing global health burden, with Alzheimer's disease (AD) accounting for most cases. Timely and accurate diagnosis is central to managing this burden and increasingly depends on integrating complementary clinical and imaging information. Multimodal deep learning can combine these modalities for AD diagnosis, but how its explanations behave across modalities, fusion strategies, and cohorts remains unclear. We developed an explainable multimodal framework pairing a 3D CNN encoder for T1-weighted MRI with a feedforward network for harmonized clinical and demographic data, comparing varied model setups on three-way and pairwise diagnostic tasks using 6,479 internal records from the ADNI and 1,703 independent records from the OASIS-3. On ADNI, the tabular-only model achieved the highest three-class AUC-ROC of 0.879 and best discriminated cognitively normal (CN) versus mild cognitive impairment (MCI; 0.903), while cross-attention performed best for MCI versus AD (0.861); CN versus AD was highly discriminative overall. On OASIS-3, the vision-only model performed best (three-class AUC-ROC 0.910); CN versus MCI remained difficult, and no fusion strategy consistently outperformed single modalities across tasks and cohorts. SHAP and Integrated Gradients identified the MMSE as the dominant tabular feature in both cohorts, with global feature rankings agreeing strongly in ADNI ($ρ=0.94$) and OASIS-3 ($ρ=0.96$); CAM-based explanations, however, changed with model configuration and cohort. These findings show that multimodal performance and explanations are task, modality, fusion, and cohort-dependent: a dominant cognitive signal persisted across cohorts, but feature contributions and CAM explanations did not, underscoring the need to evaluate explainability under cohort shift rather than as a stable, intrinsic property.

Alzheimers disease (AD) is a brain disorder that develops slowly and mainly affects memory, thinking, language, and daily activities. It is one of the most common causes of dementia and creates many difficulties for patients as well as their families. In the early stage, the symptoms are often mild and may look like normal ageing. For this reason, many people are diagnosed late, when the disease has already progressed. At present, there is no complete cure for AD. Still, early detection can help doctors manage the condition better and take suitable steps at the right time. In this study, a machine learning model is proposed to detect the early stages of Alzheimers disease using clinical details, neuropsychological test scores, and neuroimaging-related measures. The data used in this work is collected from the Alzheimers Disease Neuroimaging Initiative (ADNI). As the dataset has missing values, iterative imputation is applied to fill them. The dataset also has class imbalance, which is handled using Borderline SVM-SMOTE. After that, feature selection is carried out using wrapper-based and embedded methods so that only important features are used for training. The selected features are divided into training and testing sets, and feature scaling is applied. A stacking ensemble model is developed using Logistic Regression, Extra Trees, Bagging KNN, and LightGBM as base classifiers. Along with this, an artificial neural network is also trained on the same dataset. The performance of these models is compared using precision, recall, F1-score, and AUC-ROC. This study aims to find the best classifier and also identify important biomarkers that may help in the early diagnosis of Alzheimers disease.