Deep Learning Approaches with Explainable AI for Differentiating Alzheimer’s Disease and Mild Cognitive Impairment

Early and accurate diagnosis of Alzheimer’s disease is critical for effective clinical intervention, particularly in distinguishing it from mild cognitive impairment, a prodromal stage marked by subtle structural changes. In this study, we propose a hybrid deep learning ensemble framework for Alzheimer’s disease classification using structural magnetic resonance imaging. Gray and white matter slices are used as inputs to three pretrained convolutional neural networks: ResNet50, NASNet, and MobileNet, each fine-tuned through an end-to-end process. To further enhance performance, we incorporate a stacked ensemble learning strategy with a meta-learner and weighted averaging to optimally combine the base models. Evaluated on the Alzheimer’s Disease Neuroimaging Initiative dataset, the proposed method achieves state-of-the-art accuracy of 99.21% for Alzheimer’s disease vs. mild cognitive impairment and 91.02% for mild cognitive impairment vs. normal controls, outperforming conventional transfer learning and baseline ensemble methods. To improve interpretability in image-based diagnostics, we integrate Explainable AI techniques by Gradient-weighted Class Activation Mapping, which generates heatmaps and attribution maps that highlight critical regions in gray and white matter slices, revealing structural biomarkers that influence model decisions. These results highlight the framework’s potential for robust and scalable clinical decision support in neurodegenerative disease diagnostics.