In recent years, Alzheimer’s disease (AD) diagnosis using neuroimaging and deep learning has drawn great research attention. However, due to the scarcity of training neuroimaging data, many deep learning models have suffered from severe overfitting. In this study, we propose an ensemble learning framework that combines deep learning and machine learning. The deep learning model was based on a 3D-ResNet to exploit 3D structural features of neuroimaging data. Meanwhile, Extreme Gradient Boosting (XGBoost) machine learning was applied on a voxel-wise basis to draw the most significant voxel groups out of the image. The 3D-ResNet and XGBoost predictions were combined with patient demographics and cognitive test scores (Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR)) to give a final diagnosis prediction. Our proposed method was trained and validated on brain MRI brain images of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset. During the training phase, multiple data augmentation methods were employed to tackle overfitting. Our test set contained only baseline scans, i.e., the first visit scans since we aimed to investigate the ability of our approach in detecting AD during the first visit of AD patients. Our 5-fold cross-validation implementation achieved an average AUC of 100% during training and 96% during testing. Using the same computer, our method was much faster in scoring a prediction, approximately 10 min, than feature extraction-based machine learning methods, which often take many hours to score a prediction. To make the prediction explainable, we visualized the brain MRI image regions that primarily affected the 3D-ResNet model’s prediction via heatmap. Lastly, we observed that proper generation of test sets was critical to avoiding the data leakage issue and ensuring the validity of results.
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