Peter Paul De Deyn

Wenjie Kang, Bo Li, Janne M. Papma et al.

Machine learning methods have shown large potential for the automatic early diagnosis of Alzheimer's Disease (AD). However, some machine learning methods based on imaging data have poor interpretability because it is usually unclear how they make their decisions. Explainable Boosting Machines (EBMs) are interpretable machine learning models based on the statistical framework of generalized additive modeling, but have so far only been used for tabular data. Therefore, we propose a framework that combines the strength of EBM with high-dimensional imaging data using deep learning-based feature extraction. The proposed framework is interpretable because it provides the importance of each feature. We validated the proposed framework on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, achieving accuracy of 0.883 and area-under-the-curve (AUC) of 0.970 on AD and control classification. Furthermore, we validated the proposed framework on an external testing set, achieving accuracy of 0.778 and AUC of 0.887 on AD and subjective cognitive decline (SCD) classification. The proposed framework significantly outperformed an EBM model using volume biomarkers instead of deep learning-based features, as well as an end-to-end convolutional neural network (CNN) with optimized architecture.

Wenjie Kang, Lize Jiskoot, Peter De Deyn et al.

Deep learning methods based on Convolutional Neural Networks (CNNs) have shown great potential to improve early and accurate diagnosis of Alzheimer's disease (AD) dementia based on imaging data. However, these methods have yet to be widely adopted in clinical practice, possibly due to the limited interpretability of deep learning models. The Explainable Boosting Machine (EBM) is a glass-box model but cannot learn features directly from input imaging data. In this study, we propose a novel interpretable model that combines CNNs and EBMs for the diagnosis and prediction of AD. We develop an innovative training strategy that alternatingly trains the CNN component as a feature extractor and the EBM component as the output block to form an end-to-end model. The model takes imaging data as input and provides both predictions and interpretable feature importance measures. We validated the proposed model on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset and the Health-RI Parelsnoer Neurodegenerative Diseases Biobank (PND) as an external testing set. The proposed model achieved an area-under-the-curve (AUC) of 0.956 for AD and control classification, and 0.694 for the prediction of conversion of mild cognitive impairment (MCI) to AD on the ADNI cohort. The proposed model is a glass-box model that achieves a comparable performance with other state-of-the-art black-box models. Our code is publicly available at: https://anonymous.4open.science/r/GL-ICNN.

Esther E. Bron, Stefan Klein, Janne M. Papma et al.

This work validates the generalizability of MRI-based classification of Alzheimer's disease (AD) patients and controls (CN) to an external data set and to the task of prediction of conversion to AD in individuals with mild cognitive impairment (MCI). We used a conventional support vector machine (SVM) and a deep convolutional neural network (CNN) approach based on structural MRI scans that underwent either minimal pre-processing or more extensive pre-processing into modulated gray matter (GM) maps. Classifiers were optimized and evaluated using cross-validation in the ADNI (334 AD, 520 CN). Trained classifiers were subsequently applied to predict conversion to AD in ADNI MCI patients (231 converters, 628 non-converters) and in the independent Health-RI Parelsnoer data set. From this multi-center study representing a tertiary memory clinic population, we included 199 AD patients, 139 participants with subjective cognitive decline, 48 MCI patients converting to dementia, and 91 MCI patients who did not convert to dementia. AD-CN classification based on modulated GM maps resulted in a similar AUC for SVM (0.940) and CNN (0.933). Application to conversion prediction in MCI yielded significantly higher performance for SVM (0.756) than for CNN (0.742). In external validation, performance was slightly decreased. For AD-CN, it again gave similar AUCs for SVM (0.896) and CNN (0.876). For prediction in MCI, performances decreased for both SVM (0.665) and CNN (0.702). Both with SVM and CNN, classification based on modulated GM maps significantly outperformed classification based on minimally processed images. Deep and conventional classifiers performed equally well for AD classification and their performance decreased only slightly when applied to the external cohort. We expect that this work on external validation contributes towards translation of machine learning to clinical practice.