Some forms of mild cognitive impairment (MCI) are the clinical precursors of Alzheimer's disease (AD), while other MCI types tend to remain stable over-time and do not progress to AD. To identify and choose effective and personalized strategies to prevent or slow the progression of AD, we need to develop objective measures that are able to discriminate the MCI patients who are at risk of AD from those MCI patients who have less risk to develop AD. Here, we present a novel deep learning architecture, based on dual learning and an ad hoc layer for 3D separable convolutions, which aims at identifying MCI patients who have a high likelihood of developing AD within 3 years. Our deep learning procedures combine structural magnetic resonance imaging (MRI), demographic, neuropsychological, and APOe4 genetic data as input measures. The most novel characteristics of our machine learning model compared to previous ones are the following: 1) our deep learning model is multi-tasking, in the sense that it jointly learns to simultaneously predict both MCI to AD conversion as well as AD vs. healthy controls classification, which facilitates relevant feature extraction for AD prognostication; 2) the neural network classifier employs fewer parameters than other deep learning architectures which significantly limits data-overfitting (we use ∼550,000 network parameters, which is orders of magnitude lower than other network designs); 3) both structural MRI images and their warp field characteristics, which quantify local volumetric changes in relation to the MRI template, were used as separate input streams to extract as much information as possible from the MRI data. All analyses were performed on a subset of the database made publicly available via the Alzheimer's Disease Neuroimaging Initiative (ADNI), (n = 785 participants, n = 192 AD patients, n = 409 MCI patients (including both MCI patients who convert to AD and MCI patients who do not covert to AD), and n = 184 healthy controls). The most predictive combination of inputs were the structural MRI images and the demographic, neuropsychological, and APOe4 data. In contrast, the warp field metrics were of little added predictive value. The algorithm was able to distinguish the MCI patients developing AD within 3 years from those patients with stable MCI over the same time-period with an area under the curve (AUC) of 0.925 and a 10-fold cross-validated accuracy of 86%, a sensitivity of 87.5%, and specificity of 85%. To our knowledge, this is the highest performance achieved so far using similar datasets. The same network provided an AUC of 1 and 100% accuracy, sensitivity, and specificity when classifying patients with AD from healthy controls. Our classification framework was also robust to the use of different co-registration templates and potentially irrelevant features/image portions. Our approach is flexible and can in principle integrate other imaging modalities, such as PET, and diverse other sets of clinical data. The convolutional framework is potentially applicable to any 3D image dataset and gives the flexibility to design a computer-aided diagnosis system targeting the prediction of several medical conditions and neuropsychiatric disorders via multi-modal imaging and tabular clinical data.
