Many classical machine learning techniques have been used to explore Alzheimer's disease (AD), evolving from image decomposition techniques such as principal component analysis toward higher complexity, non-linear decomposition algorithms. With the arrival of the deep learning paradigm, it has become possible to extract high-level abstract features directly from MRI images that internally describe the distribution of data in low-dimensional manifolds. In this work, we try a new exploratory data analysis of AD based on deep convolutional autoencoders. We aim at finding links between cognitive symptoms and the underlying neurodegeneration process by fusing the information of neuropsychological test outcomes, diagnoses, and other clinical data with the imaging features extracted solely via a data-driven decomposition of MRI. The distribution of the extracted features in different combinations is then analyzed and visualized using regression and classification analysis, and the influence of each coordinate of the autoencoder manifold over the brain is estimated. The imaging-derived markers could then predict clinical variables with correlations above 0.6 in the case of neuropsychological evaluation variables such as the MMSE or the ADAS11 scores, achieving a classification accuracy over 80% for the diagnosis of AD.

This paper presents a novel computer-aided diagnosis (CAD) technique for the early diagnosis of the Alzheimer's disease (AD) based on nonnegative matrix factorization (NMF) and support vector machines (SVM) with bounds of confidence. The CAD tool is designed for the study and classification of functional brain images. For this purpose, two different brain image databases are selected: a single photon emission computed tomography (SPECT) database and positron emission tomography (PET) images, both of them containing data for both Alzheimer's disease (AD) patients and healthy controls as a reference. These databases are analyzed by applying the Fisher discriminant ratio (FDR) and nonnegative matrix factorization (NMF) for feature selection and extraction of the most relevant features. The resulting NMF-transformed sets of data, which contain a reduced number of features, are classified by means of a SVM-based classifier with bounds of confidence for decision. The proposed NMF-SVM method yields up to 91% classification accuracy with high sensitivity and specificity rates (upper than 90%). This NMF-SVM CAD tool becomes an accurate method for SPECT and PET AD image classification.