Multi-modal multi-task learning for joint prediction of multiple regression and classification variables in Alzheimer's disease

Many machine learning and pattern classification methods have been applied to the diagnosis of Alzheimer’s disease (AD) and its prodromal stage, i.e., mild cognitive impairment (MCI). Recently, rather than predicting categorical variables as in classification, several pattern regression methods have also been used to estimate continuous clinical variables from brain images. However, most existing regression methods focus on estimating multiple clinical variables separately and thus cannot utilize the intrinsic useful correlation information among different clinical variables. On the other hand, in those regression methods, only a single modality of data (usually only the structural MRI) is often used, without considering the complementary information that can be provided by different modalities. In this paper, we propose a general methodology, namely Multi-Modal Multi-Task (M3T) learning, to jointly predict multiple variables from multi-modal data. Here, the variables include not only the clinical variables used for regression but also the categorical variable used for classification, with different tasks corresponding to prediction of different variables. Specifically, our method contains two key components, i.e., (1) a multi-task feature selection which selects the common subset of relevant features for multiple variables from each modality, and (2) a multi-modal support vector machine which fuses the above-selected features from all modalities to predict multiple (regression and classification) variables. To validate our method, we perform two sets of experiments on ADNI baseline MRI, FDG-PET, and cerebrospinal fluid (CSF) data from 45 AD patients, 91 MCI patients, and 50 healthy controls (HC). In the first set of experiments, we estimate two clinical variables such as Mini Mental State Examination (MMSE) and Alzheimer’s Disease Assessment Scale - Cognitive Subscale (ADAS-Cog), as well as one categorical variable (with value of ‘AD’, ‘MCI’ or ‘HC’), from the baseline MRI, FDG-PET, and CSF data. In the second set of experiments, we predict the 2-year changes of MMSE and ADAS-Cog scores and also the conversion of MCI to AD from the baseline MRI, FDG-PET, and CSF data. The results on both sets of experiments demonstrate that our proposed M3T learning scheme can achieve better performance on both regression and classification tasks than the conventional learning methods

Label-aligned multi-task feature learning for multimodal classification of Alzheimer’s disease and mild cognitive impairment

Multimodal classification methods using different modalities of imaging and non-imaging data have recently shown great advantages over traditional single-modality-based ones for diagnosis and prognosis of Alzheimer’s disease (AD), as well as its prodromal stage, i.e., mild cognitive impairment (MCI). However, to the best of our knowledge, most existing methods focus on mining the relationship across multiple modalities of the same subjects, while ignoring the potentially useful relationship across different subjects. Accordingly, in this paper, we propose a novel learning method for multimodal classification of AD/MCI, by fully exploring the relationships across both modalities and subjects. Specifically, our proposed method includes two subsequent components, i.e., label-aligned multi-task feature selection and multimodal classification. In the first step, the feature selection learning from multiple modalities are treated as different learning tasks and a group sparsity regularizer is imposed to jointly select a subset of relevant features. Furthermore, to utilize the discriminative information among labeled subjects, a new label-aligned regularization term is added into the objective function of standard multi-task feature selection, where label-alignment means that all multi-modality subjects with the same class labels should be closer in the new feature-reduced space. In the second step, a multi-kernel support vector machine (SVM) is adopted to fuse the selected features from multi-modality data for final classification. To validate our method, we perform experiments on the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database using baseline MRI and FDG-PET imaging data. The experimental results demonstrate that our proposed method achieves better classification performance compared with several state-of-the-art methods for multimodal classification of AD/MCI

Machine Learning for Multiclass Classification and Prediction of Alzheimer\u27s Disease

Alzheimer\u27s disease (AD) is an irreversible neurodegenerative disorder and a common form of dementia. This research aims to develop machine learning algorithms that diagnose and predict the progression of AD from multimodal heterogonous biomarkers with a focus placed on the early diagnosis. To meet this goal, several machine learning-based methods with their unique characteristics for feature extraction and automated classification, prediction, and visualization have been developed to discern subtle progression trends and predict the trajectory of disease progression. The methodology envisioned aims to enhance both the multiclass classification accuracy and prediction outcomes by effectively modeling the interplay between the multimodal biomarkers, handle the missing data challenge, and adequately extract all the relevant features that will be fed into the machine learning framework, all in order to understand the subtle changes that happen in the different stages of the disease. This research will also investigate the notion of multitasking to discover how the two processes of multiclass classification and prediction relate to one another in terms of the features they share and whether they could learn from one another for optimizing multiclass classification and prediction accuracy. This research work also delves into predicting cognitive scores of specific tests over time, using multimodal longitudinal data. The intent is to augment our prospects for analyzing the interplay between the different multimodal features used in the input space to the predicted cognitive scores. Moreover, the power of modality fusion, kernelization, and tensorization have also been investigated to efficiently extract important features hidden in the lower-dimensional feature space without being distracted by those deemed as irrelevant. With the adage that a picture is worth a thousand words, this dissertation introduces a unique color-coded visualization system with a fully integrated machine learning model for the enhanced diagnosis and prognosis of Alzheimer\u27s disease. The incentive here is to show that through visualization, the challenges imposed by both the variability and interrelatedness of the multimodal features could be overcome. Ultimately, this form of visualization via machine learning informs on the challenges faced with multiclass classification and adds insight into the decision-making process for a diagnosis and prognosis

Progression Modeling of Cognitive Disease Using Temporal Data Mining: Research Landscape, Gaps and Solution Design

Dementia is a cognitive disorder whose diagnosis and progression monitoring is very difficult due to a very slow onset and progression. It is difficult to detect whether cognitive decline is due to ageing process or due to some form of dementia as MRI scans of the brain cannot reliably differentiate between ageing related volume loss and pathological changes. Laboratory tests on blood or CSF samples have also not proved very useful. Alzheimer�s disease (AD) is recognized as the most common cause of dementia. Development of sensitive and reliable tool for evaluation in terms of early diagnosis and progression monitoring of AD is required. Since there is an absence of specific markers for predicting AD progression, there is a need to learn more about specific attributes and their temporal relationships that lead to this disease and determine progression from mild cognitive impairment to full blown AD. Various stages of disease and transitions from one stage to the have be modelled based on longitudinal patient data. This paper provides a critical review of the methods to understand disease progression modelling and determine factors leading to progression of AD from initial to final stages. Then the design of a machine learning based solution is proposed to handle the gaps in current research

Identifying Multimodal Intermediate Phenotypes between Genetic Risk Factors and Disease Status in Alzheimer’s Disease

Neuroimaging genetics has attracted growing attention and interest, which is thought to be a powerful strategy to examine the influence of genetic variants (i.e., single nucleotide polymorphisms (SNPs)) on structures or functions of human brain. In recent studies, univariate or multivariate regression analysis methods are typically used to capture the effective associations between genetic variants and quantitative traits (QTs) such as brain imaging phenotypes. The identified imaging QTs, although associated with certain genetic markers, may not be all disease specific. A useful, but underexplored, scenario could be to discover only those QTs associated with both genetic markers and disease status for revealing the chain from genotype to phenotype to symptom. In addition, multimodal brain imaging phenotypes are extracted from different perspectives and imaging markers consistently showing up in multimodalities may provide more insights for mechanistic understanding of diseases (i.e., Alzheimer’s disease (AD)). In this work, we propose a general framework to exploit multi-modal brain imaging phenotypes as intermediate traits that bridge genetic risk factors and multi-class disease status. We applied our proposed method to explore the relation between the well-known AD risk SNP APOE rs429358 and three baseline brain imaging modalities (i.e., structural magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography (FDG-PET) and F-18 florbetapir PET scans amyloid imaging (AV45)) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. The empirical results demonstrate that our proposed method not only helps improve the performances of imaging genetic associations, but also discovers robust and consistent regions of interests (ROIs) across multi-modalities to guide the disease-induced interpretation

MildInt: Deep Learning-Based Multimodal Longitudinal Data Integration Framework

As large amounts of heterogeneous biomedical data become available, numerous methods for integrating such datasets have been developed to extract complementary knowledge from multiple domains of sources. Recently, a deep learning approach has shown promising results in a variety of research areas. However, applying the deep learning approach requires expertise for constructing a deep architecture that can take multimodal longitudinal data. Thus, in this paper, a deep learning-based python package for data integration is developed. The python package deep learning-based multimodal longitudinal data integration framework (MildInt) provides the preconstructed deep learning architecture for a classification task. MildInt contains two learning phases: learning feature representation from each modality of data and training a classifier for the final decision. Adopting deep architecture in the first phase leads to learning more task-relevant feature representation than a linear model. In the second phase, linear regression classifier is used for detecting and investigating biomarkers from multimodal data. Thus, by combining the linear model and the deep learning model, higher accuracy and better interpretability can be achieved. We validated the performance of our package using simulation data and real data. For the real data, as a pilot study, we used clinical and multimodal neuroimaging datasets in Alzheimer's disease to predict the disease progression. MildInt is capable of integrating multiple forms of numerical data including time series and non-time series data for extracting complementary features from the multimodal dataset

Sparse Multi-Response Tensor Regression for Alzheimer's Disease Study With Multivariate Clinical Assessments

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder that has recently seen serious increase in the number of affected subjects. In the last decade, neuroimaging has been shown to be a useful tool to understand AD and its prodromal stage, amnestic mild cognitive impairment (MCI). The majority of AD/MCI studies have focused on disease diagnosis, by formulating the problem as classification with a binary outcome of AD/MCI or healthy controls. There have recently emerged studies that associate image scans with continuous clinical scores that are expected to contain richer information than a binary outcome. However, very few studies aim at modeling multiple clinical scores simultaneously, even though it is commonly conceived that multivariate outcomes provide correlated and complementary information about the disease pathology. In this article, we propose a sparse multi-response tensor regression method to model multiple outcomes jointly as well as to model multiple voxels of an image jointly. The proposed method is particularly useful to both infer clinical scores and thus disease diagnosis, and to identify brain subregions that are highly relevant to the disease outcomes. We conducted experiments on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, and showed that the proposed method enhances the performance and clearly outperforms the competing solutions

Temporally Constrained Group Sparse Learning for Longitudinal Data Analysis in Alzheimer's Disease

Sparse learning has been widely investigated for analysis of brain images to assist the diagnosis of Alzheimer’s disease (AD) and its prodromal stage, i.e., mild cognitive impairment (MCI). However, most existing sparse learning-based studies only adopt cross-sectional analysis methods, where the sparse model is learned using data from a single time-point. Actually, multiple time-points of data are often available in brain imaging applications, which can be used in some longitudinal analysis methods to better uncover the disease progression patterns. Accordingly, in this paper we propose a novel temporally-constrained group sparse learning method aiming for longitudinal analysis with multiple time-points of data. Specifically, we learn a sparse linear regression model by using the imaging data from multiple time-points, where a group regularization term is first employed to group the weights for the same brain region across different time-points together. Furthermore, to reflect the smooth changes between data derived from adjacent time-points, we incorporate two smoothness regularization terms into the objective function, i.e., one fused smoothness term which requires that the differences between two successive weight vectors from adjacent time-points should be small, and another output smoothness term which requires the differences between outputs of two successive models from adjacent time-points should also be small. We develop an efficient optimization algorithm to solve the proposed objective function. Experimental results on ADNI database demonstrate that, compared with conventional sparse learning-based methods, our proposed method can achieve improved regression performance and also help in discovering disease-related biomarkers

Automated detection of Alzheimer disease using MRI images and deep neural networks- A review

Early detection of Alzheimer disease is crucial for deploying interventions and slowing the disease progression. A lot of machine learning and deep learning algorithms have been explored in the past decade with the aim of building an automated detection for Alzheimer. Advancements in data augmentation techniques and advanced deep learning architectures have opened up new frontiers in this field, and research is moving at a rapid speed. Hence, the purpose of this survey is to provide an overview of recent research on deep learning models for Alzheimer disease diagnosis. In addition to categorizing the numerous data sources, neural network architectures, and commonly used assessment measures, we also classify implementation and reproducibility. Our objective is to assist interested researchers in keeping up with the newest developments and in reproducing earlier investigations as benchmarks. In addition, we also indicate future research directions for this topic.Comment: 22 Pages, 5 Figures, 7 Table