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

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

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

Tensor-Based Multi-Modality Feature Selection and Regression for Alzheimer's Disease Diagnosis

The assessment of Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) associated with brain changes remains a challenging task. Recent studies have demonstrated that combination of multi-modality imaging techniques can better reflect pathological characteristics and contribute to more accurate diagnosis of AD and MCI. In this paper, we propose a novel tensor-based multi-modality feature selection and regression method for diagnosis and biomarker identification of AD and MCI from normal controls. Specifically, we leverage the tensor structure to exploit high-level correlation information inherent in the multi-modality data, and investigate tensor-level sparsity in the multilinear regression model. We present the practical advantages of our method for the analysis of ADNI data using three imaging modalities (VBM- MRI, FDG-PET and AV45-PET) with clinical parameters of disease severity and cognitive scores. The experimental results demonstrate the superior performance of our proposed method against the state-of-the-art for the disease diagnosis and the identification of disease-specific regions and modality-related differences. The code for this work is publicly available at https://github.com/junfish/BIOS22

Early Identification of Alzheimer’s Disease Using Medical Imaging: A Review From a Machine Learning Approach Perspective

Alzheimer’s disease (AD) is the leading cause of dementia in aged adults, affecting up to 70% of the dementia patients, and posing a serious public health hazard in the twenty-first century. AD is a progressive, irreversible and neuro-degenerative disease with a long pre-clinical period, affecting brain cells leading to memory loss, misperception, learning problems, and improper decisions. Given its significance, presently no treatment options are available, although disease advancement can be retarded through medication. Unfortunately, AD is diagnosed at a very later stage, after irreversible damages to the brain cells have occurred, when there is no scope to prevent further cognitive decline. The use of non-invasive neuroimaging procedures capable of detecting AD at preliminary stages is crucial for providing treatment retarding disease progression, and has stood as a promising area of research. We conducted a comprehensive assessment of papers employing machine learning to predict AD using neuroimaging data. Most of the studies employed brain images from Alzheimer’s disease neuroimaging initiative (ADNI) dataset, consisting of magnetic resonance image (MRI) and positron emission tomography (PET) images. The most widely used method, the support vector machine (SVM), has a mean accuracy of 75.4 percent, whereas convolutional neural networks(CNN) have a mean accuracy of 78.5 percent. Better classification accuracy has been achieved by combining MRI and PET, rather using single neuroimaging technique. Overall, more complicated models, like deep learning, paired with multimodal and multidimensional data (neuroimaging, cognitive, clinical, behavioral and genetic) produced superlative results. However, promising results have been achieved, still there is a room for performance improvement of the proposed methods, providing assistance to healthcare professionals and clinician

Explainable tensor multi-task ensemble learning based on brain structure variation for Alzheimer's disease dynamic prediction

Objective: Machine learning approaches for predicting Alzheimer’s disease (AD) progression can substantially assist researchers and clinicians in developing effective AD preventive and treatment strategies. Methods: This study proposes a novel machine learning algorithm to predict the AD progression utilising a multi-task ensemble learning approach. Specifically, we present a novel tensor multi-task learning (MTL) algorithm based on similarity measurement of spatio-temporal variability of brain biomarkers to model AD progression. In this model, the prediction of each patient sample in the tensor is set as one task, where all tasks share a set of latent factors obtained through tensor decomposition. Furthermore, as subjects have continuous records of brain biomarker testing, the model is extended to ensemble the subjects’ temporally continuous prediction results utilising a gradient boosting kernel to find more accurate predictions. Results: We have conducted extensive experiments utilising data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to evaluate the performance of the proposed algorithm and model. Results demonstrate that the proposed model have superior accuracy and stability in predicting AD progression compared to benchmarks and state-of-the-art multi-task regression methods in terms of the Mini Mental State Examination (MMSE) questionnaire and The Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) cognitive scores. Conclusion: Brain biomarker correlation information can be utilised to identify variations in individual brain structures and the model can be utilised to effectively predict the progression of AD with magnetic resonance imaging (MRI) data and cognitive scores of AD patients at different stages

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

Identifying Associations Between Brain Imaging Phenotypes and Genetic Factors via A Novel Structured SCCA Approach

Brain imaging genetics attracts more and more attention since it can reveal associations between genetic factors and the structures or functions of human brain. Sparse canonical correlation analysis (SCCA) is a powerful bi-multivariate association identification technique in imaging genetics. There have been many SCCA methods which could capture different types of structured imaging genetic relationships. These methods either use the group lasso to recover the group structure, or employ the graph/network guided fused lasso to find out the network structure. However, the group lasso methods have limitation in generalization because of the incomplete or unavailable prior knowledge in real world. The graph/network guided methods are sensitive to the sign of the sample correlation which may be incorrectly estimated. We introduce a new SCCA model using a novel graph guided pairwise group lasso penalty, and propose an efficient optimization algorithm. The proposed method has a strong upper bound for the grouping effect for both positively and negatively correlated variables. We show that our method performs better than or equally to two state-of-the-art SCCA methods on both synthetic and real neuroimaging genetics data. In particular, our method identifies stronger canonical correlations and captures better canonical loading profiles, showing its promise for revealing biologically meaningful imaging genetic associations