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

Applications of neuroimaging to disease-modification trials in Alzheimer's disease.

Critical to development of new therapies for Alzheimer's disease (AD) is the ability to detect clinical or pathological change over time. Clinical outcome measures typically used in therapeutic trials have unfortunately proven to be relatively variable and somewhat insensitive to change in this slowly progressive disease. For this reason, development of surrogate biomarkers that identify significant disease-associated brain changes are necessary to expedite treatment development in AD. Since AD pathology is present in the brain many years prior to clinical manifestation, ideally we want to develop biomarkers of disease that identify abnormal brain structure or function even prior to cognitive decline. Magnetic resonance imaging, fluorodeoxyglucose positron emission tomography, new amyloid imaging techniques, and spinal fluid markers of AD all have great potential to provide surrogate endpoint measures for AD pathology. The Alzheimer's disease neuroimaging initiative (ADNI) was developed for the distinct purpose of evaluating surrogate biomarkers for drug development in AD. Recent evidence from ADNI demonstrates that imaging may provide more sensitive, and earlier, measures of disease progression than traditional clinical measures for powering clinical drug trials in Alzheimer's disease. This review discusses recently presented data from the ADNI dataset, and the importance of imaging in the future of drug development in AD

Improvement of alzheimer disease diagnosis accuracy using ensemble methods

Nowadays, there is a significant increase in the medical data that we should take advantage of that. The application of the machine learning via the data mining processes, such as data classification depends on using a single classification algorithm or those complained as ensemble models. The objective of this work is to improve the classification accuracy of previous results for Alzheimer disease diagnosing. The Decision Tree algorithm with three types of ensemble methods combined, which are Boosting, Bagging and Stacking. The clinical dataset from the Open Access Series of Imaging Studies (OASIS) was used in the experiments. The experimental results of the proposed approach were better than the previous work results. Where the Random Forest (Bagging) achieved the highest accuracy among all algorithms with 90.69%, while the lowest one was Stacking with 79.07%. All these results generated in this paper are higher in accuracy than that done before

Ensemble of random forests One vs. Rest classifiers for MCI and AD prediction using ANOVA cortical and subcortical feature selection and partial least squares.

Background: Alzheimer’s disease (AD) is the most common cause of dementia in the elderly and affects approximately 30 million individuals worldwide. Mild cognitive impairment (MCI) is very frequently a prodromal phase of AD, and existing studies have suggested that people with MCI tend to progress to AD at a rate of about 10 % to 15 % per year. However, the ability of clinicians and machine learning systems to predict AD based on MRI biomarkers at an early stage is still a challenging problem that can have a great impact in improving treatments. Method: The proposed system, developed by the SiPBA-UGR team for this challenge, is based on feature standardization, ANOVA feature selection, partial least squares feature dimension reduction and an ensemble of one vs. rest random forest classifiers. With the aim of improving its performance when discriminating healthy controls (HC) from MCI, a second binary classification level was introduced that reconsiders the HC and MCI predictions of the first level. Results: The system was trained and evaluated on an ADNI datasets that consist of T1-weighted MRI morphological measurements from HC, stable MCI, converter MCI and AD subjects. The proposed system yields a 56.25 % classification score on the test subset which consists of 160 real subjects. Comparison with Existing Method(s): The classifier yielded the best performance when compared to: i) One vs. One (OvO), One vs. Rest (OvR) and error correcting output codes (ECOC) as strategies for reducing the multiclass classification task to multiple binary classification problems, ii) support vector machines, gradient boosting classifier and random forest as base binary classifiers, and iii) bagging ensemble learning. Conclusions: A robust method has been proposed for the international challenge on MCI prediction based on MRI data.This work was supported by the MINECO/FEDER under TEC2015-64718-R project, the Consejería de Economía, Innovacion, Ciencia, y Empleo of the Junta de Andalucía under the P11-TIC-7103 Excellence Project and the Salvador de Madariaga Mobility Grants 2017

Deep Learning for Multiclass Classification, Predictive Modeling and Segmentation of Disease Prone Regions in Alzheimer’s Disease

One of the challenges facing accurate diagnosis and prognosis of Alzheimer’s Disease (AD) is identifying the subtle changes that define the early onset of the disease. This dissertation investigates three of the main challenges confronted when such subtle changes are to be identified in the most meaningful way. These are (1) the missing data challenge, (2) longitudinal modeling of disease progression, and (3) the segmentation and volumetric calculation of disease-prone brain areas in medical images. The scarcity of sufficient data compounded by the missing data challenge in many longitudinal samples exacerbates the problem as we seek statistical meaningfulness in multiclass classification and regression analysis. Although there are many participants in the AD Neuroimaging Initiative (ADNI) study, many of the observations have a lot of missing features which often lead to the exclusion of potentially valuable data points that could add significant meaning in many ongoing experiments. Motivated by the necessity of examining all participants, even those with missing tests or imaging modalities, multiple techniques of handling missing data in this domain have been explored. Specific attention was drawn to the Gradient Boosting (GB) algorithm which has an inherent capability of addressing missing values. Prior to applying state-of-the-art classifiers such as Support Vector Machine (SVM) and Random Forest (RF), the impact of imputing data in common datasets with numerical techniques has been also investigated and compared with the GB algorithm. Furthermore, to discriminate AD subjects from healthy control individuals, and Mild Cognitive Impairment (MCI), longitudinal multimodal heterogeneous data was modeled using recurring neural networks (RNNs). In the segmentation and volumetric calculation challenge, this dissertation places its focus on one of the most relevant disease-prone areas in many neurological and neurodegenerative diseases, the hippocampus region. Changes in hippocampus shape and volume are considered significant biomarkers for AD diagnosis and prognosis. Thus, a two-stage model based on integrating the Vision Transformer and Convolutional Neural Network (CNN) is developed to automatically locate, segment, and estimate the hippocampus volume from the brain 3D MRI. The proposed architecture was trained and tested on a dataset containing 195 brain MRIs from the 2019 Medical Segmentation Decathlon Challenge against the manually segmented regions provided therein and was deployed on 326 MRI from our own data collected through Mount Sinai Medical Center as part of the 1Florida Alzheimer Disease Research Center (ADRC)