A distributed multitask multimodal approach for the prediction of Alzheimer's disease in a longitudinal study

Predicting the progression of Alzheimer's Disease (AD) has been held back for decades due to the lack of sufficient longitudinal data required for the development of novel machine learning algorithms. This study proposes a novel machine learning algorithm for predicting the progression of Alzheimer's disease using a distributed multimodal, multitask learning method. More specifically, each individual task is defined as a regression model, which predicts cognitive scores at a single time point. Since the prediction tasks for multiple intervals are related to each other in chronological order, multitask regression models have been developed to track the relationship between subsequent tasks. Furthermore, since subjects have various combinations of recording modalities together with other genetic, neuropsychological and demographic risk factors, special attention is given to the fact that each modality may experience a specific sparsity pattern. The model is hence generalized by exploiting multiple individual multitask regression coefficient matrices for each modality. The outcome for each independent modality-specific learner is then integrated with complementary information, known as risk factor parameters, revealing the most prevalent trends of the multimodal data. This new feature space is then used as input to the gradient boosting kernel in search for a more accurate prediction. This proposed model not only captures the complex relationships between the different feature representations, but it also ignores any unrelated information which might skew the regression coefficients. Comparative assessments are made between the performance of the proposed method with several other well-established methods using different multimodal platforms. The results indicate that by capturing the interrelatedness between the different modalities and extracting only relevant information in the data, even in an incomplete longitudinal dataset, will yield minimized prediction errors

Longitudinal Prediction Modeling of Alzheimer Disease using Recurrent Neural Networks

This paper proposes an implementation of Recurrent Neural Networks (RNNs) for (a) predicting future Mini-Mental State Examination (MMSE) scores in a longitudinal study and (b) deploying a multiclass multimodal neuroimaging classification process that involves three different known stages of Alzheimer's progression, cognitively normal (CN), Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD). This multimodal data is fed into two well-studied variations of the RNNs; Long Short-Term Memory (LSTM) and Gated Recurrent Unit (GRU). The accuracy, F-score, sensitivity, and specificity of the models are reported for the classification task as well as the root mean square error (RMSE) and correlation coefficient for the regression task. The results demonstrate the superiority of the proposed model over state-of-the-art classification and regression techniques of Support Vector Machine (SVM), Support Vector Regression (SVR) and Ridge Regression

Prediction Modeling of Alzheimer's Disease and Its Prodromal Stages from Multimodal Data with Missing Values

A major challenge in medical studies, especially those that are longitudinal, is the problem of missing measurements which hinders the effective application of many machine learning algorithms. Furthermore, recent Alzheimer's Disease studies have focused on the delineation of Early Mild Cognitive Impairment (EMCI) and Late Mild Cognitive Impairment (LMCI) from cognitively normal controls (CN) which is essential for developing effective and early treatment methods. To address the aforementioned challenges, this paper explores the potential of using the eXtreme Gradient Boosting (XGBoost) algorithm in handling missing values in multiclass classification. We seek a generalized classification scheme where all prodromal stages of the disease are considered simultaneously in the classification and decision-making processes. Given the large number of subjects (1631) included in this study and in the presence of almost 28% missing values, we investigated the performance of XGBoost on the classification of the four classes of AD, NC, EMCI, and LMCI. Using 10-fold cross validation technique, XGBoost is shown to outperform other state-of-the-art classification algorithms by 3% in terms of accuracy and F-score. Our model achieved an accuracy of 80.52%, a precision of 80.62% and recall of 80.51%, supporting the more natural and promising multiclass classification

A Gaussian-based model for early detection of mild cognitive impairment using multimodal neuroimaging

[Display omitted] •Developing a new probabilistic approach for obtaining the most relevant features from MRI and PET data.•Achieving higher accuracy in diagnosis of the EMCI from CN compared with the previous studies.•The proposed algorithm is able to rank the features based on their importance in every state of Alzheimer’s disease.•Validating the results considering 896 subjects including 296 EMCI subjects as the first study to consider such a large number of EMCI. Diagnosis of early mild cognitive impairment (EMCI) as a prodromal stage of Alzheimer’s disease (AD) with its delineation from the cognitively normal (CN) group remains a challenging but essential step for the planning of early treatment. Although several studies have focused on the MCI diagnosis, this study introduces the early stage of MCI to assess more thoroughly the earliest signs of disease manifestation and progression. We used random forest feature selection model with a Gaussian-based algorithm to perform method evaluation. This integrated method serves to define multivariate normal distributions in order to classify different stages of AD, with the focus placed on detecting EMCI subjects in the most challenging classification of CN vs. EMCI. Using 896 participants classified into the four categories of CN, EMCI, late mild cognitive impairment (LMCI) and AD, the results show that the EMCI group can be delineated from the CN group with a relatively high accuracy of 78.8% and sensitivity of 81.3%. The feature selection model and classifier are compared with some other prominent algorithms. Although higher accuracy has been achieved using the Gaussian process (GP) model (78.8%) over the SVM classifier (75.6%) for CN vs. EMCI classification, with 0.05 being the cutoff for significance, and based on student’s t-test, it was determined that the differences for accuracy, sensitivity, specificity between the GP method and support vector machine (SVM) are not statistically significant. Addressing the challenging classification of CN vs. EMCI provides useful information to help clinicians and researchers determine essential measures that can help in the early detection of AD

A Tensorized Multitask Deep Learning Network for Progression Prediction of Alzheimer’s Disease

With the advances in machine learning for the diagnosis of Alzheimer’s disease (AD), most studies have focused on either identifying the subject’s status through classification algorithms or on predicting their cognitive scores through regression methods, neglecting the potential association between these two tasks. Motivated by the need to enhance the prospects for early diagnosis along with the ability to predict future disease states, this study proposes a deep neural network based on modality fusion, kernelization, and tensorization that perform multiclass classification and longitudinal regression simultaneously within a unified multitask framework. This relationship between multiclass classification and longitudinal regression is found to boost the efficacy of the final model in dealing with both tasks. Different multimodality scenarios are investigated, and complementary aspects of the multimodal features are exploited to simultaneously delineate the subject’s label and predict related cognitive scores at future timepoints using baseline data. The main intent in this multitask framework is to consolidate the highest accuracy possible in terms of precision, sensitivity, F1 score, and area under the curve (AUC) in the multiclass classification task while maintaining the highest similarity in the MMSE score as measured through the correlation coefficient and the RMSE for all time points under the prediction task, with both tasks, run simultaneously under the same set of hyperparameters. The overall accuracy for multiclass classification of the proposed KTMnet method is 66.85 ± 3.77. The prediction results show an average RMSE of 2.32 ± 0.52 and a correlation of 0.71 ± 5.98 for predicting MMSE throughout the time points. These results are compared to state-of-the-art techniques reported in the literature. A discovery from the multitasking of this consolidated machine learning framework is that a set of hyperparameters that optimize the prediction results may not necessarily be the same as those that would optimize the multiclass classification. In other words, there is a breakpoint beyond which enhancing further the results of one process could lead to the downgrading in accuracy for the other

Prediction of Cognitive Test Scores from Variable Length Multimodal Data in Alzheimer's Disease

Alzheimer's disease (AD) is a neurogenerative condition characterized by sharp cognitive decline with no confirmed effective treatment or cure. This makes it critically important to identify the symptoms of Alzheimer's disease in its early stages before significant cognitive deterioration has taken hold and even before any brain morphology and neuropathology are noticeable. In this study, five different multimodal deep neural networks (MDNN), with different architectures, in search of an optimal model for predicting the cognitive test scores for the Mini-Mental State Examination (MMSE) and the modified Alzheimer's Disease Assessment Scale (ADAS-CoG13) over a span of 60 months (5 years). The multimodal data utilized to train and test the proposed models were obtained from the Alzheimer's Disease Neuroimaging Initiative study and includes cerebrospinal fluid (CSF) levels of tau and beta-amyloid, structural measures from magnetic resonance imaging (MRI), functional and metabolic measures from positron emission tomography (PET), and cognitive scores from the neuropsychological tests (Cog). The models developed herein delve into two main issues: (1) application merits of single-task vs. multitask for predicting future cognitive scores and (2) whether time-varying input data are better suited than specific timepoints for optimizing prediction results. This model yields a high of 90.27% (SD = 1.36) prediction accuracy (correlation) at 6 months after the initial visit to a lower 79.91% (SD = 8.84) prediction accuracy at 60 months. The analysis provided is comprehensive as it determines the predictions at all other timepoints and all MDNN models include converters in the CN and MCI groups (CNc, MCIc) and all the unstable groups in the CN and MCI groups (CNun and MCIun) that reverted to CN from MCI and to MCI from AD, so as not to bias the results. The results show that the best performance is achieved by a multimodal combined single-task long short-term memory (LSTM) regressor with an input sequence length of 2 data points (2 visits, 6 months apart) augmented with a pretrained Neural Network Estimator to fill in for the missing values