Dataset Information

Multimodal prediction of conversion to Alzheimer's disease based on incomplete biomarkers.

ABSTRACT:

Background

This study investigates the prediction of mild cognitive impairment-to-Alzheimer's disease (MCI-to-AD) conversion based on extensive multimodal data with varying degrees of missing values.

Methods

Based on Alzheimer's Disease Neuroimaging Initiative data from MCI-patients including all available modalities, we predicted the conversion to AD within 3 years. Different ways of replacing missing data in combination with different classification algorithms are compared. The performance was evaluated on features prioritized by experts and automatically selected features.

Results

The conversion to AD could be predicted with a maximal accuracy of 73% using support vector machines and features chosen by experts. Among data modalities, neuropsychological, magnetic resonance imaging, and positron emission tomography data were most informative. The best single feature was the functional activities questionnaire.

Conclusion

Extensive multimodal and incomplete data can be adequately handled by a combination of missing data substitution, feature selection, and classification.

SUBMITTER: Ritter K

PROVIDER: S-EPMC4877756 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Multimodal prediction of conversion to Alzheimer's disease based on incomplete biomarkers.

Ritter Kerstin K Schumacher Julia J Weygandt Martin M Buchert Ralph R Allefeld Carsten C Haynes John-Dylan JD

Alzheimer's & dementia (Amsterdam, Netherlands) 20150430 2

<h4>Background</h4>This study investigates the prediction of mild cognitive impairment-to-Alzheimer's disease (MCI-to-AD) conversion based on extensive multimodal data with varying degrees of missing values.<h4>Methods</h4>Based on Alzheimer's Disease Neuroimaging Initiative data from MCI-patients including all available modalities, we predicted the conversion to AD within 3 years. Different ways of replacing missing data in combination with different classification algorithms are compared. The ...[more]

PMID: 27239505

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Project description:Accurately identifying the patients that have mild cognitive impairment (MCI) who will go on to develop Alzheimer's disease (AD) will become essential as new treatments will require identification of AD patients at earlier stages in the disease process. Most previous work in this area has centred around the same automated techniques used to diagnose AD patients from healthy controls, by coupling high dimensional brain image data or other relevant biomarker data to modern machine learning techniques. Such studies can now distinguish between AD patients and controls as accurately as an experienced clinician. Models trained on patients with AD and control subjects can also distinguish between MCI patients that will convert to AD within a given timeframe (MCI-c) and those that remain stable (MCI-s), although differences between these groups are smaller and thus, the corresponding accuracy is lower. The most common type of classifier used in these studies is the support vector machine, which gives categorical class decisions. In this paper, we introduce Gaussian process (GP) classification to the problem. This fully Bayesian method produces naturally probabilistic predictions, which we show correlate well with the actual chances of converting to AD within 3 years in a population of 96 MCI-s and 47 MCI-c subjects. Furthermore, we show that GPs can integrate multimodal data (in this study volumetric MRI, FDG-PET, cerebrospinal fluid, and APOE genotype with the classification process through the use of a mixed kernel). The GP approach aids combination of different data sources by learning parameters automatically from training data via type-II maximum likelihood, which we compare to a more conventional method based on cross validation and an SVM classifier. When the resulting probabilities from the GP are dichotomised to produce a binary classification, the results for predicting MCI conversion based on the combination of all three types of data show a balanced accuracy of 74%. This is a substantially higher accuracy than could be obtained using any individual modality or using a multikernel SVM, and is competitive with the highest accuracy yet achieved for predicting conversion within three years on the widely used ADNI dataset.

Project description:Alzheimer's disease (AD) is a progressive neurodegenerative disorder. It is one of the leading sources of morbidity and mortality in the aging population AD cardinal symptoms include memory and executive function impairment that profoundly alters a patient's ability to perform activities of daily living. People with mild cognitive impairment (MCI) exhibit many of the early clinical symptoms of patients with AD and have a high chance of converting to AD in their lifetime. Diagnostic criteria rely on clinical assessment and brain magnetic resonance imaging (MRI). Many groups are working to help automate this process to improve the clinical workflow. Current computational approaches are focused on predicting whether or not a subject with MCI will convert to AD in the future. To our knowledge, limited attention has been given to the development of automated computer-assisted diagnosis (CAD) systems able to provide an AD conversion diagnosis in MCI patient cohorts followed longitudinally. This is important as these CAD systems could be used by primary care providers to monitor patients with MCI. The method outlined in this paper addresses this gap and presents a computationally efficient pre-processing and prediction pipeline, and is designed for recognizing patterns associated with AD conversion. We propose a new approach that leverages longitudinal data that can be easily acquired in a clinical setting (e.g., T1-weighted magnetic resonance images, cognitive tests, and demographic information) to identify the AD conversion point in MCI subjects with AUC = 84.7. In contrast, cognitive tests and demographics alone achieved AUC = 80.6, a statistically significant difference (n = 669, p < 0.05). We designed a convolutional neural network that is computationally efficient and requires only linear registration between imaging time points. The model architecture combines Attention and Inception architectures while utilizing both cross-sectional and longitudinal imaging and clinical information. Additionally, the top brain regions and clinical features that drove the model's decision were investigated. These included the thalamus, caudate, planum temporale, and the Rey Auditory Verbal Learning Test. We believe our method could be easily translated into the healthcare setting as an objective AD diagnostic tool for patients with MCI.

Project description:Effective fusion of structural magnetic resonance imaging (sMRI) and functional magnetic resonance imaging (fMRI) data has the potential to boost the accuracy of infant age prediction thanks to the complementary information provided by different imaging modalities. However, functional connectivity measured by fMRI during infancy is largely immature and noisy compared to the morphological features from sMRI, thus making the sMRI and fMRI fusion for infant brain analysis extremely challenging. With the conventional multimodal fusion strategies, adding fMRI data for age prediction has a high risk of introducing more noises than useful features, which would lead to reduced accuracy than that merely using sMRI data. To address this issue, we develop a novel model termed as disentangled-multimodal adversarial autoencoder (DMM-AAE) for infant age prediction based on multimodal brain MRI. Specifically, we disentangle the latent variables of autoencoder into common and specific codes to represent the shared and complementary information among modalities, respectively. Then, cross-reconstruction requirement and common-specific distance ratio loss are designed as regularizations to ensure the effectiveness and thoroughness of the disentanglement. By arranging relatively independent autoencoders to separate the modalities and employing disentanglement under cross-reconstruction requirement to integrate them, our DMM-AAE method effectively restrains the possible interference cross modalities, while realizing effective information fusion. Taking advantage of the latent variable disentanglement, a new strategy is further proposed and embedded into DMM-AAE to address the issue of incompleteness of the multimodal neuroimages, which can also be used as an independent algorithm for missing modality imputation. By taking six types of cortical morphometric features from sMRI and brain functional connectivity from fMRI as predictors, the superiority of the proposed DMM-AAE is validated on infant age (35 to 848 days after birth) prediction using incomplete multimodal neuroimages. The mean absolute error of the prediction based on DMM-AAE reaches 37.6 days, outperforming state-of-the-art methods. Generally, our proposed DMM-AAE can serve as a promising model for prediction with multimodal data.

Project description:Alzheimer's disease (AD) is the most common type of dementia. Its diagnosis and progression detection have been intensively studied. Nevertheless, research studies often have little effect on clinical practice mainly due to the following reasons: (1) Most studies depend mainly on a single modality, especially neuroimaging; (2) diagnosis and progression detection are usually studied separately as two independent problems; and (3) current studies concentrate mainly on optimizing the performance of complex machine learning models, while disregarding their explainability. As a result, physicians struggle to interpret these models, and feel it is hard to trust them. In this paper, we carefully develop an accurate and interpretable AD diagnosis and progression detection model. This model provides physicians with accurate decisions along with a set of explanations for every decision. Specifically, the model integrates 11 modalities of 1048 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) real-world dataset: 294 cognitively normal, 254 stable mild cognitive impairment (MCI), 232 progressive MCI, and 268 AD. It is actually a two-layer model with random forest (RF) as classifier algorithm. In the first layer, the model carries out a multi-class classification for the early diagnosis of AD patients. In the second layer, the model applies binary classification to detect possible MCI-to-AD progression within three years from a baseline diagnosis. The performance of the model is optimized with key markers selected from a large set of biological and clinical measures. Regarding explainability, we provide, for each layer, global and instance-based explanations of the RF classifier by using the SHapley Additive exPlanations (SHAP) feature attribution framework. In addition, we implement 22 explainers based on decision trees and fuzzy rule-based systems to provide complementary justifications for every RF decision in each layer. Furthermore, these explanations are represented in natural language form to help physicians understand the predictions. The designed model achieves a cross-validation accuracy of 93.95% and an F1-score of 93.94% in the first layer, while it achieves a cross-validation accuracy of 87.08% and an F1-Score of 87.09% in the second layer. The resulting system is not only accurate, but also trustworthy, accountable, and medically applicable, thanks to the provided explanations which are broadly consistent with each other and with the AD medical literature. The proposed system can help to enhance the clinical understanding of AD diagnosis and progression processes by providing detailed insights into the effect of different modalities on the disease risk.

Dataset Information

Multimodal prediction of conversion to Alzheimer's disease based on incomplete biomarkers.

Background

Methods

Results

Conclusion

Publications

Multimodal prediction of conversion to Alzheimer's disease based on incomplete biomarkers.

Similar Datasets

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