Prediction Of Mild Cognitive Impairment Conversion Research Articles

A transformer-based unified multimodal framework for Alzheimer's disease assessment

In Alzheimer's disease (AD) assessment, traditional deep learning approaches have often employed separate methodologies to handle the diverse modalities of input data. Recognizing the critical need for a cohesive and interconnected analytical framework, we propose the AD-Transformer, a novel transformer-based unified deep learning model. This innovative framework seamlessly integrates structural magnetic resonance imaging (sMRI), clinical, and genetic data from the extensive Alzheimer's Disease Neuroimaging Initiative (ADNI) database, encompassing 1651 subjects. By employing a Patch-CNN block, the AD-Transformer efficiently transforms image data into image tokens, while a linear projection layer adeptly converts non-image data into corresponding tokens. As the core, a transformer block learns comprehensive representations of the input data, capturing the intricate interplay between modalities. The AD-Transformer sets a new benchmark in AD diagnosis and Mild Cognitive Impairment (MCI) conversion prediction, achieving remarkable average area under curve (AUC) values of 0.993 and 0.845, respectively, surpassing those of traditional image-only models and non-unified multimodal models. Our experimental results confirmed the potential of the AD-Transformer as a potent tool in AD diagnosis and MCI conversion prediction. By providing a unified framework that jointly learns holistic representations of both image and non-image data, the AD-Transformer paves the way for more effective and precise clinical assessments, offering a clinically adaptable strategy for leveraging diverse data modalities in the battle against AD.

Predicting conversion from mild cognitive impairment to Alzheimer's disease: a multimodal approach.

Successively predicting whether mild cognitive impairment patients will progress to Alzheimer's disease is of significant clinical relevance. This ability may provide information that can be leveraged by emerging intervention approaches and thus mitigate some of the negative effects of the disease. Neuroimaging biomarkers have gained some attention in recent years and may be useful in predicting the conversion of mild cognitive impairment to Alzheimer's disease. We implemented a novel multi-modal approach that allowed us to evaluate the potential of different imaging modalities, both alone and in different degrees of combinations, in predicting the conversion to Alzheimer's disease of mild cognitive impairment patients. We applied this approach to the imaging data from the Alzheimer's Disease Neuroimaging Initiative that is a multi-modal imaging dataset comprised of MRI, Fluorodeoxyglucose PET, Florbetapir PET and diffusion tensor imaging. We included a total of 480 mild cognitive impairment patients that were split into two groups: converted and stable. Imaging data were segmented into atlas-based regions of interest, from which relevant features were extracted for the different imaging modalities and used to construct machine-learning models to classify mild cognitive impairment patients into converted or stable, using each of the different imaging modalities independently. The models were then combined, using a simple weight fusion ensemble strategy, to evaluate the complementarity of different imaging modalities and their contribution to the prediction accuracy of the models. The single-modality findings revealed that the model, utilizing features extracted from Florbetapir PET, demonstrated the highest performance with a balanced accuracy of 83.51%. Concerning multi-modality models, not all combinations enhanced mild cognitive impairment conversion prediction. Notably, the combination of MRI with Fluorodeoxyglucose PET emerged as the most promising, exhibiting an overall improvement in predictive capabilities, achieving a balanced accuracy of 78.43%. This indicates synergy and complementarity between the two imaging modalities in predicting mild cognitive impairment conversion. These findings suggest that β-amyloid accumulation provides robust predictive capabilities, while the combination of multiple imaging modalities has the potential to surpass certain single-modality approaches. Exploring modality-specific biomarkers, we identified the brainstem as a sensitive biomarker for both MRI and Fluorodeoxyglucose PET modalities, implicating its involvement in early Alzheimer's pathology. Notably, the corpus callosum and adjacent cortical regions emerged as potential biomarkers, warranting further study into their role in the early stages of Alzheimer's disease.

An interpretable Alzheimer's disease oligogenic risk score informed by neuroimaging biomarkers improves risk prediction and stratification.

Stratification of Alzheimer's disease (AD) patients into risk subgroups using Polygenic Risk Scores (PRS) presents novel opportunities for the development of clinical trials and disease-modifying therapies. However, the heterogeneous nature of AD continues to pose significant challenges for the clinical broadscale use of PRS. PRS remains unfit in demonstrating sufficient accuracy in risk prediction, particularly for individuals with mild cognitive impairment (MCI), and in allowing feasible interpretation of specific genes or SNPs contributing to disease risk. We propose adORS, a novel oligogenic risk score for AD, to better predict risk of disease by using an optimized list of relevant genetic risk factors. Using whole genome sequencing data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort (n = 1,545), we selected 20 genes that exhibited the strongest correlations with FDG-PET and AV45-PET, recognized neuroimaging biomarkers that detect functional brain changes in AD. This subset of genes was incorporated into adORS to assess, in comparison to PRS, the prediction accuracy of CN vs. AD classification and MCI conversion prediction, risk stratification of the ADNI cohort, and interpretability of the genetic information included in the scores. adORS improved AUC scores over PRS in both CN vs. AD classification and MCI conversion prediction. The oligogenic model also refined risk-based stratification, even without the assistance of APOE, thus reflecting the true prevalence rate of the ADNI cohort compared to PRS. Interpretation analysis shows that genes included in adORS, such as ATF6, EFCAB11, ING5, SIK3, and CD46, have been observed in similar neurodegenerative disorders and/or are supported by AD-related literature. Compared to conventional PRS, adORS may prove to be a more appropriate choice of differentiating patients into high or low genetic risk of AD in clinical studies or settings. Additionally, the ability to interpret specific genetic information allows the focus to be shifted from general relative risk based on a given population to the information that adORS can provide for a single individual, thus permitting the possibility of personalized treatments for AD.

Deep joint learning of pathological region localization and Alzheimer’s disease diagnosis

The identification of Alzheimer’s disease (AD) using structural magnetic resonance imaging (sMRI) has been studied based on the subtle morphological changes in the brain. One of the typical approaches is a deep learning-based patch-level feature representation. For this approach, however, the predetermined patches before learning the diagnostic model can limit classification performance. To mitigate this problem, we propose the BrainBagNet with a position-based gate (PG), which applies position information of brain images represented through the 3D coordinates. Our proposed method represents the patch-level class evidence based on both MR scan and position information for image-level prediction. To validate the effectiveness of our proposed framework, we conducted comprehensive experiments comparing it with state-of-the-art methods, utilizing two publicly available datasets: the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the Australian Imaging, Biomarkers and Lifestyle (AIBL) dataset. Furthermore, our experimental results demonstrate that our proposed method outperforms the existing competing methods in terms of classification performance for both AD diagnosis and mild cognitive impairment conversion prediction tasks. In addition, we performed various analyses of the results from diverse perspectives to obtain further insights into the underlying mechanisms and strengths of our proposed framework. Based on the results of our experiments, we demonstrate that our proposed framework has the potential to advance deep-learning-based patch-level feature representation studies for AD diagnosis and MCI conversion prediction. In addition, our method provides valuable insights, such as interpretability, and the ability to capture subtle changes, into the underlying pathological processes of AD and MCI, benefiting both researchers and clinicians.

Population-based GCN method for diagnosis of Alzheimer's disease using brain metabolic or volumetric features

As a deep learning method, graph convolution network (GCN) has the advantage of dealing with non-Euclidean domain problems and is constantly applied in the research of computer-aided diagnosis of Alzheimer's disease (AD). In graph-based methods for AD diagnosis, nodes can represent potential subjects with a set of vectors, and edges combine the interaction and similarity between subjects. However, for the three-dimensional neuroimage like structural Magnetic Resonance Imaging (sMRI) or Positron Emission Tomography (PET), due to the non-sequential of ROI (Region of Interest) features (compared with four-dimensional neuroimage), which makes the graph-based analysis approach more difficult. In this study, we obtained individual features by constructing brain network via health group indirectly, and then constructed a population-based GCN framework by expressing the subject population as adjacency matrix in graph to achieve the diagnosis of AD. The nodes in graph are associated with individual features, and edges are weighted by combining the phenotypic information, we further discuss the influence of phenotypic information on the classification performance of GCN. Compared with acquiring the ROI features of the brain regions as the input features of GCN, our proposed method remarkably improved the prediction accuracy based on both sMRI and PET images by about 5 to 10 percentage. Through our testing and experimental analysis on the public ADNI dataset, our method achieved improved performance for AD diagnosis and mild cognitive impairment conversion prediction tasks. Our proposed method also provides technical support for AD diagnosis using GCN method based on three-dimensional brain images.

End-to-end automatic pathology localization for Alzheimer’s disease diagnosis using structural MRI

Structural magnetic resonance imaging (sMRI) is an essential part of the clinical assessment of patients at risk of Alzheimer dementia. One key challenge in sMRI-based computer-aided dementia diagnosis is to localize local pathological regions for discriminative feature learning. Existing solutions predominantly depend on generating saliency maps for pathology localization and handle the localization task independently of the dementia diagnosis task, leading to a complex multi-stage training pipeline that is hard to optimize with weakly-supervised sMRI-level annotations. In this work, we aim to simplify the pathology localization task and construct an end-to-end automatic localization framework (AutoLoc) for Alzheimer’s disease diagnosis. To this end, we first present an efficient pathology localization paradigm that directly predicts the coordinate of the most disease-related region in each sMRI slice. Then, we approximate the non-differentiable patch-cropping operation with the bilinear interpolation technique, which eliminates the barrier to gradient backpropagation and thus enables the joint optimization of localization and diagnosis tasks. Extensive experiments on commonly used ADNI and AIBL datasets demonstrate the superiority of our method. Especially, we achieve 93.38% and 81.12% accuracy on Alzheimer’s disease classification and mild cognitive impairment conversion prediction tasks, respectively. Several important brain regions, such as rostral hippocampus and globus pallidus, are identified to be highly associated with Alzheimer’s disease.

Vision transformers for the prediction of mild cognitive impairment to Alzheimer's disease progression using mid-sagittal sMRI.

Alzheimer's disease (AD) is one of the most common causes of neurodegenerative disease affecting over 50 million people worldwide. However, most AD diagnosis occurs in the moderate to late stage, which means that the optimal time for treatment has already passed. Mild cognitive impairment (MCI) is an intermediate state between cognitively normal people and AD patients. Therefore, the accurate prediction in the conversion process of MCI to AD may allow patients to start preventive intervention to slow the progression of the disease. Nowadays, neuroimaging techniques have been developed and are used to determine AD-related structural biomarkers. Deep learning approaches have rapidly become a key methodology applied to these techniques to find biomarkers. In this study, we aimed to investigate an MCI-to-AD prediction method using Vision Transformers (ViT) to structural magnetic resonance images (sMRI). The Alzheimer's Disease Neuroimaging Initiative (ADNI) database containing 598 MCI subjects was used to predict MCI subjects' progression to AD. There are three main objectives in our study: (i) to propose an MRI-based Vision Transformers approach for MCI to AD progression classification, (ii) to evaluate the performance of different ViT architectures to obtain the most advisable one, and (iii) to visualize the brain region mostly affect the prediction of deep learning approach to MCI progression. Our method achieved state-of-the-art classification performance in terms of accuracy (83.27%), specificity (85.07%), and sensitivity (81.48%) compared with a set of conventional methods. Next, we visualized the brain regions that mostly contribute to the prediction of MCI progression for interpretability of the proposed model. The discriminative pathological locations include the thalamus, medial frontal, and occipital-corroborating the reliability of our model. In conclusion, our methods provide an effective and accurate technique for the prediction of MCI conversion to AD. The results obtained in this study outperform previous reports using the ADNI collection, and it suggests that sMRI-based ViT could be efficiently applied with a considerable potential benefit for AD patient management. The brain regions mostly contributing to prediction, in conjunction with the identified anatomical features, will support the building of a robust solution for other neurodegenerative diseases in future.

MCI Conversion Prediction Using 3D Zernike Moments and the Improved Dynamic Particle Swarm Optimization Algorithm

Mild cognitive impairment (MCI) conversion prediction is a vital challenge in the area of Alzheimer’s disease (AD) as it could determine possible treatment pathways for AD patients. In this work, we presented a robust MCI conversion prediction framework based on the 3D-Zernike Moment (3D-ZM) method that generates statistical features (e.g., shape, texture, and symmetry information) from 3D-MRI scans and improved dynamic particle swarm optimization (IDPSO) that finds an informative sub-set of Zernike features for MCI conversion prediction. We quantified the efficiency of the proposed prediction framework on a large sample of MCI patients including 105 progressive-MCI (pMCI) and 121 stable-MCI (sMCI) at the baseline from the ADNI dataset. Using the proposed MCI conversion prediction framework, pMCI patients were distinguished from sMCI patients with an accuracy exceeding 75% (sensitivity, 83%, and specificity, 68%), which is well comparable with the state-of-the-art MCI conversion prediction approaches. Experimental results indicate that the 3D-ZM method can represent informative statistical patterns from 3D-MRI scans and IDPSO has a great capability to find meaningful statistical features for identifying MCI patients who are at risk of conversion to the AD stage.

Class activation attention transfer neural networks for MCI conversion prediction

Accurate prediction of the trajectory of Alzheimer’s disease (AD) from an early stage is of substantial value for treatment and planning to delay the onset of AD. We propose a novel attention transfer method to train a 3D convolutional neural network to predict which patients with mild cognitive impairment (MCI) will progress to AD within 3 years. A model is first trained on a separate but related source task (task we are transferring information from) to automatically learn regions of interest (ROI) from a given image. Next we train a model to simultaneously classify progressive MCI (pMCI) and stable MCI (sMCI) (the target task we want to solve) and the ROIs learned from the source task. The predicted ROIs are then used to focus the model’s attention on certain areas of the brain when classifying pMCI versus sMCI. Thus, in contrast to traditional transfer learning, we transfer attention maps instead of transferring model weights from a source task to the target classification task. Our Method outperformed all methods tested including traditional transfer learning and methods that used expert knowledge to define ROI. Furthermore, the attention map transferred from the source task highlights known Alzheimer’s pathology.

Predicting the pace of MCI progression to AD based on multi‐modality neuroimaging data by a novel hybrid ordinal learning algorithm

AbstractBackgroundMachine learning (ML) has shown great promise for integrating multi‐modality neuroimaging datasets to predict the risk of converting to AD for individuals with Mild Cognitive Impairment (MCI). Most existing work aims to classify MCI patients into converters versus non‐converters. The limitation is a lack of granularity in differentiating MCI patients who convert at different paces. Pace prediction has important clinical values by allowing for more personalized interventional strategies, better preparing patients and their caregivers, and facilitating patient selection in clinical trials. We proposed a novel Hybrid Ordinal Learning (HOL) algorithm for pace prediction of MCI conversion to AD.MethodThis study focused on the amyloid‐positive MCI patient cohort in ADNI for the pace prediction, which included 282 samples. The datasets included baseline T1‐MRI, amyloid‐PET, MMSE, CDR, age, gender, years of education, and APOE status. ROI‐based structural measures were computed from T1‐MRI using FreeSurfer v7.1 and regional SUVR measures were computed using our in‐house pipeline from amyloid‐PET. HOL was trained to predict the conversion to AD for each MCI patient into four ordinal classes representing four fast‐to‐slow paces of conversion, e.g., conversion in the first year, not in the first but in the second year, not in the first two years but by the fifth year, and not in the first five years, respectively. The novelty of HOL compared to existing ordinal classification algorithms was its capability of leveraging imperfectly‐labeled samples in the training set to build a robust learner.ResultUnder cross validation, HOL achieved 0.83 accuracy, balanced across the different paces, based on a combination of 314 features from MRI, PET, and clinical data, while the conventional ordinal SVM classifier achieved only 0.68 accuracy.ConclusionWe demonstrated that a novel ML algorithm, HOC, could achieve a high accuracy in predicting the pace of conversion to AD for MCI patients. Future research is needed to validate the research finding with larger datasets.

Ensemble of convolutional neural networks and multilayer perceptron for the diagnosis of mild cognitive impairment and Alzheimer's disease.

Structural magnetic resonance imaging (sMRI) can provide morphological information about the structure and function of the brain in the same scanning process. It has been widely used in the diagnosis of Alzheimer's disease (AD) and mild cognitive impairment (MCI). To capture the anatomical changes in the brain caused by AD/MCI, deep learning-based MRI image analysis methods have been proposed in recent years. However, it is observed that the performance of most existing methods is limited as they only construct a single type of deep network and ignore the significance of other clinicalinformation. To make up for these defects, an ensemble framework that incorporates three types of dedicatedly-designed convolutional neural networks (CNNs) and a multilayer perceptron (MLP) network is proposed, where three CNNs with entropy-based multi-instance learning pooling layers have more reliable feature selection abilities. The dedicatedly-designed base classifiers can make use of the heterogeneous data, and empower the framework with enhanced diversity and robustness. In particular, to consider the interactions among the base classifiers, a novel multi-head self-attention voting scheme is designed. Moreover, considering the chance that MCI can be transformed to AD, the proposed framework is designed to diagnose AD and predict MCI conversion simultaneously, with the aid of the transfer learning technique. For performance evaluation and comparison, extensive experiments are conducted on the public dataset of the Alzheimer's Disease Neuroimaging Initiative (ADNI). The results show that the proposed ensemble framework provides superior performance under most of the evaluation metrics. Especially, the proposed framework achieves state-of-the-art diagnostic accuracy (98.61% for the AD diagnosis task, and 84.49% for the MCI conversion prediction task). These promising results demonstrate the proposed ensemble framework can accurately diagnose AD patients and predict the conversion of MCI patients, which has the potential of clinical practice for diagnosing AD andMCI.

Disease-Image-Specific Learning for Diagnosis-Oriented Neuroimage Synthesis With Incomplete Multi-Modality Data.

Incomplete data problem is commonly existing in classification tasks with multi-source data, particularly the disease diagnosis with multi-modality neuroimages, to track which, some methods have been proposed to utilize all available subjects by imputing missing neuroimages. However, these methods usually treat image synthesis and disease diagnosis as two standalone tasks, thus ignoring the specificity conveyed in different modalities, i.e., different modalities may highlight different disease-relevant regions in the brain. To this end, we propose a disease-image-specific deep learning (DSDL) framework for joint neuroimage synthesis and disease diagnosis using incomplete multi-modality neuroimages. Specifically, with each whole-brain scan as input, we first design a Disease-image-Specific Network (DSNet) with a spatial cosine module to implicitly model the disease-image specificity. We then develop a Feature-consistency Generative Adversarial Network (FGAN) to impute missing neuroimages, where feature maps (generated by DSNet) of a synthetic image and its respective real image are encouraged to be consistent while preserving the disease-image-specific information. Since our FGAN is correlated with DSNet, missing neuroimages can be synthesized in a diagnosis-oriented manner. Experimental results on three datasets suggest that our method can not only generate reasonable neuroimages, but also achieve state-of-the-art performance in both tasks of Alzheimer's disease identification and mild cognitive impairment conversion prediction.

A transformer-based multi-features fusion model for prediction of conversion in mild cognitive impairment.

Mild cognitive impairment (MCI) is usually considered the early stage of Alzheimer's disease (AD). Therefore, the accurate identification of MCI individuals with high risk in converting to AD is essential for the potential prevention and treatment of AD. Recently, the great success of deep learning has sparked interest in applying deep learning to neuroimaging field. However, deep learning techniques are prone to overfitting since available neuroimaging datasets are not sufficiently large. Therefore, we proposed a deep learning model fusing cortical features to address the issue of fusion and classification blocks. To validate the effectiveness of the proposed model, we compared seven different models on the same dataset in the literature. The results show that our proposed model outperformed the competing models in the prediction of MCI conversion with an accuracy of 83.3% in the testing dataset. Subsequently, we used deep learning to characterize the contribution of brain regions and different cortical features to MCI progression. The results revealed that the caudal anterior cingulate and pars orbitalis contributed most to the classification task, and our model pays more attention to volume features and cortical thickness features.

Assessing clinical progression from subjective cognitive decline to mild cognitive impairment with incomplete multi-modal neuroimages.

Accurately assessing clinical progression from subjective cognitive decline (SCD) to mild cognitive impairment (MCI) is crucial for early intervention of pathological cognitive decline. Multi-modal neuroimaging data such as T1-weighted magnetic resonance imaging (MRI) and positron emission tomography (PET), help provide objective and supplementary disease biomarkers for computer-aided diagnosis of MCI. However, there are few studies dedicated to SCD progression prediction since subjects usually lack one or more imaging modalities. Besides, one usually has a limited number (e.g., tens) of SCD subjects, negatively affecting model robustness. To this end, we propose a Joint neuroimage Synthesis and Representation Learning (JSRL) framework for SCD conversion prediction using incomplete multi-modal neuroimages. The JSRL contains two components: 1) a generative adversarial network to synthesize missing images and generate multi-modal features, and 2) a classification network to fuse multi-modal features for SCD conversion prediction. The two components are incorporated into a joint learning framework by sharing the same features, encouraging effective fusion of multi-modal features for accurate prediction. A transfer learning strategy is employed in the proposed framework by leveraging model trained on the Alzheimer's Disease Neuroimaging Initiative (ADNI) with MRI and fluorodeoxyglucose PET from 863 subjects to both the Chinese Longitudinal Aging Study (CLAS) with only MRI from 76 SCD subjects and the Australian Imaging, Biomarkers and Lifestyle (AIBL) with MRI from 235 subjects. Experimental results suggest that the proposed JSRL yields superior performance in SCD and MCI conversion prediction and cross-database neuroimage synthesis, compared with several state-of-the-art methods.

A parallel attention-augmented bilinear network for early magnetic resonance imaging-based diagnosis of Alzheimer's disease.

Structural magnetic resonance imaging (sMRI) can capture the spatial patterns of brain atrophy in Alzheimer's disease (AD) and incipient dementia. Recently, many sMRI‐based deep learning methods have been developed for AD diagnosis. Some of these methods utilize neural networks to extract high‐level representations on the basis of handcrafted features, while others attempt to learn useful features from brain regions proposed by a separate module. However, these methods require considerable manual engineering. Their stepwise training procedures would introduce cascading errors. Here, we propose the parallel attention‐augmented bilinear network, a novel deep learning framework for AD diagnosis. Based on a 3D convolutional neural network, the framework directly learns both global and local features from sMRI scans without any prior knowledge. The framework is lightweight and suitable for end‐to‐end training. We evaluate the framework on two public datasets (ADNI‐1 and ADNI‐2) containing 1,340 subjects. On both the AD classification and mild cognitive impairment conversion prediction tasks, our framework achieves competitive results. Furthermore, we generate heat maps that highlight discriminative areas for visual interpretation. Experiments demonstrate the effectiveness of the proposed framework when medical priors are unavailable or the computing resources are limited. The proposed framework is general for 3D medical image analysis with both efficiency and interpretability.

MRI-based Alzheimer’s disease prediction via distilling the knowledge in multi-modal data

Mild cognitive impairment (MCI) conversion prediction, i.e., identifying MCI patients of high risks converting to Alzheimer’s disease (AD), is essential for preventing or slowing the progression of AD. Although previous studies have shown that the fusion of multi-modal data can effectively improve the prediction accuracy, their applications are largely restricted by the limited availability or high cost of multi-modal data. Building an effective prediction model using only magnetic resonance imaging (MRI) remains a challenging research topic. In this work, we propose a multi-modal multi-instance distillation scheme, which aims to distill the knowledge learned from multi-modal data to an MRI-based network for MCI conversion prediction. In contrast to existing distillation algorithms, the proposed multi-instance probabilities demonstrate a superior capability of representing the complicated atrophy distributions, and can guide the MRI-based network to better explore the input MRI. To our best knowledge, this is the first study that attempts to improve an MRI-based prediction model by leveraging extra supervision distilled from multi-modal information. Experiments demonstrate the advantage of our framework, suggesting its potentials in the data-limited clinical settings.

Biomarker Extraction Based on Subspace Learning for the Prediction of Mild Cognitive Impairment Conversion.

Accurate recognition of progressive mild cognitive impairment (MCI) is helpful to reduce the risk of developing Alzheimer's disease (AD). However, it is still challenging to extract effective biomarkers from multivariate brain structural magnetic resonance imaging (MRI) features to accurately differentiate the progressive MCI from stable MCI. We develop novel biomarkers by combining subspace learning methods with the information of AD as well as normal control (NC) subjects for the prediction of MCI conversion using multivariate structural MRI data. Specifically, we first learn two projection matrices to map multivariate structural MRI data into a common label subspace for AD and NC subjects, where the original data structure and the one-to-one correspondence between multiple variables are kept as much as possible. Afterwards, the multivariate structural MRI features of MCI subjects are mapped into a common subspace according to the projection matrices. We then perform the self-weighted operation and weighted fusion on the features in common subspace to extract the novel biomarkers for MCI subjects. The proposed biomarkers are tested on Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. Experimental results indicate that our proposed biomarkers outperform the competing biomarkers on the discrimination between progressive MCI and stable MCI. And the improvement from the proposed biomarkers is not limited to a particular classifier. Moreover, the results also confirm that the information of AD and NC subjects is conducive to predicting conversion from MCI to AD. In conclusion, we find a good representation of brain features from high-dimensional MRI data, which exhibits promising performance for predicting conversion from MCI to AD.

Modularity-Guided Functional Brain Network Analysis for Early-Stage Dementia Identification.

Function brain network (FBN) analysis has shown great potential in identifying brain diseases, such as Alzheimer's disease (AD) and its prodromal stage, namely mild cognitive impairment (MCI). It is essential to identify discriminative and interpretable features from function brain networks, so as to improve classification performance and help us understand the pathological mechanism of AD-related brain disorders. Previous studies usually extract node statistics or edge weights from FBNs to represent each subject. However, these methods generally ignore the topological structure (such as modularity) of FBNs. To address this issue, we propose a modular-LASSO feature selection (MLFS) framework that can explicitly model the modularity information to identify discriminative and interpretable features from FBNs for automated AD/MCI classification. Specifically, the proposed MLFS method first searches the modular structure of FBNs through a signed spectral clustering algorithm, and then selects discriminative features via a modularity-induced group LASSO method, followed by a support vector machine (SVM) for classification. To evaluate the effectiveness of the proposed method, extensive experiments are performed on 563 resting-state functional MRI scans from the public ADNI database to identify subjects with AD/MCI from normal controls and predict the future progress of MCI subjects. Experimental results demonstrate that our method is superior to previous methods in both tasks of AD/MCI identification and MCI conversion prediction, and also helps discover discriminative brain regions and functional connectivities associated with AD.

Transfer learning for predicting conversion from mild cognitive impairment to dementia of Alzheimer's type based on a three-dimensional convolutional neural network

Dementia of Alzheimer's type (DAT) is associated with devastating and irreversible cognitive decline. Predicting which patients with mild cognitive impairment (MCI) will progress to DAT is an ongoing challenge in the field. We developed a deep learning model to predict conversion from MCI to DAT. Structural magnetic resonance imaging scans were used as input to a 3-dimensional convolutional neural network. The 3-dimensional convolutional neural network was trained using transfer learning; in the source task, normal control and DAT scans were used to pretrain the model. This pretrained model was then retrained on the target task of classifying which MCI patients converted to DAT. Our model resulted in 82.4% classification accuracy at the target task, outperforming current models in the field. Next, we visualized brain regions that significantly contribute to the prediction of MCI conversion using an occlusion map approach. Contributory regions included the pons, amygdala, and hippocampus. Finally, we showed that the model's prediction value is significantly correlated with rates of change in clinical assessment scores, indicating that the model is able to predict an individual patient's future cognitive decline. This information, in conjunction with the identified anatomical features, will aid in building a personalized therapeutic strategy for individuals with MCI.

A Novel Metabolic Connectome Method to Predict Progression to Mild Cognitive Impairment.

Objective Glucose-based positron emission tomography (PET) imaging has been widely used to predict the progression of mild cognitive impairment (MCI) into Alzheimer's disease (AD) clinically. However, existing discriminant methods are unsubtle to reveal pathophysiological changes. Therefore, we present a novel metabolic connectome-based predictive modeling to predict progression from MCI to AD accurately. Methods In this study, we acquired fluorodeoxyglucose PET images and clinical assessments from 420 MCI patients with 36 months follow-up. Individual metabolic network based on connectome analysis was constructed, and the metabolic connectivity in this network was extracted as predictive features. Three different classification strategies were implemented to interrogate the predictive performance. To verify the effectivity of selected features, specific brain regions associated with MCI conversion were identified based on these features and compared with prior knowledge. Results As a result, 4005 connectome features were obtained, and 153 in which were selected as efficient features. Our proposed feature extraction method had achieved 85.2% accuracy for MCI conversion prediction (sensitivity: 88.1%; specificity: 81.2%; and AUC: 0.933). The discriminative brain regions associated with MCI conversion were mainly located in the precentral gyrus, precuneus, lingual, and inferior frontal gyrus. Conclusion Overall, the results suggest that our proposed individual metabolic connectome method has great potential to predict whether MCI patients will progress to AD. The metabolic connectome may help to identify brain metabolic dysfunction and build a clinically applicable biomarker to predict the MCI progression.