Multi-Task Linear Programming Discriminant Analysis for the Identification of Progressive MCI Individuals

Accurately identifying mild cognitive impairment (MCI) individuals who will progress to Alzheimer''s disease (AD) is very important for making early interventions. Many classification methods focus on integrating multiple imaging modalities such as magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET). However, the main challenge for MCI classification using multiple imaging modalities is the existence of a lot of missing data in many subjects. For example, in the Alzheimer''s Disease Neuroimaging Initiative (ADNI) study, almost half of the subjects do not have PET images. In this paper, we propose a new and flexible binary classification method, namely Multi-task Linear Programming Discriminant (MLPD) analysis, for the incomplete multi-source feature learning. Specifically, we decompose the classification problem into different classification tasks, i.e., one for each combination of available data sources. To solve all different classification tasks jointly, our proposed MLPD method links them together by constraining them to achieve the similar estimated mean difference between the two classes (under classification) for those shared features. Compared with the state-of-the-art incomplete Multi-Source Feature (iMSF) learning method, instead of constraining different classification tasks to choose a common feature subset for those shared features, MLPD can flexibly and adaptively choose different feature subsets for different classification tasks. Furthermore, our proposed MLPD method can be efficiently implemented by linear programming. To validate our MLPD method, we perform experiments on the ADNI baseline dataset with the incomplete MRI and PET images from 167 progressive MCI (pMCI) subjects and 226 stable MCI (sMCI) subjects. We further compared our method with the iMSF method (using incomplete MRI and PET images) and also the single-task classification method (using only MRI or only subjects with both MRI and PET images). Experimental results show very promising performance of our proposed MLPD method.     

Automatic ROI Selection in Structural Brain MRI Using SOM 3D Projection

This paper presents a method for selecting Regions of Interest (ROI) in brain Magnetic Resonance Imaging (MRI) for diagnostic purposes, using statistical learning and vector quantization techniques. The proposed method models the distribution of GM and WM tissues grouping the voxels belonging to each tissue in ROIs associated to a specific neurological disorder. Tissue distribution of normal and abnormal images is modelled by a Self-Organizing map (SOM), generating a set of representative prototypes, and the receptive field (RF) of each SOM prototype defines a ROI. Moreover, the proposed method computes the relative importance of each ROI by means of its discriminative power. The devised method has been assessed using 818 images from the Alzheimer''s disease Neuroimaging Initiative (ADNI) which were previously segmented through Statistical Parametric Mapping (SPM). The proposed algorithm was used over these images to parcel ROIs associated to the Alzheimer''s Disease (AD). Additionally, this method can be used to extract a reduced set of discriminative features for classification, since it compresses discriminative information contained in the brain. Voxels marked by ROIs which were computed using the proposed method, yield classification results up to 90% of accuracy for controls (CN) and Alzheimer''s disease (AD) patients, and 84% of accuracy for Mild Cognitive Impairment (MCI) and AD patients.     

Multi-input deep learning approach for Cardiovascular Disease diagnosis using Myocardial Perfusion Imaging and clinical data

PurposeAccurate detection and treatment of Coronary Artery Disease is mainly based on invasive Coronary Angiography, which could be avoided provided that a robust, non-invasive detection methodology emerged. Despite the progress of computational systems, this remains a challenging issue. The present research investigates Machine Learning and Deep Learning methods in competing with the medical experts' diagnostic yield. Although the highly accurate detection of Coronary Artery Disease, even from the experts, is presently implausible, developing Artificial Intelligence models to compete with the human eye and expertise is the first step towards a state-of-the-art Computer-Aided Diagnostic system.MethodsA set of 566 patient samples is analysed. The dataset contains Polar Maps derived from scintigraphic Myocardial Perfusion Imaging studies, clinical data, and Coronary Angiography results. The latter is considered as reference standard. For the classification of the medical images, the InceptionV3 Convolutional Neural Network is employed, while, for the categorical and continuous features, Neural Networks and Random Forest classifier are proposed.ResultsThe research suggests that an optimal strategy competing with the medical expert's accuracy involves a hybrid multi-input network composed of InceptionV3 and a Random Forest. This method matches the expert's accuracy, which is 79.15% in the particular dataset.ConclusionImage classification using deep learning methods can cooperate with clinical data classification methods to enhance the robustness of the predicting model, aiming to compete with the medical expert's ability to identify Coronary Artery Disease subjects, from a large scale patient dataset.     

Multivariate protein signatures of pre-clinical Alzheimer's disease in the Alzheimer's disease neuroimaging initiative (ADNI) plasma proteome dataset

Background

Recent Alzheimer''s disease (AD) research has focused on finding biomarkers to identify disease at the pre-clinical stage of mild cognitive impairment (MCI), allowing treatment to be initiated before irreversible damage occurs. Many studies have examined brain imaging or cerebrospinal fluid but there is also growing interest in blood biomarkers. The Alzheimer''s Disease Neuroimaging Initiative (ADNI) has generated data on 190 plasma analytes in 566 individuals with MCI, AD or normal cognition. We conducted independent analyses of this dataset to identify plasma protein signatures predicting pre-clinical AD.

Methods and Findings

We focused on identifying signatures that discriminate cognitively normal controls (n = 54) from individuals with MCI who subsequently progress to AD (n = 163). Based on p value, apolipoprotein E (APOE) showed the strongest difference between these groups (p = 2.3×10⁻¹³). We applied a multivariate approach based on combinatorial optimization ((α,β)-k Feature Set Selection), which retains information about individual participants and maintains the context of interrelationships between different analytes, to identify the optimal set of analytes (signature) to discriminate these two groups. We identified 11-analyte signatures achieving values of sensitivity and specificity between 65% and 86% for both MCI and AD groups, depending on whether APOE was included and other factors. Classification accuracy was improved by considering “meta-features,” representing the difference in relative abundance of two analytes, with an 8-meta-feature signature consistently achieving sensitivity and specificity both over 85%. Generating signatures based on longitudinal rather than cross-sectional data further improved classification accuracy, returning sensitivities and specificities of approximately 90%.

Conclusions

Applying these novel analysis approaches to the powerful and well-characterized ADNI dataset has identified sets of plasma biomarkers for pre-clinical AD. While studies of independent test sets are required to validate the signatures, these analyses provide a starting point for developing a cost-effective and minimally invasive test capable of diagnosing AD in its pre-clinical stages.     

A blood-based screening tool for Alzheimer's disease that spans serum and plasma: findings from TARC and ADNI

Context

There is no rapid and cost effective tool that can be implemented as a front-line screening tool for Alzheimer''s disease (AD) at the population level.

Objective

To generate and cross-validate a blood-based screener for AD that yields acceptable accuracy across both serum and plasma.

Design, Setting, Participants

Analysis of serum biomarker proteins were conducted on 197 Alzheimer''s disease (AD) participants and 199 control participants from the Texas Alzheimer''s Research Consortium (TARC) with further analysis conducted on plasma proteins from 112 AD and 52 control participants from the Alzheimer''s Disease Neuroimaging Initiative (ADNI). The full algorithm was derived from a biomarker risk score, clinical lab (glucose, triglycerides, total cholesterol, homocysteine), and demographic (age, gender, education, APOE*E4 status) data.

Major Outcome Measures

Alzheimer''s disease.

Results

11 proteins met our criteria and were utilized for the biomarker risk score. The random forest (RF) biomarker risk score from the TARC serum samples (training set) yielded adequate accuracy in the ADNI plasma sample (training set) (AUC = 0.70, sensitivity (SN) = 0.54 and specificity (SP) = 0.78), which was below that obtained from ADNI cerebral spinal fluid (CSF) analyses (t-tau/Aβ ratio AUC = 0.92). However, the full algorithm yielded excellent accuracy (AUC = 0.88, SN = 0.75, and SP = 0.91). The likelihood ratio of having AD based on a positive test finding (LR+) = 7.03 (SE = 1.17; 95% CI = 4.49–14.47), the likelihood ratio of not having AD based on the algorithm (LR−) = 3.55 (SE = 1.15; 2.22–5.71), and the odds ratio of AD were calculated in the ADNI cohort (OR) = 28.70 (1.55; 95% CI = 11.86–69.47).

Conclusions

It is possible to create a blood-based screening algorithm that works across both serum and plasma that provides a comparable screening accuracy to that obtained from CSF analyses.     

A Hybrid CNN-SVM Threshold Segmentation Approach for Tumor Detection and Classification of MRI Brain Images

ObjectiveIn this research paper, the brain MRI images are going to classify by considering the excellence of CNN on a public dataset to classify Benign and Malignant tumors.Materials and MethodsDeep learning (DL) methods due to good performance in the last few years have become more popular for Image classification. Convolution Neural Network (CNN), with several methods, can extract features without using handcrafted models, and eventually, show better accuracy of classification. The proposed hybrid model combined CNN and support vector machine (SVM) in terms of classification and with threshold-based segmentation in terms of detection.ResultThe findings of previous studies are based on different models with their accuracy as Rough Extreme Learning Machine (RELM)-94.233%, Deep CNN (DCNN)-95%, Deep Neural Network (DNN) and Discrete Wavelet Autoencoder (DWA)-96%, k-nearest neighbors (kNN)-96.6%, CNN-97.5%. The overall accuracy of the hybrid CNN-SVM is obtained as 98.4959%.ConclusionIn today's world, brain cancer is one of the most dangerous diseases with the highest death rate, detection and classification of brain tumors due to abnormal growth of cells, shapes, orientation, and the location is a challengeable task in medical imaging. Magnetic resonance imaging (MRI) is a typical method of medical imaging for brain tumor analysis. Conventional machine learning (ML) techniques categorize brain cancer based on some handicraft property with the radiologist specialist choice. That can lead to failure in the execution and also decrease the effectiveness of an Algorithm. With a brief look came to know that the proposed hybrid model provides more effective and improvement techniques for classification.     

Arrhythmic Heartbeat Classification Using 2D Convolutional Neural Networks

BackgroundElectrocardiogram (ECG) is a method of recording the electrical activity of the heart and it provides a diagnostic means for heart-related diseases. Arrhythmia is any irregularity of the heartbeat that causes an abnormality in the heart rhythm. Early detection of arrhythmia has great importance to prevent many diseases. Manual analysis of ECG recordings is not practical for quickly identifying arrhythmias that may cause sudden deaths. Hence, many studies have been presented to develop computer-aided-diagnosis (CAD) systems to automatically identify arrhythmias.MethodsThis paper proposes a novel deep learning approach to identify arrhythmias in ECG signals. The proposed approach identifies arrhythmia classes using Convolutional Neural Network (CNN) trained by two-dimensional (2D) ECG beat images. Firstly, ECG signals, which consist of 5 different arrhythmias, are segmented into heartbeats which are transformed into 2D grayscale images. Afterward, the images are used as input for training a new CNN architecture to classify heartbeats.ResultsThe experimental results show that the classification performance of the proposed approach reaches an overall accuracy of 99.7%, sensitivity of 99.7%, and specificity of 99.22% in the classification of five different ECG arrhythmias. Further, the proposed CNN architecture is compared to other popular CNN architectures such as LeNet and ResNet-50 to evaluate the performance of the study.ConclusionsTest results demonstrate that the deep network trained by ECG images provides outstanding classification performance of arrhythmic ECG signals and outperforms similar network architectures. Moreover, the proposed method has lower computational costs compared to existing methods and is more suitable for mobile device-based diagnosis systems as it does not involve any complex preprocessing process. Hence, the proposed approach provides a simple and robust automatic cardiac arrhythmia detection scheme for the classification of ECG arrhythmias.     

Identifying brain hierarchical structures associated with Alzheimer's disease using a regularized regression method with tree predictors

Brain segmentation at different levels is generally represented as hierarchical trees. Brain regional atrophy at specific levels was found to be marginally associated with Alzheimer's disease outcomes. In this study, we propose an ℓ₁-type regularization for predictors that follow a hierarchical tree structure. Considering a tree as a directed acyclic graph, we interpret the model parameters from a path analysis perspective. Under this concept, the proposed penalty regulates the total effect of each predictor on the outcome. With regularity conditions, it is shown that under the proposed regularization, the estimator of the model coefficient is consistent in ℓ₂-norm and the model selection is also consistent. When applied to a brain sMRI dataset acquired from the Alzheimer's Disease Neuroimaging Initiative (ADNI), the proposed approach identifies brain regions where atrophy in these regions demonstrates the declination in memory. With regularization on the total effects, the findings suggest that the impact of atrophy on memory deficits is localized from small brain regions, but at various levels of brain segmentation. Data used in preparation of this paper were obtained from the ADNI database.     

针灸联合多奈哌齐和美金刚对重度老年痴呆患者行为能力和认知功能的影响

目的:研究针灸联合多奈哌齐和美金刚对重度老年痴呆患者行为能力和认知功能的影响。方法:选择2015年1月～2018年12月在我院精神科进行诊治的50例重度老年痴呆患者,采用随机数字表法将其平均分为两组,每组25例。对照组患者口服多奈哌齐以及美金刚治疗,初始给药剂量均为每天口服5 mg,逐渐将给药剂量升高至每天口服20 mg,每次1片,每天2次。观察组患者采取针灸联合多奈哌齐和美金刚治疗,每天针灸治疗1次,每治疗6 d后休息1 d。两组患者均连续治疗4周。记录和比较两组患者治疗前后的日常生活能力与认知功能的变化情况。结果:观察组患者治疗4w后的治疗有效率为92.00%(23/25),明显高于对照组[68.00%(17/25)](P0.05);两组治疗4w后的MMSE和BI评分均显著高于治疗前(P0.05),且观察组以上指标均显著高于对照组(P0.05)。结论:针灸联合多奈哌齐和美金刚对重度老年痴呆患者的治疗效果明显优于单纯使用多奈哌齐和美金刚治疗,其可更有效改善患者的行为能力和认知功能。     

Classification of Early Stages of Esophageal Cancer Using Transfer Learning

ObjectivesEsophageal Cancer is the sixth most common cancer with a high fatality rate. Early prognosis of esophageal abnormalities can improve the survival rate of the patients. The sequence of the progress of the esophageal cancer is from esophagitis to non-dysplasia Barrett's esophagus to dysplasia Barrett's esophagus to esophageal adenocarcinoma (EAC). Many studies revealed a 5-fold increase in EAC patients diagnosed with esophagitis, and those diagnosed with Barrett's esophagus have a greater risk of EAC.Material and methodsConvolutional Neural Network (CNN) with efficient feature extractors enable better prognosis of the pre cancerous stage, Barrett's esophagus and esophagitis. The transfer learning techniques with CNN can extract more relevant features for the automated classification of Barrett's esophagus and esophagitis. This paper presents a study on the classification of the esophagitis and Barrett's esophagus (BE) using Deep Convolution Neural Networks (DCNN).ResultsIn the first experiment, the DCNN models perform as a feature extractor, and standard classifiers do the classification. The performance analysis shows that the CNN model ResNet50 with Support Vector Machine (SVM) has an accuracy of 93.5%, recall 93.5%, precision 93.4%, f score 93.5%, AUC 89.8%. In the second experiment, the DCNN classification models perform the classification with Transfer Learning and fine-tuning. The ResNet50 model has improved accuracy of 94.46%, precision 94.46%, f score 94.46%, AUC 96.20%.ConclusionThe ResNet50 model with transfer learning and fine-tuning gives a better performance than the ResNet50 model with SVM classifier. Our experiments show that the DCNN is effective for diagnosing EAC, both as feature extractors and classification models with transfer learning and fine-tuning.     

Automated classification of urinary stones based on microcomputed tomography images using convolutional neural network

PurposeThe classification of urinary stones is important prior to treatment because the treatments depend on three types of urinary stones, i.e., calcium, uric acid, and mixture stones. We have developed an automatic approach for the classification of urinary stones into the three types based on microcomputed tomography (micro-CT) images using a convolutional neural network (CNN).Materials and methodsThirty urinary stones from different patients were scanned in vitro using micro-CT (pixel size: 14.96 μm; slice thickness: 15 μm); a total of 2,430 images (micro-CT slices) were produced. The slices (227 × 227 pixels) were classified into the three categories based on their energy dispersive X-ray (EDX) spectra obtained via scanning electron microscopy (SEM). The images of urinary stones from each category were divided into three parts; 66%, 17%, and 17% of the dataset were assigned to the training, validation, and test datasets, respectively. The CNN model with 15 layers was assessed based on validation accuracy for the optimization of hyperparameters such as batch size, learning rate, and number of epochs with different optimizers. Then, the model with the optimized hyperparameters was evaluated for the test dataset to obtain classification accuracy and error.ResultsThe validation accuracy of the developed approach with CNN with optimized hyperparameters was 0.9852. The trained CNN model achieved a test accuracy of 0.9959 with a classification error of 1.2%.ConclusionsThe proposed automated CNN-based approach could successfully classify urinary stones into three types, namely calcium, uric acid, and mixture stones, using micro-CT images.     

Intra-individual variability in Alzheimer's disease and cognitive aging: definitions, context, and effect sizes

Background/Aims

To explore different definitions of intra-individual variability (IIV) to summarize performance on commonly utilized cognitive tests (Mini Mental State Exam; Clock Drawing Test); compare them and their potential to differentiate clinically-defined populations; and to examine their utility in predicting clinical change in individuals from the Alzheimer''s Disease Neuroimaging Initiative (ADNI).

Methods

Sample statistics were computed from ADNI cohorts with no cognitive diagnosis, a diagnosis of mild cognitive impairment (MCI), and a diagnosis of possible or probable Alzheimer''s disease (AD). Nine different definitions of IIV were computed for each sample, and standardized effect sizes (Cohen''s d) were computed for each of these definitions in 500 simulated replicates using scores on the Mini Mental State Exam and Clock Drawing Test. IIV was computed based on test items separately (‘within test’ IIV) and the two tests together (‘across test’ IIV). The best performing definition was then used to compute IIV for a third test, the Alzheimer''s Disease Assessment Scale-Cognitive, and the simulations and effect sizes were again computed. All effect size estimates based on simulated data were compared to those computed based on the total scores in the observed data. Association between total score and IIV summaries of the tests and the Clinician''s Dementia Rating were estimated to test the utility of IIV in predicting clinically meaningful changes in the cohorts over 12- and 24-month intervals.

Results

ES estimates differed substantially depending on the definition of IIV and the test(s) on which IIV was based. IIV (coefficient of variation) summaries of MMSE and Clock-Drawing performed similarly to their total scores, the ADAS total performed better than its IIV summary.

Conclusion

IIV can be computed within (items) or across (totals) items on commonly-utilized cognitive tests, and may provide a useful additional summary measure of neuropsychological test performance.     

FLCRM: Functional linear cox regression model

Summary

We consider a functional linear Cox regression model for characterizing the association between time‐to‐event data and a set of functional and scalar predictors. The functional linear Cox regression model incorporates a functional principal component analysis for modeling the functional predictors and a high‐dimensional Cox regression model to characterize the joint effects of both functional and scalar predictors on the time‐to‐event data. We develop an algorithm to calculate the maximum approximate partial likelihood estimates of unknown finite and infinite dimensional parameters. We also systematically investigate the rate of convergence of the maximum approximate partial likelihood estimates and a score test statistic for testing the nullity of the slope function associated with the functional predictors. We demonstrate our estimation and testing procedures by using simulations and the analysis of the Alzheimer's Disease Neuroimaging Initiative (ADNI) data. Our real data analyses show that high‐dimensional hippocampus surface data may be an important marker for predicting time to conversion to Alzheimer's disease. Data used in the preparation of this article were obtained from the ADNI database ( adni.loni.usc.edu ).     

Neural network on interval-censored data with application to the prediction of Alzheimer's disease

Alzheimer's disease (AD) is a progressive and polygenic disorder that affects millions of individuals each year. Given that there have been few effective treatments yet for AD, it is highly desirable to develop an accurate model to predict the full disease progression profile based on an individual's genetic characteristics for early prevention and clinical management. This work uses data composed of all four phases of the Alzheimer's Disease Neuroimaging Initiative (ADNI) study, including 1740 individuals with 8 million genetic variants. We tackle several challenges in this data, characterized by large-scale genetic data, interval-censored outcome due to intermittent assessments, and left truncation in one study phase (ADNIGO). Specifically, we first develop a semiparametric transformation model on interval-censored and left-truncated data and estimate parameters through a sieve approach. Then we propose a computationally efficient generalized score test to identify variants associated with AD progression. Next, we implement a novel neural network on interval-censored data (NN-IC) to construct a prediction model using top variants identified from the genome-wide test. Comprehensive simulation studies show that the NN-IC outperforms several existing methods in terms of prediction accuracy. Finally, we apply the NN-IC to the full ADNI data and successfully identify subgroups with differential progression risk profiles. Data used in the preparation of this article were obtained from the ADNI database.     

Analysis of secondary phenotypes in multigroup association studies

Although case-control association studies have been widely used, they are insufficient for many complex diseases, such as Alzheimer's disease and breast cancer, since these diseases may have multiple subtypes with distinct morphologies and clinical implications. Many multigroup studies, such as the Alzheimer's Disease Neuroimaging Initiative (ADNI), have been undertaken by recruiting subjects based on their multiclass primary disease status, while extensive secondary outcomes have been collected. The aim of this paper is to develop a general regression framework for the analysis of secondary phenotypes collected in multigroup association studies. Our regression framework is built on a conditional model for the secondary outcome given the multigroup status and covariates and its relationship with the population regression of interest of the secondary outcome given the covariates. Then, we develop generalized estimation equations to estimate the parameters of interest. We use both simulations and a large-scale imaging genetic data analysis from the ADNI to evaluate the effect of the multigroup sampling scheme on standard genome-wide association analyses based on linear regression methods, while comparing it with our statistical methods that appropriately adjust for the multigroup sampling scheme. Data used in preparation of this article were obtained from the ADNI database.     

Implementation of Neural Networks to Frontal Electroencephalography for the Identification of the Transition Responsiveness/Unresponsiveness During Induction of General Anesthesia

ObjectiveGeneral anesthesia is a reversible drug-induced state of altered arousal characterized by loss of responsiveness (LOR) due to brainstem inactivation. Precise identification of the LOR during the induction of general anesthesia is extremely important to provide personalized information on anesthetic requirements and could help maintain an adequate level of anesthesia throughout surgery, ensuring safe and effective care and balancing the avoidance of intraoperative awareness and overdose. So, main objective of this paper was to investigate whether a Convolutional Neural Network (CNN) applied to bilateral frontal electroencephalography (EEG) dataset recorded from patients during opioid-propofol anesthetic procedures identified the exact moment of LOR.Material and methodsA clinical protocol was designed to allow for the characterization of different clinical endpoints throughout the transition to unresponsiveness. Fifty (50) patients were enrolled in the study and data from all was included in the final dataset analysis. While under a constant estimated effect-site concentration of 2.5 ng/mL of remifentanil, an 1% propofol infusion was started at 3.3 mL//h until LOR. The level of responsiveness was assessed by an anesthesiologist every six seconds using a modified version of the Richmond Agitation-Sedation Scale (aRASS). The frontal EEG was acquired using a bilateral bispectral (BIS VISTA™ v2.0, Medtronic, Ireland) sensor. EEG data was then split into 5-second epochs, and for each epoch, the anesthesiologist's classification was used to label it as responsiveness (no-LOR) or unresponsiveness (LOR). All 5-second epochs were then used as inputs for the CNN model to classify the untrained segment as no-LOR or LOR.ResultsThe CNN model was able to identify the transition from no-LOR to LOR successfully, achieving 97.90±0.07% accuracy on the cross-validation set.ConclusionThe obtained results showed that the proposed CNN model was quite efficient in the responsiveness/unresponsiveness classification. We consider our approach constitutes an additional technique to the current methods used in the daily clinical setting where LOR is identified by the loss of response to verbal commands or mechanical stimulus. We therefore hypothesized that automated EEG analysis could be a useful tool to detect the moment of LOR, especially using machine learning approaches.     

A Computationally Efficient Correlational Neural Network for Automated Prediction of Chronic Kidney Disease

ObjectivesIn this paper, we propose a computationally efficient Correlational Neural Network (CorrNN) learning model and an automated diagnosis system for detecting Chronic Kidney Disease (CKD). A Support Vector Machine (SVM) classifier is integrated with the CorrNN model for improving the prediction accuracy.Material and methodsThe proposed hybrid model is trained and tested with a novel sensing module. We have monitored the concentration of urea in the saliva sample to detect the disease. Experiments are carried out to test the model with real-time samples and to compare its performance with conventional Convolutional Neural Network (CNN) and other traditional data classification methods.ResultsThe proposed method outperforms the conventional methods in terms of computational speed and prediction accuracy. The CorrNN-SVM combined network achieved a prediction accuracy of 98.67%. The experimental evaluations show a reduction in overall computation time of about 9.85% compared to the conventional CNN algorithm.ConclusionThe use of the SVM classifier has improved the capability of the network to make predictions more accurately. The proposed framework substantially advances the current methodology, and it provides more precise results compared to other data classification methods.     

Genome-Wide Association Study of CSF Levels of 59 Alzheimer's Disease Candidate Proteins: Significant Associations with Proteins Involved in Amyloid Processing and Inflammation

Cerebrospinal fluid (CSF) 42 amino acid species of amyloid beta (Aβ42) and tau levels are strongly correlated with the presence of Alzheimer''s disease (AD) neuropathology including amyloid plaques and neurodegeneration and have been successfully used as endophenotypes for genetic studies of AD. Additional CSF analytes may also serve as useful endophenotypes that capture other aspects of AD pathophysiology. Here we have conducted a genome-wide association study of CSF levels of 59 AD-related analytes. All analytes were measured using the Rules Based Medicine Human DiscoveryMAP Panel, which includes analytes relevant to several disease-related processes. Data from two independently collected and measured datasets, the Knight Alzheimer''s Disease Research Center (ADRC) and Alzheimer''s Disease Neuroimaging Initiative (ADNI), were analyzed separately, and combined results were obtained using meta-analysis. We identified genetic associations with CSF levels of 5 proteins (Angiotensin-converting enzyme (ACE), Chemokine (C-C motif) ligand 2 (CCL2), Chemokine (C-C motif) ligand 4 (CCL4), Interleukin 6 receptor (IL6R) and Matrix metalloproteinase-3 (MMP3)) with study-wide significant p-values (p<1.46×10⁻¹⁰) and significant, consistent evidence for association in both the Knight ADRC and the ADNI samples. These proteins are involved in amyloid processing and pro-inflammatory signaling. SNPs associated with ACE, IL6R and MMP3 protein levels are located within the coding regions of the corresponding structural gene. The SNPs associated with CSF levels of CCL4 and CCL2 are located in known chemokine binding proteins. The genetic associations reported here are novel and suggest mechanisms for genetic control of CSF and plasma levels of these disease-related proteins. Significant SNPs in ACE and MMP3 also showed association with AD risk. Our findings suggest that these proteins/pathways may be valuable therapeutic targets for AD. Robust associations in cognitively normal individuals suggest that these SNPs also influence regulation of these proteins more generally and may therefore be relevant to other diseases.     

The risk prediction of Alzheimer’s disease based on the deep learning model of brain 18F-FDG positron emission tomography

In order to predict the risks of Alzheimer’s Disease (AD) based on the deep learning model of brain 18F-FDG positron emission tomography (PET), a total of 350 mild cognitive impairment (MCI) participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database were selected as the research objects; in addition, the Convolutional Architecture for Fast Feature Embedding (CAFFE) was selected as the framework of the deep learning platform; the FDG PET image features of each participant were extracted by a deep convolution network model to construct the prediction and classification models; therefore, the MCI stage features were classified and the transformation was predicted. The results showed that in terms of the MCI transformation prediction, the sensitivity and specificity of conv3 classification were respectively 91.02% and 77.63%; in terms of the Late Mild Cognitive Impairment (LMCI) and Early Mild Cognitive Impairment (EMCI) classification, the accuracy of conv5 classification was 72.19%, and the sensitivity and specificity of conv5 were all 73% approximately. Thus, it was seen that the model constructed in the research could be used to solve the problems of MCI transformation prediction, which also had certain effects on the classifications of EMCI and LMCI. The risk prediction of AD based on the deep learning model of brain 18F-FDG PET discussed in the research matched the expected results. It provided a relatively accurate reference model for the prediction of AD. Despite the deficiencies of the research process, the research results have provided certain references and guidance for the future exploration of accurate AD prediction model; therefore, the research is of great significance.     

Hierarchical Interactions Model for Predicting Mild Cognitive Impairment (MCI) to Alzheimer's Disease (AD) Conversion

Identifying patients with Mild Cognitive Impairment (MCI) who are likely to convert to dementia has recently attracted increasing attention in Alzheimer''s disease (AD) research. An accurate prediction of conversion from MCI to AD can aid clinicians to initiate treatments at early stage and monitor their effectiveness. However, existing prediction systems based on the original biosignatures are not satisfactory. In this paper, we propose to fit the prediction models using pairwise biosignature interactions, thus capturing higher-order relationship among biosignatures. Specifically, we employ hierarchical constraints and sparsity regularization to prune the high-dimensional input features. Based on the significant biosignatures and underlying interactions identified, we build classifiers to predict the conversion probability based on the selected features. We further analyze the underlying interaction effects of different biosignatures based on the so-called stable expectation scores. We have used 293 MCI subjects from Alzheimer''s Disease Neuroimaging Initiative (ADNI) database that have MRI measurements at the baseline to evaluate the effectiveness of the proposed method. Our proposed method achieves better classification performance than state-of-the-art methods. Moreover, we discover several significant interactions predictive of MCI-to-AD conversion. These results shed light on improving the prediction performance using interaction features.