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Register a new userCognitive Biomarker Prioritization in Alzheimers Disease using Brain Morphometric Data
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Background:Cognitive assessments represent the most common clinical routine for the diagnosis of Alzheimers Disease (AD). Given a large number of cognitive assessment tools and time-limited office visits, it is important to determine a proper set of cognitive tests for different subjects. Most current studies create guidelines of cognitive test selection for a targeted population, but they are not customized for each individual subject. In this manuscript, we develop a machine learning paradigm enabling personalized cognitive assessments prioritization. Method: We adapt a newly developed learning-to-rank approach PLTR to implement our paradigm. This method learns the latent scoring function that pushes the most effective cognitive assessments onto the top of the prioritization list. We also extend PLTR to better separate the most effective cognitive assessments and the less effective ones. Results: Our empirical study on the ADNI data shows that the proposed paradigm outperforms the state-of-the-art baselines on identifying and prioritizing individual-specific cognitive biomarkers. We conduct experiments in cross validation and level-out validation settings. In the two settings, our paradigm significantly outperforms the best baselines with improvement as much as 22.1% and 19.7%, respectively, on prioritizing cognitive features. Conclusions: The proposed paradigm achieves superior performance on prioritizing cognitive biomarkers. The cognitive biomarkers prioritized on top have great potentials to facilitate personalized diagnosis, disease subtyping, and ultimately precision medicine in AD.
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Accurate diagnosis of Alzheimers Disease (AD) entails clinical evaluation of multiple cognition metrics and biomarkers. Metrics such as the Alzheimers Disease Assessment Scale - Cognitive test (ADAS-cog) comprise multiple subscores that quantify different aspects of a patients cognitive state such as learning, memory, and language production/comprehension. Although computer-aided diagnostic techniques for classification of a patients current disease state exist, they provide little insight into the relationship between changes in brain structure and different aspects of a patients cognitive state that occur over time in AD. We have developed a Convolutional Neural Network architecture that can concurrently predict the trajectories of the 13 subscores comprised by a subjects ADAS-cog examination results from a current minimally preprocessed structural MRI scan up to 36 months from image acquisition time without resorting to manual feature extraction. Mean performance metrics are within range of those of existing techniques that require manual feature selection and are limited to predicting aggregate scores.
Three major biomarkers: beta-amyloid (A), pathologic tau (T), and neurodegeneration (N), are recognized as valid proxies for neuropathologic changes of Alzheimers disease. While there are extensive studies on cerebrospinal fluids biomarkers (amyloid, tau), the spatial propagation pattern across brain is missing and their interactive mechanisms with neurodegeneration are still unclear. To this end, we aim to analyze the spatiotemporal associations between ATN biomarkers using large-scale neuroimaging data. We first investigate the temporal appearances of amyloid plaques, tau tangles, and neuronal loss by modeling the longitudinal transition trajectories. Second, we propose linear mixed-effects models to quantify the pathological interactions and propagation of ATN biomarkers at each brain region. Our analysis of the current data shows that there exists a temporal latency in the build-up of amyloid to the onset of tau pathology and neurodegeneration. The propagation pattern of amyloid can be characterized by its diffusion along the topological brain network. Our models provide sufficient evidence that the progression of pathological tau and neurodegeneration share a strong regional association, which is different from amyloid.
This work proposes a unified framework to leverage biological information in network propagation-based gene prioritization algorithms. Preliminary results on breast cancer data show significant improvements over state-of-the-art baselines, such as the prioritization of genes that are not identified as potential candidates by interactome-based algorithms, but that appear to be involved in/or potentially related to breast cancer, according to a functional analysis based on recent literature.
Current neuroimaging techniques provide paths to investigate the structure and function of the brain in vivo and have made great advances in understanding Alzheimers disease (AD). However, the group-level analyses prevalently used for investigation and understanding of the disease are not applicable for diagnosis of individuals. More recently, deep learning, which can efficiently analyze large-scale complex patterns in 3D brain images, has helped pave the way for computer-aided individual diagnosis by providing accurate and automated disease classification. Great progress has been made in classifying AD with deep learning models developed upon increasingly available structural MRI data. The lack of scale-matched functional neuroimaging data prevents such models from being further improved by observing functional changes in pathophysiology. Here we propose a potential solution by first learning a structural-to-functional transformation in brain MRI, and further synthesizing spatially matched functional images from large-scale structural scans. We evaluated our approach by building computational models to discriminate patients with AD from healthy normal subjects and demonstrated a performance boost after combining the structural and synthesized functional brain images into the same model. Furthermore, our regional analyses identified the temporal lobe to be the most predictive structural-region and the parieto-occipital lobe to be the most predictive functional-region of our model, which are both in concordance with previous group-level neuroimaging findings. Together, we demonstrate the potential of deep learning with large-scale structural and synthesized functional MRI to impact AD classification and to identify ADs neuroimaging signatures.
Purpose: This study investigates whether a machine-learning-based system can predict the rate of cognitive decline in mildly cognitively impaired patients by processing only the clinical and imaging data collected at the initial visit. Approach: We built a predictive model based on a supervised hybrid neural network utilizing a 3-Dimensional Convolutional Neural Network to perform volume analysis of Magnetic Resonance Imaging and integration of non-imaging clinical data at the fully connected layer of the architecture. The experiments are conducted on the Alzheimers Disease Neuroimaging Initiative dataset. Results: Experimental results confirm that there is a correlation between cognitive decline and the data obtained at the first visit. The system achieved an area under the receiver operator curve (AUC) of 0.70 for cognitive decline class prediction. Conclusion: To our knowledge, this is the first study that predicts slowly deteriorating/stable or rapidly deteriorating classes by processing routinely collected baseline clinical and demographic data (Baseline MRI, Baseline MMSE, Scalar Volumetric data, Age, Gender, Education, Ethnicity, and Race). The training data is built based on MMSE-rate values. Unlike the studies in the literature that focus on predicting Mild Cognitive Impairment-to-Alzheimer`s disease conversion and disease classification, we approach the problem as an early prediction of cognitive decline rate in MCI patients.
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