Three major biomarkers: beta-amyloid (A), pathologic tau (T), and neurodegeneration (N), are recognized as valid proxies for neuropathologic changes of Alzheimer's 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.
Columbia University（哥伦比亚大学）；Taub Institute（陶布研究所）；Sergievsky Center（谢尔吉耶夫斯基中心）；Mortimer B. Zuckerman Mind Brain Behavior Institute（莫蒂默·B·扎克曼心智大脑行为研究所）
Current neuroimaging techniques provide paths to investigate the structure and function of the brain in vivo and have made great advances in understanding Alzheimer's 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 cla…
A Review on Image- and Network-based Brain Data Analysis Techniques for Alzheimer's Disease Diagnosis Reveals a Gap in Developing Predictive Methods for Prognosis
University of Arizona（亚利桑那大学）；Mallinckrodt Institute of Radiology, Washington University（华盛顿大学马林克罗放射学研究所）；University of Utah（犹他大学）
The relationship between cognition and white matter hyperintensities (WMH) volumes often depends on the accuracy of the lesion segmentation algorithm used. As such, accurate detection and quantification of WMH is of great interest. Here, we use a deep learning-based WMH segmentation algorithm, StackGen-Net, to detect and quantify WMH on 3D FLAIR volumes from ADNI. We used a subset of subjects (n=20) and obtained manual WMH segmentations by an experienced neuro-radiologist to demonstrate the accuracy of our algorithm. On a larger cohort of subjects (n=290), we observed that larger WMH volumes c…
Early Detection of Alzheimer's Disease Using Explainable Machine Learning on Clinical Biomarkers: A Multi-Class Classification Study Using the Alzheimer's Disease Neuroimaging Initiative (ADNI) Dataset
Neuroimaging of large populations is valuable to identify factors that promote or resist brain disease, and to assist diagnosis, subtyping, and prognosis. Data-driven models such as convolutional neural networks (CNNs) have increasingly been applied to brain images to perform diagnostic and prognostic tasks by learning robust features. Vision transformers (ViT) - a new class of deep learning architectures - have emerged in recent years as an alternative to CNNs for several computer vision applications. Here we tested variants of the ViT architecture for a range of desired neuroimaging downstre…
Longitudinal Bayesian Learning of Continuous Disease Position across the Alzheimer's Disease Continuum
University of Texas Rio Grande Valley（德克萨斯大学里奥格兰德河谷分校）；University of Pittsburgh（匹兹堡大学）；Eli and Lilly Company（礼来公司）；Washington University in St. Louis（圣路易斯华盛顿大学）
An interpretable generative multimodal neuroimaging-genomics framework for decoding Alzheimer's disease
Department of Computer Science, University of Verona（威尼斯大学计算机科学系）；Department of Engineering for Innovation Medicine, University of Verona（威尼斯大学创新医学工程系）；Tri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology, Emory University（神经影像与数据科学转化研究三机构中心（TReNDS），佐治亚州立大学，佐治亚理工学院，埃默里大学）
Platform of Bioinformatics (PBI), University Lausanne Hospital (CHUV) and Faculty of Biology and Medicine (FBM), University of Lausanne (UNIL)（生物信息平台（PBI）、日内瓦大学医院（CHUV）和生物医学学院（FBM）、日内瓦大学（UNIL））；PBI, CHUV and FBM, UNIL（PBI、CHUV和FBM、UNIL）；Department of Biomedical Engineering, University of Basel（生物医学工程系、巴塞尔大学）；Roche Diagnostics International Ltd.（罗氏诊断国际有限公司）；F. Hoffmann - La Roche Ltd., Roche Information Solutions（F. Hoffmann-La Roche有限公司、罗氏信息解决方案）
Washington University School of Medicine（华盛顿大学医学院）
Objective Alzheimer disease (AD) is the most common cause of dementia, a syndrome characterized by cognitive impairment severe enough to interfere with activities of daily life. We aimed to conduct a systematic literature review (SLR) of studies that applied machine learning (ML) methods to clinical data derived from electronic health records in order to model risk for progression of AD dementia. Materials and Methods: We searched for articles published between January 1, 2010, and May 31, 2020, in PubMed, Scopus, ScienceDirect, IEEE Explore Digital Library, Association for Computing Machinery…
A Generalizable Feature Extractor for Alzheimer's-Related Brain MRI Tasks
McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University（麦吉尔大学蒙特利尔神经学研究所麦康奈尔脑成像中心）；Department of Biomedical Engineering, McGill University（麦吉尔大学生物医学工程系）
Neuroimaging data, e.g. obtained from magnetic resonance imaging (MRI), is comparably homogeneous due to (1) the uniform structure of the brain and (2) additional efforts to spatially normalize the data to a standard template using linear and non-linear transformations. Convolutional neural networks (CNNs), in contrast, have been specifically designed for highly heterogeneous data, such as natural images, by sliding convolutional filters over different positions in an image. Here, we suggest a new CNN architecture that combines the idea of hierarchical abstraction in neural networks with a pri…
Institute for Applied Computational Science, Harvard John A. Paulson School of Engineering and Applied Sciences（哈佛大学约翰·A·保尔森工程与应用科学学院应用计算科学研究所）
Alzheimer's Disease (AD) ravages the cognitive ability of more than 5 million Americans and creates an enormous strain on the health care system. This paper proposes a machine learning predictive model for AD development without medical imaging and with fewer clinical visits and tests, in hopes of earlier and cheaper diagnoses. That earlier diagnoses could be critical in the effectiveness of any drug or medical treatment to cure this disease. Our model is trained and validated using demographic, biomarker and cognitive test data from two prominent research studies: Alzheimer's Disease Neuroima…
