Cascading network failure across the Alzheimer’s disease spectrum

作者：David T. Jones, David S. Knopman, Jeffrey L. Gunter, Jonathan Graff‐Radford, Prashanthi Vemuri, Bradley F. Boeve, Ronald C. Petersen, Michael W. Weiner, Clifford R. Jack · 发表于：Brain · 年份：2015 · DOI：10.1093/brain/awv338 · 被引用次数：574 · 研究领域：Functional Brain Connectivity Studies、Dementia and Cognitive Impairment Research、Alzheimer's disease research and treatments

Complex biological systems are organized across various spatiotemporal scales with particular scientific disciplines dedicated to the study of each scale (e.g. genetics, molecular biology and cognitive neuroscience). When considering disease pathophysiology, one must contemplate the scale at which the disease process is being observed and how these processes impact other levels of organization. Historically Alzheimer's disease has been viewed as a disease of abnormally aggregated proteins by pathologists and molecular biologists and a disease of clinical symptoms by neurologists and psychologists. Bridging the divide between these scales has been elusive, but the study of brain networks appears to be a pivotal inroad to accomplish this task. In this study, we were guided by an emerging systems-based conceptualization of Alzheimer's disease and investigated changes in brain networks across the disease spectrum. The default mode network has distinct subsystems with unique functional-anatomic connectivity, cognitive associations, and responses to Alzheimer's pathophysiology. These distinctions provide a window into the systems-level pathophysiology of Alzheimer's disease. Using clinical phenotyping, metadata, and multimodal neuroimaging data from the Alzheimer's Disease Neuroimaging Initiative, we characterized the pattern of default mode network subsystem connectivity changes across the entire disease spectrum (n = 128). The two main findings of this paper are (i) the posterior...