Aisen Paul S, Cummings Jeffrey, Jack Clifford R, Morris John C, Sperling Reisa, Frölich Lutz, Jones Roy W, Dowsett Sherie A, Matthews Brandy R, Raskin Joel, Scheltens Philip, Dubois Bruno
University of Southern California, San Diego, CA, USA.
Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA.
Alzheimers Res Ther. 2017 Aug 9;9(1):60. doi: 10.1186/s13195-017-0283-5.
Basic research advances in recent years have furthered our understanding of the natural history of Alzheimer's disease (AD). It is now recognized that pathophysiological changes begin many years prior to clinical manifestations of disease and the spectrum of AD spans from clinically asymptomatic to severely impaired. Defining AD purely by its clinical presentation is thus artificial and efforts have been made to recognize the disease based on both clinical and biomarker findings. Advances with biomarkers have also prompted a shift in how the disease is considered as a clinico-pathophysiological entity, with an increasing appreciation that AD should not only be viewed with discrete and defined clinical stages, but as a multifaceted process moving along a seamless continuum. Acknowledging this concept is critical to understanding the development process for disease-modifying therapies, and for initiating effective diagnostic and disease management options. In this article, we discuss the concept of a disease continuum from pathophysiological, biomarker, and clinical perspectives, and highlight the importance of considering AD as a continuum rather than discrete stages. While the pathophysiology of AD has still not been elucidated completely, there is ample evidence to support researchers and clinicians embracing the view of a disease continuum in their study, diagnosis, and management of the disease.
近年来的基础研究进展加深了我们对阿尔茨海默病（AD）自然史的理解。现在人们认识到，病理生理变化在疾病临床表现出现的许多年前就已开始，AD的范围涵盖从临床无症状到严重受损。因此，单纯根据临床表现来定义AD是人为的，人们已努力基于临床和生物标志物发现来识别该疾病。生物标志物的进展也促使人们对该疾病作为一种临床病理生理实体的认识发生转变，越来越多的人认识到，AD不应仅被视为具有离散且明确的临床阶段，而应被视为一个沿着无缝连续体发展的多方面过程。认识到这一概念对于理解疾病修饰疗法的开发过程以及启动有效的诊断和疾病管理方案至关重要。在本文中，我们从病理生理、生物标志物和临床角度讨论疾病连续体的概念，并强调将AD视为一个连续体而非离散阶段的重要性。虽然AD的病理生理学仍未完全阐明，但有充分证据支持研究人员和临床医生在对该疾病的研究、诊断和管理中接受疾病连续体的观点。
