Optimizing detection and prediction of changes in cognitive function in multiple sclerosis with novel ambulatory assessment methods

多发性硬化症(MS)是一种慢性中枢神经系统疾病，影响约100万人 在美国，这是导致年轻人非创伤性残疾的头号原因。认知功能障碍， 包括处理速度、视觉记忆、语言流畅性、工作记忆和执行力方面的缺陷 功能障碍是多发性硬化症最常见的问题之一，认知功能障碍对多发性硬化症的影响是可怕的 与健康相关的生活质量的许多方面。不幸的是，在开发预防性药物方面的进展， 多发性硬化症认知功能障碍的代偿性和恢复性干预受阻于我们的 了解它的自然历史、机制和对它最重要的影响-在日常生活中 患有多发性硬化症的人，我们对多发性硬化症认知功能的理解受到两个主要因素的限制： 测量限制和缺乏对潜在贡献者和后果的科学关注 认知能力下降。这项研究利用了技术辅助的动态评估的进步 为认知功能障碍的体验提供一个独特和多维的窗口的技术 多发性硬化患者的日常生活在本研究中，我们将使用多个互补的非卧床 更好地了解女士认知功能障碍的评估策略A定制智能手机应用程序将 用于管理一系列专门为系列设计的动态认知测试 生活环境管理以及生态瞬时评估(实时评估) 自我报告的症状和作为一个人的日常生活功能。这款智能手机应用程序将是 与加速计技术相结合，将提供客观、连续和不引人注目的测量 体力活动。动态评估将以“测量突发设计”进行。 包括超过两周的密集重复评估的爆发，纵向重复爆发，在 基线，以及一年和两年的随访。利用这些创新的评估手段和方法，我们将 测试主观和客观认知功能的动态测量是否对 认知功能的纵向变化(超过2年)，而不是传统的基于临床的“快照” 评估。我们还将研究短期(天)和长期(年)的时间关联 潜在的可修改因素-体力活动、睡眠、疲劳、疼痛、情绪和压力-以及 认知功能。最后，我们将研究认知功能与其他关键因素之间的联系 结果--社会和身体功能。这部作品的目的是更好地刻画 多发性硬化症的认知功能障碍，以确定在日常生活中影响认知功能的因素，并 突出可能受认知功能变化影响的功能领域。最终，这项工作将 指出评估认知功能的最佳方法，并将指导开发和测试 对MS患者的认知功能障碍进行预防性、补偿性和/或恢复性治疗。

Multiple sclerosis (MS) is a chronic disease of the central nervous system that affects approximately 1 million people in the US and is the #1 cause of non-traumatic disability in young adults. Cognitive dysfunction, including deficits in processing speed, visual memory, verbal fluency, working memory, and executive functioning, is one of the most common problems in MS. Cognitive dysfunction in MS exerts a dire impact on many aspects of health-related quality of life. Unfortunately, progress in developing preventative, compensatory and restorative interventions for cognitive dysfunction in MS is stymied by major gaps in our knowledge of its natural history, mechanisms, and impacts where it matters most – in the everyday lives of people with MS. Our understanding of cognitive function in MS is restricted by two major factors: measurement limitations and lack of scientific attention to potential contributors to and consequences of declines in cognition. This study leverages advances in technology-assisted ambulatory assessment techniques to provide a unique and multidimensional window onto the experience of cognitive dysfunction in the everyday lives of people with MS. In this study, we will use multiple complementary ambulatory assessment strategies to better understand cognitive dysfunction in MS. A customized smartphone app will be used to administer a battery of ambulatory cognitive tests that are designed specifically for serial administration in the lived environment as well as ecological momentary assessments (real-time assessment) of self-reported symptoms and functioning as a person goes about daily life. The smartphone app will be paired with accelerometer technology, which will provide objective, continuous, and unobtrusive measures of physical activity. Ambulatory assessments will be administered in a “measurement burst design,” incorporating bursts of intensive repeated assessment over two weeks, with bursts repeated longitudinally, at baseline, and 1- and 2- year follow-up. Using these innovative assessment measures and methods, we will test whether ambulatory measures of subjective and objective cognitive function are more sensitive to longitudinal changes (over 2 years) in cognitive functioning than conventional “snapshot” clinic-based assessments. We will also examine short- (days) and long-term (years) temporal associations between potentially modifiable factors - physical activity, sleep, fatigue, pain, mood, and stress – and changes in cognitive functioning. Finally, we will examine the association between cognitive functioning and other key outcomes - social and physical functioning. This work is designed to better characterize the natural history of cognitive dysfunction in MS, to identify factors that contribute to cognitive functioning in daily life, and to highlight functional domains that might be impacted by changes in cognitive function. Ultimately, this work will indicate optimal methods for assessing cognitive functioning and will guide development and testing of preventative, compensatory, and/or restorative treatments for cognitive dysfunction in MS.