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

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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.