Center for Multiple Sclerosis Research

nancy chiavarlottiThe Center for Multiple Sclerosis Research (CMSR) has been conducting research for over 20 years. Impairments in higher level cognitive processing, such as new learning and memory, are common in Multiple Sclerosis (MS) and negatively impact multiple aspects of everyday life, including occupational and social functioning. The researchers at the Center for Multiple Sclerosis Research conduct studies to increase our understanding of changes in cognition with MS, both from a functional, everyday life perspective and from a neuroanatomical perspective. Scientists are also studying ways to potentially minimize these deficits prior to their onset, or treat thereafter. Individual topic areas are discussed below.

Cognitive Rehabilitation in MS

Work from our center, as well as others, has shown that the memory problems that patients with MS experience are in learning new information, not retrieving previously learned information from memory storage. Patients have trouble remembering things such as tasks they need to do in a given day, an address or a list of items. They may have difficulty learning and remembering how to do a new task. These are all everyday applications of memory abilities.

It is this cognitive profile that makes persons with MS particularly appropriate for interventions targeting specific cognitive functions, such as new learning and memory or processing speed. If they are not showing a general cognitive decline, the cognitive decline is most often specific and subtle.

Our research at Kessler Foundation has shown that the modified “Story Memory Technique” (mSMT), which consists of training in context and imagery, improves learning and memory in MS. This treatment protocol also has demonstrated specific changes in the brain through changes in functional MRI from pre- to post-treatment.

Published evidence from our lab also shows that combination therapy is better than using one therapy in isolation. In fact, a newly funded study entails the application of three techniques that we have demonstrated can improve a person’s memory ability in a structured treatment protocol. It is an 8-session treatment that begins with education about memory abilities, what memory is – and is not – and how memory is impacted in MS. As treatment continues, two sessions are spent on each of three techniques that the patient is taught to apply to everyday memory situations.

Accumulated evidence demonstrating that each of these techniques improves learning and memory performance in MS supports the notion that the known deficit in new learning and memory can be specifically targeted and effectively treated through cognitive rehabilitation.

Management, Quality of Life & Outcomes Research in MS

Researchers in the Center for Multiple Sclerosis Research are interested in improving the care/treatment of individuals with MS, their overall quality of life, and various outcomes associated with MS (e.g., employment). In particular, employment, which has a significant influence on one’s quality of life, is known to be impacted greatly by MS. In fact, unemployment rates in MS range from 24% to 80%, with many becoming unemployed early in the disease. Given that many individuals with MS are in the prime of their lives and making important life decisions (e.g., family, career), it is imperative that we know what factors related to one’s MS contribute to these decisions. Such information can provide practitioners with invaluable information as to how these factors may influence the decision making process and can assist them in making informed decisions with their patients. With regard to management and treatment, researchers in the NNL are interested in medical adherence in MS. It is known that approximately 30% to 50% of patients will prematurely stop taking their disease modifying treatments, despite the known benefits of such treatments. We seek to understanding why individuals with MS may choose not to start or discontinue their medication prematurely. We are also interested in hurdles individuals may have in properly adhering to their medication regimen. By better understanding these issues, practitioners can improve their ability to assist patients in identifying the best plan for them.

Finally, improving the overall quality of life for individuals with MS is a main priority of the research conducted by CMSR investigators. Much of our research is focused on ameliorating fatigue, depression, sleep disturbances, personality changes, caregiver burden; improving self-efficacy, participation, and social activity represent major goals in much of the research we do. While there is still no cure for MS and individuals must contend with a variable and unpredictable disease, we hope that our interventions aimed at treating these modifiable secondary factors can ultimately improve the lives of individuals with MS and provide them with some mastery the disease.

Cognitive Reserve

Many persons with MS suffer cognitive decline, while others withstand advanced disease without cognitive impairment. That is, some persons with MS are protected against cognitive decline. Work within our laboratory has supported the “cognitive reserve” hypothesis in MS, demonstrating that mentally active lifestyles (e.g., reading, writing, hobbies) result in a brain that is better able to cope with disease without becoming inefficient or exhibiting memory problems. The cognitive reserve hypothesis was first developed in the aging/Alzheimer’s disease literature wherein researchers discovered that elders with higher educational attainment or more mentally active lifestyles are less likely to develop dementia. Here, we have shown that a history of mental activity (intellectual enrichment) allows persons with multiple sclerosis to cope with more disease-related brain changes (i.e., atrophy, lesions) without experiencing the cognitive slowing and memory problems characteristic of MS disease. We have also used functional magnetic resonance imaging (fMRI) to help identify patterns of brain activity that might underlie this protective benefit of mental activity. We are also beginning to investigate the cognitive reserve hypothesis in other populations, including traumatic brain injury. In sum, the cognitive reserve hypothesis helps explain why some persons are protected against disease-related cognitive decline, and our findings encourage engagement in mentally-active lifestyles for all persons. Although promising, cognitive reserve research across neurologic populations has been observational, whereby researchers investigate the impact of pre-existing patterns of mental activity on cognitive decline. The next step in this line of research is to investigate the causal relationship between intellectual enrichment (e.g., reading, playing games) and neurocognitive preservation through randomized controlled trials, such as one trial currently ongoing here at the Kessler Foundation. F

Functional Neuroimaging

We are currently conducting several studies that use functional neuroimaging as a ‘window into the mind’. Using this technique, we are able to visualize the brain areas that become active while subjects are performing particular tasks or are experiencing certain sensations. One example of this is work we are doing to investigate memory processes before and after a cognitive rehabilitation intervention (the story memory technique, see above). This has shown that this intervention actually changes the way that individuals with MS use their brains, such that they more effectively activate memory-related brain regions. Another example is work we are doing to discover the brain regions that are active when individuals with MS experience fatigue. Fatigue is a common problem in MS, and it has proven very difficult to study and to treat. Using functional neuroimaging, we have identified the brain regions that underlie the feeling of fatigue, and we are now beginning to use this information to formulate possible treatment interventions. Using a different kind of brain scan, ‘diffusion tensor imaging’ or DTI, we are able to track the fibers that connect different brain areas: the brain’s “white matter”. Because MS is a disease that primarily affects the brain’s white matter, this approach may be particularly revealing. One example of work we are pursuing with this type of scan involves fatigue. Using functional neuroimaging, we have identified a network of brain areas involved with fatigue (see above). We are now refining what we know about that network using DTI. We have found that different parts of this fatigue network appear to be involved in different aspects of fatigue. This is very exciting, since establishing a better understanding of fatigue will allow us to treat it more effectively.

Kessler Foundation continues to research these areas and develop new innovative ways to help alleviate the cognitive deficits related to Multiple Sclerosis.