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Cognitive Health and Sphinogine-1-Phospate Receptor Modulators in Multiple Sclerosis - Episode 7

Overview of Brain Atrophy Data and Cognition Research in MS

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Flavia Nelson, MD, provides an overview of available brain atrophy data and cognition research in patients with multiple sclerosis.

Stephen Krieger, MD: Dr Nelson, you’ve done a lot of work in this area. Could you maybe tell us a little bit about your view of impactful research in atrophy, gray matter, atrophy and cognition, and perhaps some of your own work and how you’re doing this at the practice?

Flavia Nelson, MD: I think it’s complicated. Findings on MRI scans are not specific to cognition. We can see a patient that has brain atrophy, cortical atrophy, a lot of lesions in their brain, a lot of black holes. Everything plays a role. I want to bring up a couple of recent studies coming out of the group from Amsterdam who have done a significant amount of work on cognitive impairment in MRI findings. This is a group of 75 patients with MS, compared to 20 controls. What they did is, divided the patients into three groups depending on disability. And basically, what they found is that the more the disability, the more the findings on the MRI, obviously. Thalamic atrophy and corpus callosum atrophy were found in the not-so-disabled, but the more disabled they got, then they started finding more cortical atrophy and more brain atrophy. These are only 75 patients, but it’s still a good amount of subjects. There’s another study that came out of the University at Buffalo, The State University of New York, Dr Robert Zigadenus, MD, PhD, who has also done a lot of work in MRI findings, but this is a significant study because it’s 1900 patients. The reason I like it is because they follow patients over time for at least 5 years, and they showed that the rate of atrophy remained stable throughout the duration of the disease. It’s not like when they have more disability, the rate of atrophy is higher, but it is true that the more the disability, the more the atrophy.

Clearly, we can say or feel confident saying that the higher the disease load or the lesion burden, the higher the atrophy, the higher the cortical damage, and that correlates with disability. But interestingly, not everyone that has atrophy has cognitive impairment, right? You see people with a lot of atrophy, a lot of lesions, and they don’t have cognitive impairment and that is where the concept of James Sumowski’s, PhD, cognitive reserve plays a role. The smarter you are, the more knowledge you have, the more you study, the more languages you speak—those are going to prevent you from developing impairments. It’s very interesting, it can vary. We don’t really have time to talk about my research, however, I’ve done similar studies that have been cross-sectional, a little smaller, 40 patients, and yes, you see cortical atrophy, there are many measures that correlate with it, but again, you cannot just look at an MRI and say “OK, this patient has cognitive impairment.” Occasionally, you do, but you’re not always right so we need to come up with a way of creating a maybe a composite score that predicts or associates with cognitive impairment, but we don’t have it yet. Nevertheless, MRI and atrophy are definitely worth considering into the equation of whether the patient is at risk. One last thing, when I see a newly diagnosed patient with a lot of atrophy, I definitely bring it up that “There’s the potential that you will develop cognitive issues because the cognitive reserve exhausts over time at some point.” Thus, I do everything I can to use medications that perhaps play a role in decreasing atrophy, as well as recommend exercise and cognitive training, such as apps that help you with cognition, etc.

Stephen Krieger, MD: That’s great. You’ve taken the concept of assessing cognitive function and brain volume and atrophy and brought up implications for treatment.

Trancsript Edited for Clarity