Sarah Levy, PhD
Multiple Sclerosis (MS) patients often worry that the disease will diminish their ability to think and remember, along with their motor skills. Sarah Levy, PhD, Assistant Professor of Neurology at the Icahn School of Medicine at Mount Sinai, is working to address these concerns, studying the impact of MS on the brain and cognition and uncovering new possibilities for early interventions.
Dr. Levy arrived at Mount Sinai’s Corrine Goldsmith Dickinson Center for Multiple Sclerosis in 2020 with a PhD in clinical psychology and a passion for neuropsychology and neuroscience. She didn’t have extensive experience working with MS patients. But she knew that at the MS Center, she would be able to delve into an area that can be extremely concerning for patients when they receive an MS diagnosis: The potential effects of the condition on thinking and memory.
She was drawn to do a post-doctorate fellowship at Mount Sinai with James Sumowski, PhD, who researches modifiable risk and protective factors linked to cognitive decline.
“My prior research experience largely involved neuroimaging, which plays a central role in MS diagnosis and care,” says Dr. Levy, who is also Associate Director of the MS Cognitive Clinic. “Coming here allowed me to connect that work more directly to questions about cognition and brain–behavior relationships.”
As a result, Dr. Levy stayed on as faculty after her postdoc ended in 2022. Her current research focuses on several crucial areas, including how MS affects cognition; the possible impact of subtle neuroanatomical changes in the brain caused by the disease; and how MS affects cognition as patients age.
MS may affect patients’ thinking, but not in the ways researchers once thought
Besides affecting sensorimotor skills such as balance and coordination, clinicians and researchers have long known that MS can also affect a patient’s thinking and memory. But just as the latest disease-modifying therapies (DMTs) have helped keep severe motor symptoms at bay, these medications may also be changing the outlook for patients when it comes to their cognitive abilities.
Statistics show up to 70 percent of people with MS experience cognitive changes, particularly memory problems and slower information processing. But that outlook has changed with medications that work to quiet the disease’s signature lesions that can appear in the brain’s white matter, according to Dr. Levy.
“These lesions have been associated with cognitive dysfunction, but with our current DMTs, we can stop the formation of new lesions much better than in the past,” Dr. Levy says. “As a result, some cognitive issues, particularly processing speed, are less pronounced than before.”
For example, in a study recently published in the journal Brain, Dr. Sumowski, Dr. Levy and others at the MS Center found that patients with relapsing-remitting MS had normal processing speed, and slowed processing speed is now less of an issue for patients with progressive MS than previously.
That doesn’t mean MS has no effect on cognition. “Since our DMTs help reduce inflammation and protect against cognitive changes, cognition in MS patients now looks different and better,” says Dr. Levy.
She describes the cognitive issues as more subtle, and sometimes easier for patients to work around, but still frustrating. “We’re talking about things like word-finding difficulties, which are the number one cognitive complaint from our patients.”
The other concerns she hears from her MS patients: Losing one’s train of thought in a conversation; forgetting why they came into a room; and the dreaded “brain fog.”
“Many people with MS figure out how to navigate these challenges on their own. But we are working on how we can help with therapies such as cognitive remediation, which addresses these challenges by teaching practical strategies that patients can use every day,” she says.
MS, dementia and aging
Having trouble finding words is also something that happens with normal aging, which can make it difficult to determine whether a patient’s cognitive changes are due to MS or simply getting older. “It can be hard to tell the difference,” says Dr. Levy, who is studying what cognitive aging looks like in MS.
To better understand these distinctions, her current research is expanding to examine how age-related changes in MS compare with changes seen in other conditions, such as Alzheimer’s disease. She is recruiting participants for a study that uses PET scans and blood biomarkers to help make this distinction.
“Those with Alzheimer’s disease have what’s known as a buildup of beta-amyloid proteins in the brain. “In this study, we’ll look for these proteins in patients and combine that with comprehensive neuropsychological testing to see how patients with MS who don’t have these proteins differ from older adults without MS who do.” Early research suggests that people with MS may have lower rates of beta-amyloid in the brain.
“Anecdotally, we don’t often see people with MS with the kind of dense forgetting that occurs with Alzheimer’s disease,” she says. “I have patients with MS in their 70s and 80s who are fully oriented to things like date, time, and where they are—that’s very different from what we see in Alzheimer’s. And while it’s too early to know for sure, it’s an interesting question whether people with MS might have some protection from the disease.”
White matter vs. gray matter in the brain
Another way thinking about MS is changing: For decades, MS was thought of as an inflammatory condition that primarily affected the white matter in the brain. Now, researchers are learning that the gray matter may also be affected.
“In my research, I’m interested in the subtle neuroanatomical changes that may occur in the brain’s gray matter early on in MS, as well as the subtle cognitive changes that might bring,” says Dr. Levy.
Using neuroimaging in collaboration with Erin Beck, MD, PhD, Dr. Levy has found that early on, in some patients, there may be a very subtle loss in the thickness of the gray matter in the brain, known as cortical thickness.
These findings, she stresses, shouldn’t be cause for alarm. “I don’t want to worry patients,” Dr. Levy says. “We are talking about very subtle findings, micro changes, so small they are typically not even mentioned in a radiological report.”
While researchers are still learning about what these changes might mean, and how they might be related to possible cognitive and motor function, the research nevertheless holds promise for improving patients’ quality of life.
“These changes tend to occur very early on in the disease, which means we could have an opportunity to try immediate interventions, such as teaching patients strategies to compensate for possible cognitive changes, or even dietary changes, to help protect the brain,” she says.
Promise in protecting and helping the brain in people with MS
With advances in neuroimaging, clinicians are now able to detect MS at earlier, milder stages, and better understand what the disease looks like early on. That means that, with earlier intervention using DMTs alongside lifestyle modifications in diet, exercise, and sleep, clinicians can better protect patients’ cognitive health.
For MS patients experiencing cognitive symptoms—and even those who are not—Mount Sinai offers a comprehensive neuropsychological assessment clinic to help patients and their doctors get a sense of where they are.
“For every patient who comes through the MS Center, we can provide a baseline neuropsychological exam that looks at memory, attention, language, sensorimotor skills, and executive functioning,” says Dr. Levy. Then we can use this information for comparison over the years, if patients continue with regular testing.
“Just like we use MRIs to track lesions, we can track a patient’s cognitive function over time,” says Dr. Levy.
Mount Sinai neuropsychologists can also look for changes in mood, depression, anxiety, and sleep. “We can relay this information to our neurologists and point patients to interventions that might be helpful,” says Dr. Levy.
Mount Sinai also offers MS patients access to The C. Olsten Wellness Program, directed by Ilana Katz Sand, MD, and staffed with a nurse practitioner, physical therapist, a dietician, and social workers.
But patients are the true experts in what they are experiencing, whether changes in word-finding or walking.
“By listening carefully, we can keep adapting our clinical evaluations to be more sensitive to the issues patients are reporting,” says Dr. Levy. “It’s truly our patients who have allowed us to learn and understand what is happening in the brain, helping us advance the field in a meaningful way—and also shaping the way we care for them.”
If you are interested in participating in Dr. Levy’s forthcoming PET imaging study on cognitive aging and Alzheimer’s disease in MS, you can reach out to her directly at 347-503-5471 or email her at sarah.levy@mssm.edu.
By Paula Derrow, a multiple sclerosis patient and a professional writer.