Gray Areas: Is Preventing Frailty in Multiple Sclerosis a Realistic Goal?

Neurology moves fast, and the assumptions that shape how we practice do not always keep up. Gray Areas is a NeurologyLive series where leading clinicians and researchers challenge widely held beliefs across neurology, unpacking what the evidence actually shows, where it falls short, and where the field still has a lot of figuring out to do.

Tobia Zanotto, PhD, assistant professor in the Department of Occupational Therapy Education at the University of Kansas Medical Center and a researcher at the Landon Center on Aging, joined us to take on a question that is becoming increasingly relevant as people with MS are living longer: is preventing frailty in MS a realistic goal? Zanotto recently co-authored a position piece in Multiple Sclerosis Journal arguing that frailty prevention in MS is not only possible but a necessary clinical target,¹ and his group has conducted some of the earliest interventional research examining the effects of exercise and rehabilitation on frailty outcomes in this population.

In this episode, Zanotto unpacks what frailty actually means in the context of MS, how it differs from neurological disability, what the emerging evidence on lifestyle and rehabilitation interventions shows, and what the field needs to do to turn early findings into clinical practice.

Timeline

Segment 1: The Myth (0:56 - 5:10) — Dr. Zanotto addresses the misconception head-on, explaining that the debate around whether frailty can be prevented in MS largely stems from a definitional problem. He breaks down frailty as a biological syndrome shaped by age-related biology, lifestyle factors, and MS pathology, and explains why conflating frailty with neurological disability has muddied the conversation.

Segment 2: What the Evidence Shows (5:30 - 7:40) — A look at what the research has shown so far, including two studies from Dr. Zanotto's group demonstrating that motor training, cognitive motor training, and progressive resistance training can meaningfully reduce frailty levels in people with MS, with roughly one in five participants transitioning out of a higher frailty category.

Segment 3: Clinical Implications (8:18 - 8:50) — The downstream impact of frailty prevention in MS, including its potential to reduce falls, hospitalizations, and mortality, and what it could mean for patients as the field continues to shift toward a more holistic approach to MS management.

Segment 4: What We Still Don't Know (9:24 - End) — Dr. Zanotto outlines the research priorities the field needs to address, including larger interventional trials, better frailty measurement tools designed for the MS population, and a clearer understanding of whether frailty in MS is primarily driven by disease pathology or by lifestyle and comorbidity factors.

REFERENCE
1. Zanotto T, Sosnoff JJ. Preventing frailty in multiple sclerosis is a realistic goal: Yes. Mult Scler. 2026. doi:10.1177/13524585261466113