Cognitive impairment is a good predictor of physical disability progression in patients with multiple sclerosis (MS), new research suggests.

In an analysis of more than 1600 patients with secondary-progressive MS (SPMS), the likelihood of needing a wheelchair was almost doubled in those who had the worst scores on cognitive testing measures compared with their counterparts who had the best scores.

“These findings should change our world view of MS,” study investigator Gavin Giovannoni, PhD, professor of neurology, Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, United Kingdom, told attendees at the Congress of the European Academy of Neurology (EAN) 2022.

On the basis of the results, clinicians should consider testing cognitive processing speed in patients with MS to identify those who are at increased risk for disease progression, Giovannoni noted.

“I urge anybody who runs an MS service to think about putting in place mechanisms in their clinic” to measure cognition of patients over time, he said.

Expand Data

Cognitive impairment occurs very early in the course of MS and is part of the disease, although to a greater or lesser degree depending on the patient, Giovannoni noted. Such impairment has a significant impact on quality of life for patients dealing with this disease, he added.

EXPAND was a phase 3 study of siponimod. Results showed the now-approved oral selective sphingosine 1–phosphate receptor modulator significantly reduced the risk for disability progression in patients with SPMS.

Using the EXPAND clinical trial database, the current researchers assessed 1628 participants for an association between cognitive processing speed (CPS), as measured with the Symbol Digit Modality Test (SDMT), and physical disability progression, as measured with the Expanded Disability Status Scale (EDSS). A score of 7 or more on the EDSS indicates wheelchair dependence.

Giovanonni noted that CPS is considered an indirect measure of thalamic network efficiency and functional brain reserve.

Investigators looked at both the core study in which all patients continued on treatment or placebo for up to 37 months, and the core plus extension part in which patients received treatment for up to 5 years.

They separated SDMT scores into quartiles: from worst (n = 435) to two intermediate quartiles (n = 808) to the best quartile (n = 385).

Wheelchair Dependence

In addition, the researchers examined the predictive value by baseline SDMT, adjusting for treatment, age, gender, baseline EDSS score, baseline SCMT quartile, and treatment-by-baseline SCMT quartile interaction. On-study SDMT change (month 0-24) was also assessed after adjusting for treatment, age, gender, baseline EDS, baseline SCMT, and on-study change in SCMT quartile.

In the core study, those in the worst SDMT quartile at baseline were numerically more likely to reach deterioration to EDSS 7 or greater (wheelchair dependent) compared with patients in the best SDMT quartile (hazard ratio [HR], 1.31; 95% CI, .72-2.38; P = .371).

The short-term predictive value of baseline SDMT for reaching sustained EDSS of at least 7 was more obvious in the placebo arm than in the treatment arm.

Giovannoni said this is likely due to the treatment effect of siponimod preventing relatively more events in the worse quartile, and so reducing the risk for wheelchair dependency.

In the core plus extension part, there was an almost twofold increased risk for wheelchair dependence in the worse vs best SDMT groups (HR, 1.81; 95% CI, 1.17-2.78; P = .007).

Both baseline SDMT (HR, 1.81; P = .007) and on-study change in SDMT (HR, 1.73; P = .046) predicted wheelchair dependence in the long-term.

“More Important Than a Walking Stick”

Measuring cognitive change over time “may be a more important predictor than a walking stick in terms of quality of life and outcomes, and it affects clinical decision making,” said Giovannoni.

The findings are not novel, as post hoc analyses of other studies showed similar results. However, this new analysis adds more evidence to the importance of cognition in MS, Giovannoni noted.

“I have patients with EDSS of 0 or 1 who are profoundly disabled because of cognition. You shouldn’t just assume someone is not disabled because they don’t have physical disability,” he said.

However, Giovannoni noted that the study found an association and does not necessarily indicate a cause.

Antonia Lefter, MD, NeuroHope, Monza Oncologic Hospital, Bucharest, Romania, co-chaired the session highlighting the research.

Commenting for Medscape Medical News, she called this analysis from the “renowned” EXPAND study “valuable.”

In addition, it “underscores” the importance of assessing cognitive processing speed as it may predict long-term disability progression in patients with SPMS, Lefter said.

The study was funded by Novartis Pharma AG, Basel, Switzerland. Giovannoni, a steering committee member of the EXPAND trial, reported receiving consulting fees from AbbVie, Actelion, Atara Bio, Biogen, Celgene, Sanofi-Genzyme, Genentech, GlaxoSmithKline, Merck-Serono, Novartis, Roche, and Reva. He has also received compensation for research from Biogen, Roche, Merck-Serono, Novartis, Sanofi-Genzyme, and Takeda. Lefter has reported no relevant financial relationships.

Congress of the European Academy of Neurology (EAN) 2022. Abstract A-22-03304. Presented June 27, 2022.

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