Cognitive impairment found to be common in untreated MS patients
Early motor symptoms, poor manual dexterity may predict decline: Study

Cognitive impairment is common in people with multiple sclerosis (MS) who have not previously received treatment, affecting about 1 in 4 patients, and rates are particularly higher in those with secondary progressive MS (SPMS), a new study found.
“The current study demonstrates that a significant portion of MS patients who are drug-naïve have CI [cognitive impairment],” the researchers wrote, noting their goal “to estimate the frequency and contributing factors for developing” problems with cognition.
Analyses done by the researchers, from Egypt, identified motor symptoms at disease onset and poor dexterity as key contributing factors of cognitive problems. While serum neurofilament light chain (sNfL) levels — an established marker of nerve cell damage — were elevated in people with cognitive impairment, sNfL was not independently contributing to cognitive issues, the data showed.
“Our findings emphasize the primary role of motor symptoms at onset and functional performance … as a predictor of CI in drug-naïve MS patients,” the researchers wrote. “sNFL remains a valuable biomarker for tracking disease activity and neurodegeneration but requires further investigation to establish its utility in predicting cognitive outcomes specifically.”
The study, “Motor symptoms at onset and manual dexterity predict cognitive impairment in drug-naïve individuals with multiple sclerosis,” was published in the Journal of Neuroimmunology.
Highest rates of cognitive impairment seen in SPMS patients
While MS is primarily marked by muscle weakness and walking difficulties, cognitive dysfunction is known to be a common symptom of the neurodegenerative disease, affecting as many as 90% of patients in some studies. Individuals with MS can experience a range of problems, including issues with memory and learning, as well as trouble with attention and information processing.
Indeed, such impairments can have a profound impact on the ability of people with MS to engage in daily activities, and may reduce their quality of life.
Because early detection of cognitive decline could allow for timely interventions, there is an urgent need to identify reliable markers that may predict the likelihood of cognitive impairment in a given patient. Still, the specific factors influencing cognitive performance in MS remain poorly understood.
Building on the hypothesis that neurodegeneration may play a major role in MS-related cognitive impairment, a team of researchers from institutions across Egypt now turned to sNfL as a potential biomarker of cognitive issues.
Elevated sNfL levels are consistently observed in MS patients compared with healthy individuals. However, its role as a biomarker specifically for cognitive status remains unclear, according to the team.
The study included 140 adults with MS who had never received treatment, known as drug-naïve. Most had relapsing-remitting disease (64.3%), and the most common presenting manifestations were motor symptoms (37.1%).
Each participant’s cognitive function was evaluated using the Brief International Cognitive Assessment for MS, or BICAMS. This is a quick and reliable tool consisting of three tests evaluating visuospatial memory, verbal learning and memory, and attention and information processing speed.
Based on their BICAMS scores, 38 patients (27.1%) were determined to have cognitive impairment, with verbal learning and memory being the most affected domain (40.7%).
People with SPMS had the highest rates of cognitive impairment (55.3%), while those with clinically isolated syndrome, or CIS — individuals who had experienced a first presentation of MS-like symptoms but had not progressed to clinically definite MS — were the least likely to exhibit cognitive impairment (11.8%).
Greater decline seen in patients with more disability, worse hand dexterity
Other significant differences also were seen between people with and without cognitive impairment. For example, those with cognitive impairment had significantly higher disability levels, worse hand and finger dexterity, and significantly higher sNfL levels. These patients also had fewer years of education.
When considering all study factors together, the data showed that only motor symptoms at disease onset and manual dexterity were significantly associated with cognitive impairment, according to the researchers.
“These findings underscore the importance of early assessment of motor function and physical disability to address cognitive outcomes in MS effectively,” the team wrote.
Meanwhile, in their analysis, sNfL failed to show an association with cognitive impairment, suggesting it is not a reliable marker.
“sNFL’s role appears to be more indicative of overall disease burden rather than a direct contributor to CI,” the team wrote.
These findings underscore the importance of early assessment of motor function and physical disability to address cognitive outcomes in MS effectively.
According to the researchers, the “acquired knowledge” from this study “may help manage cognitive decline as the disease progresses and aid in the early diagnosis of CI in MS.”
The team noted that “there are few previous studies of CI in drug naïve MS patients.” As such, these findings may provide insights to cognitive decline as seen in the natural disease course, the researchers noted.
“By focusing exclusively on drug-naïve patients, our study provides insights into the relationship between sNfL and CI without the confounding effects of disease-modifying therapies,” the team wrote.