Cognitive impairment (CI) in radiologically isolated syndrome (RIS) is associated with greater atrophy of cortical and subcortical gray matter and may be predictive of future multiple sclerosis (MS) risk, according to study results published in Multiple Sclerosis and Related Disorders.

This study included 17 patients with RIS between the ages of 18 and 55, recruited from existing MS databases at MS clinics in Spain. Study researchers recruited another 17 healthy sex-, age-, and education-matched healthy participants for a control group. Participants underwent neuropsychological assessments, including assessment of cognitive functioning using the Rao Brief Repeatable Battery and the Stroop test. Based on these assessments, patients with RIS were classified as either cognitively impaired (n=6) or cognitively preserved (n=11). Both patients and healthy controls also underwent magnetic resonance imaging (MRI) examinations, and had their normalized brain volumes measured.

In patients who were cognitively impaired, the main areas affected included verbal memory, sustained attention, information processing speed, and executive functions. Patients classified as cognitively impaired also had lower education levels and a trend towards lower employment.

There was a higher prevalence of severe depressive symptoms in patients with RIS who were cognitively impaired compared with those in the healthy control group. The cognitively impaired subgroup of patients with RIS also had a lower health-related quality of life in comparison.

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The quantitative MRI analysis found significant brain atrophy in patients who were cognitively impaired compared with the control group (P =.002) and cognitively preserved group (P =.038). Normalized gray matter volume (NGMV) was also lower in patients with CI compared with healthy controls. An analysis that included age and education level as covariates demonstrated a persistent significant association between CI and main atrophy measures (normalized brain volume: F=12.1[P <.001]; NGMV: F=7.8 [P <.01]; normalized cortical volume: F=9.2 [P <.001]).

A limitation of this study was the overall small sample size, which warrants future longitudinal studies with more robust sample sizes to verify the predictive value of CI for the conversion of RIS to MS.

Based on their findings, the study researchers concluded that their “data support that CI in RIS is associated with greater atrophy of both cortical and subcortical GM [gray matter], as occurs in MS, and could predict increased risk of MS.”

Disclosure:  This study was supported by Teva neuroscience. Please see the original reference for a full list of authors’ disclosures.


Domingo-Santos Á, Labiano-Fontcuberta A, Aladro-Benito Y, et al. Predicting conversion to multiple sclerosis by assessing cognitive impairment in radiologically isolated syndrome. Published online January 11, 2021. Mult Scler Relat Disord. doi:10.1016/j.msard.2021.102749