Researchers Describe 5 Cognitive Phenotypes in Multiple Sclerosis

The findings suggest that this new categorization of cognitive deficits in multiple sclerosis may support clinicians in treatment choices and help tailor cognitive rehabilitation strategies, the authors said.

A recent study from Italy identified 5 cognitive phenotypes in multiple sclerosis (MS) in an effort to improve measures and definitions over traditional dichotomous classifications.

The authors said the findings suggest that this new categorization of cognitive deficits in MS may integrate the Expanded Disability Status Scale (EDSS) score in defining clinical disability, support clinicians in treatment choices, and help tailor cognitive rehabilitation strategies.

The 5 cognitive phenotypes are preserved cognition, mild–verbal memory/semantic fluency, mild–multidomain, severe–executive/attention, and severe–multidomain.

The cross-sectional study took place at 8 MS centers in Italy from January 1, 2010, to October 31, 2019; it

involved 1212 patients with MS and 196 healthy control individuals. Researchers used a date-driven approach known as applied latent profile analysis (LPA) to a set of neuropsychological data, and then used validated evaluations to characterize features obtained from MRIs.

Patients with MS had a mean age of 41.1 years (11.1) and 64.7% (784) were women. The healthy controls had a mean age of 40.4 years (8.6) and 66.3% (130) were women. All participants underwent neurological examinations and cognitive evaluations with the Rao Brief Repeatable Battery and Stroop Color and Word Test, with some undergoing MRI examinations. LPA was used on cognitive test z-scores to stratify cognitive phenotypes.

Preserved cognition was observed in 235 patients (19.4%), mild-verbal memory/semantic fluency was seen in 362 patients (29.9%), mild-multidomain involvement in 236 patients (19.5%), severe-executive attention in 167 patients (13.8%), and severe-multidomain in 212 patients (17.5%).

The authors wrote that “cognitive function was more properly represented as a continuum.”

Patients who were older and with more severe disease also had worse cognitive deficits. Patients with the severe–multidomain phenotype had extensive brain damage, with decreased volume in all the brain structures explored, except for nucleus pallidus, amygdala, and caudate nucleus.

The severe-multidomain phenotypes were seen in 36% of patients with secondary MS and 21% with primary progressive MS, as compared with 12% of patients with relapsing-remitting MS.

In addition, patients with the severe-multidomain phenotype had the worst levels of physical disability, with a median EDSS score of 3.0 (range, 0.0–8.0).

The study had a few limitations, such as the fact that the cross-sectional design did not permit a time-dependent association and evolution of phenotypes over time, and the clinical sample may not be entirely representative of a general MS population.


De Meo E, Portaccio E, Giorgio A, et al. Identifying the distinct cognitive phenotypes in Multiple Sclerosis. JAMA Neurol. Published online January 4, 2021. doi: 10.1001/jamaneurol.2020.4920