New classification of cognitive phenotypes for sufferers with MS

A new classification of cognitive deficits in patients with multiple sclerosis (MS), according to the study results published in JAMA Neurology, can be helpful in defining clinical disabilities, assisting clinicians in treatment selection and tailoring cognitive rehabilitation strategies.

While cognitive dysfunction is common in MS patients, the heterogeneity of cognitive deficits in these patients prevents a clear assessment of neuroanatomical substrates and personalized rehabilitation strategies. The aim of the current study was to define cognitive phenotypes in a clinical cohort of MS patients and to characterize their clinical and MRI features.

The cross-sectional study included 1212 patients (mean age 41.1 years; 64.7% women) with MS and 196 healthy control persons (mean age 40.4 years; 66.3% women) from 8 Italians from January 1, 2010 to October 31, 2010 Centers. 2019. No participants were taking psychotropic drugs and none had a history of other neurological or medical disorders, learning disorders, severe head trauma, or alcohol or drug abuse.

All study participants performed neuropsychological examinations with the Rao Brief Repeatable Battery and the Stroop Color and Word Test. At the time of the neuropsychological examination, 172 patients with MS and 50 participants in the healthy control group had an MRI scan of the brain.

The study researchers used latent profile analysis (LPA) for cognitive test z-scores to identify cognitive phenotypes, and they used statistical analysis to compare demographic and clinical parameters and radiological characteristics of each phenotype.

Using LPA, they identified these 5 cognitive phenotypes compared to healthy control group participants:

  • Preserved cognition: 235 patients (19.4%) showed no significant difference
  • Mild verbal memory / semantic fluence: 362 patients (29.9%) in whom the selective memory test and the generation of word lists decreased only slightly
  • Mild multi-domain: 236 patients (19.5%) who were mildly stimulated on the Selective Memory Test, the Symbol Digit Modality Test, the Stroop Color and Word Test, and the Auditory Serial Addition Test
  • Heavy Executive / Attention: 167 patients (13.8%) whose performance in the Stroop Color and Word Test and in the Paced Auditory Serial Addition Test had decreased significantly
  • Severe multi-domain: 212 patients (17.5%) whose performance in the selective memory test, the Stroop color and word test, the symbol-digit modality test, the auditory serial addition test and word list generation had decreased significantly

Patients with conserved cognition and phenotypes of mild verbal memory / semantic fluence were younger and had a shorter illness duration (mean age 36.5 years and 38.2 years; mean illness duration 8.0 years and 8.3 years) in comparison to patients with mild diseases – multidomain (mean age 42.6 years; mean disease duration 12.8 years; P <0.001), severe executive / attention (mean age 42.9 years; mean disease duration 12.2 years; P <0.001) and severe multidomain phenotypes (mean age 44.0 years; mean disease duration 13.3 years; P <0.001).

The relative frequencies of phenotypes with severe executive / attention (11%, 14% and 19%, respectively) and severe multi-domain (12%, 18% and 36%) decreased from early relapsing-remitting MS to late-progressive to relapsing-remitting MS to secondary progressive MS.

On MRI, patients with mild verbal memory / semantic fluence had decreased hippocampal volume compared to patients with preserved cognition, patients with a mild multidomain phenotype had decreased cortical gray matter, and patients with severe executive / attention had a higher mean T2- hyperintense lesion volume, and those with severe multidomain phenotype had decreased volume in most brain structures.

The study had several limitations, including cross-sectional design, with the data being based on a clinical sample that may not be representative of the general MS population and completing the MRI exam in only a subset of patients.

“These phenotypes can provide a more meaningful measure of the cognitive status of MS patients and can help define clinical disabilities, help clinicians choose treatment, and tailor cognitive rehabilitation strategies,” the study’s researchers concluded.


De Meo E., Portaccio E., Giorgio A. et al. Identification of the different cognitive phenotypes in multiple sclerosis. JAMA Neurol. Published online January 4, 2021. doi: 10.1001 / jamaneurol.2020.4920

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