Neuropsychology and Cognition Oral Presentation

YI02.03 - Identifying distinct cognitive phenotypes in multiple sclerosis 

  • E. De Meo
  • E. De Meo
  • E. Portaccio
  • A. Giorgio
  • L. Ruano
  • B. Goretti
  • C. Niccolai
  • F. Patti
  • C. Chiasari
  • P. Gallo
  • P. Grossi
  • A. Ghezzi
  • M. Roscio
  • F. Mattioli
  • C. Stampatori
  • M. Simone
  • R. Viterbo
  • M. Rocca
  • N. De Stefano
  • M. Filippi
  • M. Amato
Presentation Number
Presentation Topic
Neuropsychology and Cognition
Lecture Time
11:39 - 11:51



Cognitive impairment is one of the most disabling symptoms of multiple sclerosis (MS), affecting about 50% of patients.


We sought to define homogeneous cognitive phenotypes in a large cohort of MS patients by using a data-driven approach, and to assess their distinctive clinical and MRI features.


A cohort of 1212 MS patients and 196 healthy controls (HC) from 8 Italian MS centers underwent cognitive evaluation with Rao’s Brief Repeatable Battery and Stroop Color Word Test. A subgroup (172 MS patients and 50 HC) also underwent a 3T MRI examination, including 3D T1-weighted and dual-echo sequences. Latent-profile analysis was used on cognitive tests’ z-scores for identifying cognitive phenotypes. Linear regression and mixed effects models were used to define the clinical and MRI features of each phenotype.


Five cognitive phenotypes were identified, characterized by “preserved-cognition” (19%), “mild verbal memory/semantic fluency” impairment (30%), “mild-multi-domain” impairment (19%), “severe-attention/executive” impairment with mild impairment of other domains (14%), and “severe-multi-domain” impairment (18%). “Preserved-cognition” patients had shorter disease duration and lower Expanded Disability Status Scale (EDSS) score than all other groups, and mildly impaired phenotypes included patients with shorter disease duration and less likely progressive disease compared to severely impaired groups. However, the “preserved-cognition” group also included patients with progressive disease and high EDSS scores, and severely impaired phenotypes were also represented in early MS stages. Comparing each phenotype to “preserved-cognition” group, distinctive MRI features emerged: “mild verbal memory/semantic fluency” patients had reduced hippocampal volume (p=0.02), “mild-multi-domain” reduced cortical gray matter volume (p=0.04), “severe-attention/executive” higher lesion volume (p=0.04) and severe-multi-domain” extensive brain damage (p<0.01 for lesion, brain, gray matter and thalamic volumes).


We identified five cognitive phenotypes of MS patients, with distinctive MRI substrates. By defining homogenous and clinically meaningful groups, this characterization may be useful for future research on cognitive impairment in MS, and for defining personalized management approaches and rehabilitative strategies in clinical practice.