Pediatric, adult, and late onset multiple sclerosis: Cognitive phenotypes and gray matter atrophy

Abstract

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Objectives: We aim to investigate cognitive phenotype distribution and MRI correlates across pediatric-, elderly-, and adult-onset MS patients as a function of disease duration.

Methods: In this cross-sectional study, we enrolled 1262 MS patients and 238 healthy controls, with neurological and cognitive assessments. A subset of 222 MS patients and 92 controls underwent 3T-MRI scan for brain atrophy and lesion analysis. Multinomial probabilistic models identified likelihood of belonging to cognitive phenotypes (""preserved-cognition,"" ""mild verbal memory/semantic fluency,"" ""mild multi-domain,"" ""severe attention/executive,"" and ""severe multi-domain"") and experiencing MRI abnormalities based on disease duration and age at onset.

Results: In all groups, the likelihood of ""preserved-cognition"" phenotype decreased, whereas ""mild multi-domain"" increased with longer disease duration. In pediatric- and adult-onset patients, the likelihood of ""mild verbal memory/semantic fluency"" phenotypes decreased with longer disease duration, and that of ""severe multi-domain"" increased with longer disease duration. Only in adult-onset patients, the likelihood of ""severe executive/attention"" phenotype increased with longer disease duration. All groups displayed escalating probabilities of cortical, thalamic, hippocampal, and deep gray matter atrophy over disease course. Compared to adult, pediatric-onset patients showed lower probability of experiencing thalamic atrophy with longer disease duration, while elderly-onset showed higher probability of experiencing cortical and hippocampal atrophy.

Interpretation: Age at MS onset significantly influences the distribution of cognitive phenotypes and the patterns of regional gray matter atrophy throughout the disease course."