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

Abstract 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 an...

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Main Authors: Ermelinda De Meo, Emilio Portaccio, Rosa Cortese, Luis Ruano, Benedetta Goretti, Claudia Niccolai, Francesco Patti, Clara Chisari, Paolo Gallo, Paola Grossi, Angelo Ghezzi, Marco Roscio, Flavia Mattioli, Chiara Stampatori, Marta Simone, Rosa Gemma Viterbo, Raffaello Bonacchi, Assunta Maria Rocca, Elisa Leveraro, Antonio Giorgio, Nicola De Stefano, Massimo Filippi, Matilde Inglese, Maria Pia Amato
Format: Article
Language:English
Published: Wiley 2025-03-01
Series:Annals of Clinical and Translational Neurology
Online Access:https://doi.org/10.1002/acn3.52291
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author Ermelinda De Meo
Emilio Portaccio
Rosa Cortese
Luis Ruano
Benedetta Goretti
Claudia Niccolai
Francesco Patti
Clara Chisari
Paolo Gallo
Paola Grossi
Angelo Ghezzi
Marco Roscio
Flavia Mattioli
Chiara Stampatori
Marta Simone
Rosa Gemma Viterbo
Raffaello Bonacchi
Assunta Maria Rocca
Elisa Leveraro
Antonio Giorgio
Nicola De Stefano
Massimo Filippi
Matilde Inglese
Maria Pia Amato
author_facet Ermelinda De Meo
Emilio Portaccio
Rosa Cortese
Luis Ruano
Benedetta Goretti
Claudia Niccolai
Francesco Patti
Clara Chisari
Paolo Gallo
Paola Grossi
Angelo Ghezzi
Marco Roscio
Flavia Mattioli
Chiara Stampatori
Marta Simone
Rosa Gemma Viterbo
Raffaello Bonacchi
Assunta Maria Rocca
Elisa Leveraro
Antonio Giorgio
Nicola De Stefano
Massimo Filippi
Matilde Inglese
Maria Pia Amato
author_sort Ermelinda De Meo
collection DOAJ
description Abstract 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.
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spelling doaj-art-8e680d810d384d058c7769e7adf71a672025-08-20T03:42:39ZengWileyAnnals of Clinical and Translational Neurology2328-95032025-03-0112351252210.1002/acn3.52291Pediatric, adult, and late onset multiple sclerosis: Cognitive phenotypes and gray matter atrophyErmelinda De Meo0Emilio Portaccio1Rosa Cortese2Luis Ruano3Benedetta Goretti4Claudia Niccolai5Francesco Patti6Clara Chisari7Paolo Gallo8Paola Grossi9Angelo Ghezzi10Marco Roscio11Flavia Mattioli12Chiara Stampatori13Marta Simone14Rosa Gemma Viterbo15Raffaello Bonacchi16Assunta Maria Rocca17Elisa Leveraro18Antonio Giorgio19Nicola De Stefano20Massimo Filippi21Matilde Inglese22Maria Pia Amato23Department of Neuroinflammation, Institute of Neurology Univeristy College of London London UKNEUROFARBA Department, Neurosciences Section University of Florence Florence ItalyDepartment of Medicine, Surgery and Neuroscience University of Siena Siena ItalyEPIUnit, Instituto de Saúde Pública de Universidade do Porto Porto PortugalDepartment of Neuroinflammation, Institute of Neurology Univeristy College of London London UKDepartment of Neuroinflammation, Institute of Neurology Univeristy College of London London UKUniversity of Catania Catania ItalyUniversity of Catania Catania ItalyUniversity of Padova Padova ItalyDepartment, ASST Crema, Neuroimmunology Center, Cardiocerebrovascular Crema ItalyGallarate Hospital Varese ItalyGallarate Hospital Varese ItalyASST Spedali Civili Brescia Neuropsychology Unit Brescia ItalyASST Spedali Civili Brescia Neuropsychology Unit Brescia ItalyDepartment of Basic Medical Sciences, Child and Adolescence Neuropsychiatry Unit Neuroscience and Sense Organs University “Aldo Moro” Bari Bari ItalyDepartment of Basic Medical Sciences, Child and Adolescence Neuropsychiatry Unit Neuroscience and Sense Organs University “Aldo Moro” Bari Bari ItalyNeuroradiology Unit IRCCS San Raffaele Scientific Institute Milan ItalyNeuroimaging Research Unit IRCCS San Raffaele Scientific Institute MilanDepartment of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health University of Genoa Genoa ItalyDepartment of Medicine, Surgery and Neuroscience University of Siena Siena ItalyDepartment of Medicine, Surgery and Neuroscience University of Siena Siena ItalyNeuroimaging Research Unit IRCCS San Raffaele Scientific Institute MilanDepartment of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health University of Genoa Genoa ItalyNEUROFARBA Department, Neurosciences Section University of Florence Florence ItalyAbstract 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.https://doi.org/10.1002/acn3.52291
spellingShingle Ermelinda De Meo
Emilio Portaccio
Rosa Cortese
Luis Ruano
Benedetta Goretti
Claudia Niccolai
Francesco Patti
Clara Chisari
Paolo Gallo
Paola Grossi
Angelo Ghezzi
Marco Roscio
Flavia Mattioli
Chiara Stampatori
Marta Simone
Rosa Gemma Viterbo
Raffaello Bonacchi
Assunta Maria Rocca
Elisa Leveraro
Antonio Giorgio
Nicola De Stefano
Massimo Filippi
Matilde Inglese
Maria Pia Amato
Pediatric, adult, and late onset multiple sclerosis: Cognitive phenotypes and gray matter atrophy
Annals of Clinical and Translational Neurology
title Pediatric, adult, and late onset multiple sclerosis: Cognitive phenotypes and gray matter atrophy
title_full Pediatric, adult, and late onset multiple sclerosis: Cognitive phenotypes and gray matter atrophy
title_fullStr Pediatric, adult, and late onset multiple sclerosis: Cognitive phenotypes and gray matter atrophy
title_full_unstemmed Pediatric, adult, and late onset multiple sclerosis: Cognitive phenotypes and gray matter atrophy
title_short Pediatric, adult, and late onset multiple sclerosis: Cognitive phenotypes and gray matter atrophy
title_sort pediatric adult and late onset multiple sclerosis cognitive phenotypes and gray matter atrophy
url https://doi.org/10.1002/acn3.52291
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