Exploring the relation between reserve and fatigue in multiple sclerosis.

Introduction: Intellectual enrichment and brain reserve modulate the expression of cognitive and motor disability in multiple sclerosis (MS). Their association with fatigue, one of the most debilitating and common symptoms of MS, has never been explored.
Materials and Methods: Forty-eight MS patients underwent clinical and MRI examination at baseline and after 1 year. Physical and cognitive MS-related fatigue were evaluated via Modified Fatigue Impact subscales (MFIS-P and MFIS-C). Differences in reserve indexes between fatigued and non-fatigued patients were tested. The relationship between clinico-demographic features, global brain structural damage, indexes of reserve (age-adjusted intracranial volume and cognitive reserve index) and fatigue were tested via correlations and hierarchical linear/binary logistic regression, to predict MFIS-P and MFIS-C (at baseline) or new-onset fatigue and meaningful worsening in MFIS (at follow-up).
Results: At baseline, although a significant difference was identified for cognitive reserve questionnaire between fatigued and non-fatigued patients (18.19 ± 4.76 versus 15.15 ± 3.56, p = 0.015), only depression accounted for significant variance in MFIS-P and MFIS-C (R ² =0.248, p = 0.002; R ² =0.252, p<0.001). MFIS-T, MFIS-P and MFIS-C changes over time were associated to depression changes over time (r = 0.56, r = 0.55, and r = 0.57, respectively; all p<0.001). Indexes of reserve did not differ between non-fatigued patients and patients developing new-onset fatigue at follow-up. None of the baseline features was able to predict the new-onset fatigue or meaningful worsening in MFIS at follow-up.
Conclusions: Among the explored features, only depression was strongly associated to both physical and cognitive fatigue. Intellectual enrichment and brain reserve did not seem to affect fatigue symptoms in MS patients.
Competing Interests: Declaration of Competing Interest Antonio Carotenuto has received research grants from Almirall; honoraria form Novartis, Merck and Biogen; was supported by MAGNIMS/ECTRIMS research fellowship program. Giuseppe Pontillo was supported by MAGNIMS//ECTRIMS research fellowship program (2020) and ESNR research fellowship program (2021). Marcello Moccia has received research grants from the ECTRIMS-MAGNIMS, the UK MS Society, and Merck, and honoraria from Biogen, BMS Celgene, Ipsen, Merck, Novartis and Roche. Sirio Cocozza discloses Board Membership: Amicus Therapeutics; Payment for Lectures Including Service on Speakers Bureaus: Sanofi; Research Grants: FISM; Telethon. Roberta Lanzillo received personal compensation for speaking or consultancy from Biogen, Teva, Genzyme, Merck, Novartis, and Almirall. Vincenzo Brescia Morra has received honoraria from Almirall, Bayer, Biogen, Merck, Novartis, Roche and Sanofi Genzyme, and research grants from the Italian MS Foundation. Maria Petracca has received travel/meeting expenses from Novartis, Roche and Merck, speaking honoraria from HEALTH&LIFE S.r.l. and honoraria for consulting services from Biogen and research grants from Baroni Foundation. Mario Tranfa, Valentina Iuzzolino, Pierpaolo Perrella, Andrea Elefante and Arturo Brunetti have nothing to disclose.
(Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)