Efficacy of cognitive rehabilitation in cognition and brain networks: A randomised clinical trial in patients with multiple sclerosis

Abstract

Cognitive rehabilitation; Multiple sclerosis; Structural networks

Rehabilitació cognitiva; Esclerosi múltiple; Xarxes estructurals

Rehabilitación cognitiva; Esclerosis múltiple; Redes estructurales

This study evaluated the efficacy of the computerised Guttmann, NeuroPersonalTrainer® (GNPT) cognitive rehabilitation (CR) and characterised the induced changes in cerebral networks in patients with multiple sclerosis (MS). This multicentre, double-blind, randomised clinical trial compared upward intensity training (active treatment) to low-intensity static training (static treatment). Cognition was assessed using the Brief Repeatable battery before and after 12 weeks of training and at 10-months follow-up, and patients were classified as having a mild or severe cognitive impairment (CI). Brain MRI pre- and post-CR were analysed using an advanced tractography algorithm, based on multishell diffusion MRI, to obtain node-based graph metrics (local efficiency and strength) from microscopic fractional anisotropy. Seventy MS patients completed the study (age 48.9 ± 8.8, disease duration 16.8 ± 9.0 years); active treatment: 36, static treatment: 34. Verbal memory improved significantly post-CR in both groups (55 % active; 34 % static treatment), accompanied by increases in local efficiency and strength in multimodal regions. At follow-up, verbal memory declined in both groups but remained above the pre-CR assessment (−25 % and −17 %, respectively). Patients with severe-CI (n = 36) showed improvement only with active treatment, while those with mild-CI (n = 34) improved regardless of intensity treatment. Network changes were more pronounced in patients in active treatment and in those with severe-CI. Quality of life did not change at post-CR, and cognitive improvement was influenced by cognitive reserve (p = 0.011). In MS, GNPT temporarily improves verbal memory and increases network connectivity, reinforcing the CR as a valuable tool for enhancing cognitive skills and promoting neuronal plasticity.

This work was sponsored by the Instituto Carlos III (ISCIII) and co-funded by the European Union through the Plan Estatal de Investigación Científica y Técnica y de Innovación 2015–2024 (PI15/00587 to SL and AS; PI18/01030 to SL and AS; PI21/01189 to SL and AS), by AGAUR SGR-Cat 2021, by the Red Española de Esclerosis Múltiple (REEM − RD16/0015/0002, RD16/0015/0003), by Bristol-Myers Squibb, the Ayudas Merck de Investigación 2017 from the Fundación Merck Salud and the Proyecto Societat Catalana Neurologia 2017.