Impact of Disease-modifying Therapies on Cognitive Function and Brain Atrophy in Relapsing-Remitting Multiple Sclerosis: A Systematic Review
Marianna Leite1, Ana Luiza Morgado Costa2, Ana Maria Porto Laxe Martins da Silva2, Gabriel Thomaz Candido2, Lizen Clare André Moreira2, Carolina Moura3, Nathane Braga2, Viviane Carvalho2, Raquel Molina2, Gutemberg Santos2
1Faculdade Santa Marcelina, 2Universidade Federal Fluminense, 3Hospital Universitário Antonio Pedro
Objective:
To synthesize evidence on the impact of disease-modifying therapies (DMTs) on cognitive function in multiple sclerosis (MS), comparing various treatments, including natalizumab, fingolimod, and other agents, in terms of their ability to preserve cognitive health and limit atrophy.
Background:
Cognitive impairment is common in multiple sclerosis (MS). While disease-modifying therapies (DMTs) help reduce relapses, their effect on cognitive function and brain atrophy is less clear.
Design/Methods:
This systematic review, conducted according to PRISMA guidelines, evaluated the impact of disease-modifying therapies (DMTs) on cognitive function in relapsing-remitting multiple sclerosis (RRMS) using validated cognitive tests, including the Paced Auditory Serial Addition Test (PASAT) and Symbol Digit Modalities Test (SDMT). Eligible studies measured cognitive outcomes, brain atrophy progression through MRI.
Results:
Six studies were included, with 1909 patients. Most patients maintained stable cognitive performance over one year of DMT treatment, regardless of the drug. Fingolimod and natalizumab both reduced relapse rates and improved cognitive scores after two years. However, natalizumab demonstrated greater efficacy in reducing MRI activity and achieving no evidence of disease activity (NEDA-3) compared to fingolimod. Both drugs mitigated, but did not prevent, brain atrophy progression. Natalizumab was associated with a reduction in cortical gray matter and thalamic atrophy compared to historical placebo data, supporting its potential neuroprotective effects. Ocrelizumab improved the Multiple Sclerosis Functional Composite score. Cognitive performance improvements observed on tests like the Paced Auditory Serial Addition Test (PASAT) were influenced by practice effects, requiring cautious interpretation.
Conclusions:
Natalizumab appears to offer the most benefit for preserving cognitive function and limiting lesion accumulation and brain atrophy, particularly in the thalamus and gray matter. Fingolimod also provides cognitive benefits, though with slightly less impact on MRI measures. DMT treatments underscore the importance of early and sustained DMT use to manage cognitive impairment in MS, though further long-term studies are warranted to confirm these findings.
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