Abstract
Cognitive impairment (CI) is frequently present in multiple sclerosis patients. Despite ongoing research, the neurological substrates have not been fully elucidated. In this study we investigated the contribution of gray and white matter in the CI observed in mildly disabled relapsing-remitting multiple sclerosis (RRMS) patients. For that purpose, 30 patients with RRMS (median EDSS = 2), and 30 age- and sex-matched healthy controls were studied. CI was assessed using the symbol digit modalities test (SDMT) and the memory alteration test. Brain magnetic resonance imaging, diffusion tensor imaging (DTI), voxel-based morphometry (VBM), brain segmentation, thalamic vertex analysis, and connectivity-based thalamic parcellation analyses were performed. RRMS patients scored significantly lower in both cognitive tests. In the patient group, significant atrophy in the thalami was observed. Multiple regression analyses revealed associations between SDMT scores and GM volume in both hemispheres in the temporal, parietal, frontal, and occipital lobes. The DTI results pointed to white matter damage in all thalamocortical connections, the corpus callosum, and several fasciculi. Multiple regression and correlation analyses suggested that in RRMS patients with mild disease, thalamic atrophy and thalamocortical connection damage may lead to slower cognitive processing. Furthermore, white matter damage at specific fasciculi may be related to episodic memory impairment.
Highlights
Multiple sclerosis (MS) is the most prevalent chronic inflammatory disease of the central nervous system
The present study investigated whether the cognitive impairment (CI) observed in mildly disabled relapsing-remitting multiple sclerosis (RRMS) patients might be caused by a combined loss of white matter integrity and gray matter atrophy, both in specific brain areas
This study investigated whether damage to specific white matter (WM) tracts and gray matter areas could be responsible for the CI observed in mildly disabled relapsingremitting multiple sclerosis (RRMS) patients
Summary
Multiple sclerosis (MS) is the most prevalent chronic inflammatory disease of the central nervous system. In MS, CI starts early in the disease course and generally worsens over time. It is influenced by many factors such as genetics, sex, intelligence, disease course, and health-promoting behaviors [2]; and may differ significantly between progressive vs. Thalamic atrophy is one of the earliest and most prominent signs of MS, with progressive atrophy detected in all MS types [8]. It is associated with CI and the progression of disability, and its detection may aid in the identification of patients with MS at greater risk of cognitive decline [9]. Thalamic volume has been suggested as a potential biomarker for CI detection, as it can be relatively measured [10,11]
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