Abstract
Objective: Cognitive impairment is an important feature in multiple sclerosis (MS) and has been associated to several Magnetic Resonance Imaging (MRI) markers, but especially brain atrophy. However, the relationship between specific neuropsychological tests examining several cognitive functions and brain volumes has been little explored. Furthermore, because MS frequently damage subcortical regions, it may be an interesting model to examine the role of subcortical areas in cognitive functioning. Our aim was to identify correlations between specific brain regions and performance in neuropsychological tests evaluating different cognitive functions in a large series of patients with MS.Methods: A total of 375 patients were evaluated with a comprehensive neuropsychological battery and with MRI. Voxel-based morphometry was conducted to analyse the correlation between cognitive performance and gray matter damage, using Statistical Parametric Mapping with the toolboxes VBM8 and Lesion Segmentation Tool.Results: The following correlations were found: Corsi block-tapping test with right insula; Trail Making Test with caudate nucleus, thalamus, and several cortical regions including the posterior cingulate and inferior frontal gyrus; Symbol Digit Modalities Test with caudate nucleus, thalamus, posterior cingulate, several frontal regions, insula, and cerebellum; Stroop Color and Word Test with caudate nucleus and putamen; Free and Cued Selective Reminding Test and Rey-Osterrieth Complex Figure with thalamus, precuneus, and parahippocampal gyrus; Boston Naming Test with thalamus, caudate nucleus, and hippocampus; semantic verbal fluency with thalamus and phonological verbal fluency with caudate nucleus; and Tower of London test with frontal lobe, caudate nucleus, and posterior cingulate.Conclusion: Our study provides valuable data on the cortical and subcortical basis of cognitive function in MS. Neuropsychological tests mainly assessing attention and executive function showed a stronger association with caudate volume, while tests primarily evaluating memory were more strongly correlated with the thalamus. Other relevant regions were the posterior cingulate/precuneus, which were associated with attentional tasks, and several frontal regions, which were found to be correlated with planning and higher order executive functioning. Furthermore, our study supports the brain vertical organization of cognitive functioning, with the participation of the cortex, thalamus, basal ganglia, and cerebellum.
Highlights
Multiple sclerosis (MS) is an acquired, demyelinating, and neurodegenerative disease of the central nervous system
One hundred and sixty-one patients (42.9%) had cognitive impairment. These patients had a lower level of education (14.42 ± 3.90 years of schooling vs. 15.70 ± 3.32, t = 3.329, p = 0.001), a greater lesion burden (24.16 ± 23.37 mL vs. 12.31 ± 15.32 mL, t = −5.590, p < 0.0001), a smaller raw gray matter volume (545 ± 67 vs. 563 ± 57, t = 2.817, p = 0.001), and a smaller normalized gray matter volume (0.405 ± 0.032 vs. 0.419 ± 0.027, t = 4.298, p < 0.0001)
Lesion burden was moderately correlated with the Symbol Digit Modalities Test (SDMT) (r = −0.462) and the Total Free Recall score in the Free and Cued Selective Reminding Test (FCSRT) (r = −0.449), and only weakly correlated with the remaining tests except for the Rey-Osterrieth Complex Figure (ROCF) and Tower of London-Drexel version (ToL), the latter with a very weak correlation
Summary
Multiple sclerosis (MS) is an acquired, demyelinating, and neurodegenerative disease of the central nervous system. Cognitive impairment is frequent and involves multiple functions, attention and executive function, memory, and information processing speed [1]. Other cognitive domains may be impaired, which explains the marked heterogeneity of these patients’ cognitive profiles [2]. Cognitive impairment has been associated with several MRI markers, including brain atrophy, lesion burden, lesions to white matter tracts, or normal-appearing white matter damage. Cognitive impairment has traditionally been considered to be more closely related to brain atrophy than to white matter lesion burden [3]. Other studies have associated cognitive dysfunction with other MRI findings, such as the number of cortical lesions, magnetization transfer ratio in gray matter, and white matter damage in diffusion tensor imaging [4,5,6,7]
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