Abstract
BackgroundCognitive impairment (CI) is a frequent and debilitating symptom in MS. To better understand the neural bases of CI in MS, this magnetic resonance imaging (MRI) study aimed to identify and quantify related structural brain changes and to investigate their relation to each other.MethodsWe studied 51 patients with CI and 391 patients with cognitive preservation (CP). We analyzed three-dimensional T1-weighted and FLAIR scans at 3 Tesla. We determined mean cortical thickness as well as volumes of cortical grey matter (GM), deep GM including thalamus, cerebellar cortex, white matter, corpus callosum, and white matter lesions (WML). We also analyzed GM across the whole brain by voxel-wise and surface-based techniques.ResultsMean disease duration was 5 years. Comparing MS patients with CI and CP, we found higher volumes of WML, lower volumes of deep and cortical GM structures, and lower volumes of the corpus callosum (all corrected p values < 0.05). Effect sizes were largest for WML and thalamic volume (standardized ß values 0.25 and − 0.25). By logistic regression analysis including both WML and thalamic volume, we found a significant effect only for WML volume. Inclusion of the interaction term of WML and thalamic volume increased the model fit and revealed a highly significant interaction of WML and thalamic volume. Moreover, voxel-wise and surface-based comparisons of MS patients with CI and CP showed regional atrophy of both deep and cortical GM independent of WML volume and overall disability, but effect sizes were lower.ConclusionAlthough several mechanisms contribute to CI already in the early stage of MS, WML seem to be the main driver with thalamic atrophy primarily intensifying this effect.
Highlights
Cognitive impairment (CI) is a common symptom in multiple sclerosis (MS)
Multiple Sclerosis Inventory Cognition (MuSIC) consists of 5 subtests to assess the cognitive core deficits in MS: attention and memory are tested first by ‘word list A’, second by ‘word list B’ and third by ‘word list A delayed’; mental set-shifting and cognitive information speed processing are tested by ‘verbal fluency’, inhibitory control is captured by a stroop test called ‘interference’
Performance in the cognitive screening test MuSIC was much lower in the 28 CI patients in which this test battery was available (20.4 ± 5.5 vs. cognitive preservation (CP) MS patients: 26.7 ± 2.9, p < 0.001)
Summary
Cognitive impairment (CI) is a common symptom in multiple sclerosis (MS). The neuropathological substrates of MS-related CI, and potential therapeutic targets, are still controversial [1]. To the best of our knowledge, reviewed the ten structural brain MRI studies on CI in MS, with the highest numbers of CI patients included [4,5,6,7,8,9,10,11,12,13], we observed inconsistent results with regard to the contribution of WML load and GM atrophy to CI in MS. Conclusion several mechanisms contribute to CI already in the early stage of MS, WML seem to be the main driver with thalamic atrophy primarily intensifying this effect
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