# Contribution of Gray and White Matter Abnormalities to Cognitive Impairment in Multiple Sclerosis
## 3 Discussion
However, no significant difference in GM volume was found between CI and CP patients in [PERSON]'s study, and the authors proposed that GM was not related to cognitive deficits in MS [10]. The current results revealed significant decreased GM volume, including in the right temporal lobe, left insula and bilateral caudate nucleus in CI patients compared with CP patients. The caudate nucleus has been found to be related to verbal fluency, language learning and memory [25], and the temporal lobe is implicated in memory function and information processing speed [12; 24; 26]. The current results indicate that atrophy of the right temporal pole, left insula and bilateral caudate nucleus may be related to CI in RRMS. The discrepancy may be related to the different disease subtypes of MS patients between the two studies. In addition, the results revealed that CI-MS patients had a lower educational level, as well as more severe clinical disability and mental dysfunction, including anxiety and depression, compared with CP-MS patients. These findings are consistent with several previous reports suggesting that lower educational level, higher Expanded Disability Status Scale (EDSS)score and more severe mental dysfunction are related to CI [27; 28; 29]. A 5-year neuropsychological longitudinal study of patients with MS reported no significant change in the speed of information processing in a group of patients with more than 14 years of education, whereas patients with less than 14 years of education exhibited significant declines in information processing speed [30]. Similarly, a recent 4.5-year follow-up study indicated that increased intellectual enrichment contributed to resilience against disease-related cognitive decline [31]. In addition, compared with CP-MS patients, CI-MS patients exhibited more severe physical disabilities and abnormal moods including anxiety and depression. Previous studies reported that fatigue and abnormal mood, particularly depression, can affect patients' cognitive function, quality of life and medical compliance [27; 32]. Taken together, these findings highlight the importance of treatment for abnormal mood, particularly depression, among MS patients. The present study involved several limitations. First, the CI patient sample size was relatively small; Second, the study did not implement a uniform set of criteria for distinguishing CI-MS patients. Most previous studies used >1.5 or 2 standard deviations (SDs) below normal data in at least two cognitive domains for identifying CI. In the current study, we used 1.5 SDs as the threshold, to enable the detection of mild CI; Third, this was a single center study. Since all patients were enrolled in the study via tertiary referrals, selection bias may have caused the sample to be non-representative of the wider population. It would be useful for future studies involving multiple centers and a larger study population to validate the current results. In addition, future studies should use more strict criteria for identifying CI (e.g., >2 SDs, or impairment in at least three cognitive domains). It should be noted that cortical lesions were not measured in our studies and lesion-filling was not implemented either. Previous investigations have shown that lesion-filling could improve the accuracy of WM and GM volume measurements [33]. However, there is controversy about the lesion filling approach in MS. Some researchers have argued that hypointensity WM lesions in MS could be misclassified as GM in tissue segmentation that increase the measured GM volume [34; 35]. In contrast, some others believe that all GM volumes except for hippocampus had smaller volumes in the original image compared to the lesion-filled image in MS patients [36]. Moreover, lesion volumes were usually identified manually, and this process might increase the subjective errors.