An overview of the association between gray matter damage and cognitive impairment in multiple sclerosis

In multiple sclerosis (MS), cognitive impairment can be present in up to 70% of patients. Although pathological processes underlying cognitive impairment are complex, there is growing evidence that gray matter (GM) damage plays a crucial role in determining cognitive dysfunction. All forms of GM damage, namely GM volume loss, damage in the normal-appearing GM and cortical lesions have been found to be related to cognitive decline in patients with MS. GM can also be involved in cognitive impairment in the context of cortical reorganization, which is probably an adaptive phenomenon, the failure of which has been reported to be associated with cognitive impairment. In this review, the evidence for the involvement of GM damage in cognitive impairment in MS and the future directions of research are discussed.