Pathology and MRI: exploring cognitive impairment in MS.

Cognitive impairment is a frequent symptom in people with multiple sclerosis, affecting up to 70% of patients. This article reviews the published association of cognitive dysfunction with neuroimaging findings. Cognitive impairment has been related to focal T2 hyperintense lesions, diffuse white matter damage and corical and deep gray matter atrophy. Focal lesions cannot sufficiently explain cognitive dysfunction in MS; microstructural tissue damage detectable by diffusion tensor imaging and gray matter atrophy are probably at least as relevant. Resting state functional magnetic resonance imaging is increasingly used to investigate the contribution of functional connectivity changes to cognitive function in MS. The fact that at least one third of MS patients are not overtly cognitively impaired despite significant radiographic tissue damage argues for protective factors (brain reserve, cognitive reserve) that require further clarification. It is concluded that the reported correlations between imaging findings and cognitive function do not imply causality. Well conceived and sufficiently powered longitudinal studies are lacking. Such studies would help unravel protective mechanisms against cogniitve decline and identify suitable imaging techniques to monitor cognitive function in individual patients with MS.