Limbic Pathway Correlates of Cognitive Impairment in Multiple Sclerosis

BACKGROUND AND PURPOSE: Distinct injuries to various limbic white matter pathways have been reported to be associated with different aspects of cognitive dysfunction in multiple sclerosis (MS). Diffusion tensor imaging (DTI) offers a noninvasive method to map tissue microstructural organization. We utilized quantitative magnetic resonance imaging methods to analyze the main limbic system—white matter structures in MS patients with cognitive impairment (CI). METHODS: Ten cognitively nonimpaired MS (MSNI) patients and 36 patients with diagnosed CI (MSCI) underwent the minimal assessment of Cognitive Function in MS (MACFIMS) battery. DTI measures of fornix, cingulum, uncinate fasciculus (UF) included tract volume and corresponding fractional anisotropy (FA), mean (MD), axial (AD), and radial (AD) diffusivities. These were statistically analyzed for associations with CI after adjusting for the confounders. RESULTS: Fornix FA and RD, left cingulum FA, MD, and RD, right cingulum FA, MD, and RD, and left UF FA showed significant differences between MSNI and MSCI (P <.001). Fornix FA (r = −.6) and RD (r =.52), and right cingulum FA (r = −.54) and RD (r =.5) correlated significantly with CI in regression analyses. CONCLUSIONS: The extent of disruption of microstructural disorganization in the main limbic pathways using DTI impacts the extent of CI seen in subjects with MS.