Myelin Damage in Normal Appearing White Matter Contributes to Impaired Cognitive Processing Speed in Multiple Sclerosis

Abstract

BACKGROUND AND PURPOSE Cognitive impairment is a core symptom in multiple sclerosis (MS). Damage to normal appearing white matter (NAWM) is likely involved. We sought to determine if greater myelin heterogeneity in NAWM is associated with decreased cognitive performance in MS. METHODS A total of 27 participants with MS and 13 controls matched for age, sex, and education underwent myelin water imaging (MWI) from which the myelin water fraction (MWF) was calculated. Corpus callosum, superior longitudinal fasciculus, and cingulum were chosen as regions of interest (ROIs) a priori based on their involvement in MS‐related cognitive impairment. Cognitive performance was assessed using the Symbol Digit Modalities Test (SDMT). Pearson ́s product moment correlations were performed to assess relationships between cognitive performance and myelin heterogeneity (variance of MWF within an ROI). RESULTS In MS, myelin heterogeneity in all three ROIs was significantly associated with performance on the SDMT. These correlations ranged from moderate (r = −.561) to moderately strong (r = −.654) and were highly significant (P values ranged from .001 to .0002). Conversely, myelin heterogeneity was not associated with SDMT performance in controls in any ROI (P > .108). CONCLUSION Increased myelin heterogeneity in NAWM is associated with decreased cognitive processing speed performance in MS.

Nile Red fluorescence spectroscopy reports early physicochemical changes in myelin with high sensitivity

“…4E could more profoundly exacerbate conduction abnormalities along the length of any particular axon. These changes could, in turn, explain the frequent and disabling nonfocal symptoms affecting MS patients such as fatigue, cognitive impairment, and depression (51) and are consistent with diffusion tensor imaging abnormalities in the white matter of cognitively impaired MS patients (52).…”

T2-Pseudonormalization and Microstructural Characterization in Advanced Stages of Late-infantile Metachromatic Leukodystrophy

“…Changes in diffusion-based parameters, in particular NODDI and myelin water fraction and magnetization transfer ratio, were observed as well. These changes were correlated with disability, cognitive impairment, and the degree of brain atrophy in multiple sclerosis patients and therefore seem to play an important clinical role in the extent of disease symptoms [ 62 ]. The reported histopathological samples from such regions show axonal pathology and microglial activation depending on the distance to focal MS lesions [ 63 ].…”

Cervical cord myelin abnormality is associated with clinical disability in multiple sclerosis

“…Since MHI captures a change in mean and variance, it is more sensitive to myelin damage than using mean MWF alone, particularly in cross-sectional studies with limited sample size. Recently, Abel et al 20 showed that MWF variance was higher in MS and more consistent between healthy individuals than mean MWF. They also found an inverse relationship between myelin heterogeneity and cognitive processing speed performance in MS, which was not significant using the mean MWF.…”

“…They also found an inverse relationship between myelin heterogeneity and cognitive processing speed performance in MS, which was not significant using the mean MWF. 20 Furthermore, Wearn et al 21 proposed that T2 heterogeneity in the brain may be a superior measure than mean T2 to predict cognitive decline and to be used as an early marker of Alzheimer’s disease pathology. These past findings support that MHI may be a more sensitive metric to detect subtle alterations in cervical cord myelin that may not be evident with mean MWF measures alone.…”