Journal
BIOLOGY OF SEX DIFFERENCES
Volume 11, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s13293-020-00326-3
Keywords
Multiple sclerosis; Sex differences; Neuroimaging; Neurodegeneration; Disability progression
Categories
Funding
- National Multiple Sclerosis Society [PP-1805-31001]
- NIH [RO1NS096748, RO1NS109670, R01NS086981]
- Conrad N. Hilton Foundation [17734, 18394]
- Tom Sherak MS Hope Foundation
- Rhoda Goetz Foundation
- Dunk MS Foundation
- German Federal Ministry of Health grant BMGBVA [2520FSB431]
- Brain Mapping Medical Research Organization
- Brain Mapping Support Foundation
- Pierson-Lovelace Foundation
- Ahmanson Foundation
- Capital Group Companies Charitable Foundation
- William M. and Linda R. Dietel Philanthropic Fund
- Northstar Fund
- National Center for Research Resources
- Office of the Director of the National Institutes of Health [C06RR012169, C06RR015431, S10OD011939]
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Background Women are more susceptible to multiple sclerosis (MS) than men by a ratio of approximately 3:1. However, being male is a risk factor for worse disability progression. Inflammatory genes have been linked to susceptibility, while neurodegeneration underlies disability progression. Thus, there appears to be a differential effect of sex on inflammation versus neurodegeneration. Further, gray matter (GM) atrophy is not uniform across the brain in MS, but instead shows regional variation. Here, we study sex differences in neurodegeneration by comparing regional GM atrophy in a cohort of men and women with MS versus their respective age- and sex-matched healthy controls. Methods Voxel-based morphometry (VBM), deep GM substructure volumetry, and cortical thinning were used to examine regional GM atrophy. Results VBM analysis showed deep GM atrophy in the thalamic area in both men and women with MS, whereas men had additional atrophy in the putamen as well as in localized cortical regions. Volumetry confirmed deep GM loss, while localized cortical thinning confirmed GM loss in the cerebral cortex. Further, MS males exhibited worse performance on the 9-hole peg test (9HPT) than MS females. We observed a strong correlation between thalamic volume and 9HPT performance in MS males, but not in MS females. Conclusion More regional GM atrophy was observed in men with MS than women with MS, consistent with previous observations that male sex is a risk factor for worse disease progression.
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