Sex Differences in Gray Matter Atrophy and White Matter Disruption Progression in Early Multiple Sclerosis
Abstract
Sex differences exist in multiple sclerosis (MS). Although women are more susceptible to MS than men by a ratio of approximately 3:1, studies have shown that men are at higher risk for worse disability, have worse cognitive decline, and demonstrated a shorter time to conversion from relapsing-remitting MS (RRMS) to secondary progressive MS (SPMS). Together, these studies suggest the possibility that men with MS may have a worse prognosis than women with MS. However, sex differences in whole brain size, structure volumes, and other measures have been shown during health and these differences in healthy brains are a confound in the study of sex differences in MS. For rigor in the study of sex as a biologic variable, this confound must be addressed. In a cross-sectional study, we compared female MS patients to female healthy controls and male MS patients to male healthy controls to remove the confound of known sex differences in healthy controls. We demonstrated more extensive gray matter (GM) loss in male MS patients than in female MS patients. In this proposal, we will determine sex differences over time in the progression of GM loss and white matter (WM) damage in early MS. We propose that male MS patients will exhibit more GM loss earlier than female MS patients, each compared to their respective healthy controls. We also expect that male MS patients will show WM damage earlier than female MS patients, again compared to their respective healthy controls. Disability differences exist in MS. MS is multifocal, characterized by distinct disabilities affecting cognition, vision, and fine motor control, to name a few. Individual MS patients exhibit a variable set of disabilities, with different rates of change in each disability over time. We have previously demonstrated distinct regions of GM loss that corresponded with specific disabilities in a cross-sectional study of RRMS patients. Here, we will create maps of GM loss and WM damage for cognition, vision, and fine motor control disabilities, and evaluate their change over time in female and male MS patients. We propose that distinct patterns of GM loss will be associated with worsening in specific disabilities and that these patterns will differ between female and male MS patients. Further, we propose that distinct patterns of WM damage will also be associated with worsening in specific disabilities, and that these patterns will be different between female and male MS patients. We will perform these experiments by leveraging data from an existing longitudinal dataset of early MS patients and healthy controls comprising 280 subjects (from our collaborators at Charité Universitätsmedizin Berlin) and using state-of-the-art image processing technologies. We believe that sex differences in disease progression may alter future clinical trial design and may inform clinician s decisions on treatment for their patients. Further, disability-specific maps will permit a more accurate measure of disability progression and may be a more sensitive biomarker for use during evaluation of future treatments targeting remyelination and neural repair.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310868
Entities
People
- Allan Mackenzie-graham
Organizations
- United States Army
- University of California, Los Angeles