Age Gap as a Biomarker of Neurodegeneration and Functional Decline in Multiple Sclerosis: Insights into Racial Differences
Anas Nourelden1, Fen Bao1, Mawadda Abdelhai1, Nidhi Patel1, Abigail Biddix1, Zaima Liaquat1, Kalyan Yarraguntla1, Jacob Rube1, Carla Santiago-Martinez1, Anza Memon2
1Neurology, Wayne State University, School of Medicine, 2Neurology, John D. Dingell, VAMC; Wayne State University, School of Medicine
Objective:
This study evaluates the relationship between age gap (brain-predicted minus chronological ages) and neurodegeneration, microstructural, clinical, and functional outcomes for the overall multiple sclerosis (MS) cohort and separately for Black and White patients.
Background:
Brain-predicted age, derived from neuroimaging, reflects cumulative neurodegeneration and may reveal disparities across racial groups in MS.
Design/Methods:
In this cross-sectional study, all patients underwent brain MRI on a SIEMENS 3T system and clinical assessments. 3D T1-weighted images were processed with brainageR (v2.1) using Gaussian process regression to estimate brain-predicted age and tissue volumes. Using SPSS v29, Spearman’s correlations tested associations between age gap and volumetric measures (GM, WM, CSF), lesion burden (T2 lesion volume), microstructural integrity, fractional anisotropy (FA) and mean diffusivity (MD), cognitive/motor performance (SDMT, 9HPT), and quality of life (MSQoL).
Results:
A total of 120 MS patients (59 Black, 61 White) were included. No significant differences were found in age (39.5 ± 9.2 vs. 43.0 ± 11.3 years, p=0.07) or gender (42 vs. 34 female patients, p=0.079) between Black and White MS patients. Age gap correlated negatively with GM (r=-0.443, p<0.001), WM (r=-0.256, p=0.005), and cortical thickness (r=-0.300, p=0.001), and positively with CSF (r=0.385, p<0.001) and lesion volume (r=0.721, p<0.001). Correlations were stronger in Black for GM and lesion volume. Larger age gaps were linked to reduced FA in NAGM (r=-0.458, p<0.001) and NAWM (r=-0.565, p<0.001), and higher MD (NAGM r=0.325, NAWM r=0.451, both p<0.001). Age gap correlated negatively with SDMT (r=-0.358, p=0.014) and positively with 9HPT-ND (r=0.325, p=0.030). Associations were stronger in White, especially for motor outcomes.
Conclusions:
Age gap is a robust marker of neurodegeneration in MS, correlating with atrophy, lesion burden, microstructural damage, and functional decline. Racial differences suggest Black patients show greater neurodegeneration, while White patients show stronger links with functional impairment.
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