Brain-predicted Age Gap and Brain Volume Differences in Multiple Sclerosis: A Cross-sectional Study
Fen Bao1, Anas Nourelden1, Vivian Truong1, Nidhi Patel1, Abigail Biddix1, Mawadda Abdelhai1, Basil Memon2, Zaima Liaquat1, Carla Santiago-Martinez1, Yongsheng Chen1, Anza Memon3
1Neurology, Wayne State University, School of Medicine, 2Michigan State University; Wayne State University, School of Medicine, 3John D. Dingell, VAMC; Wayne State University, School of Medicine
Objective:
The aim of this study is to investigate brain-predicted age, brain-predicted age gap (the difference between brain-predicted age and chronological age), and brain tissue volume changes in Multiple Sclerosis (MS) patients compared to healthy controls (HCs) to better understand and characterize the neurodegenerative burden of the disease.
Background:
MS is a chronic autoimmune disease with neuroinflammation, demyelination, and neurodegeneration, leading to brain atrophy and cognitive impairment. Recent advances in neuroimaging have enabled the use of brain-predicted age, the difference between predicted and chronological age, as a biomarker to estimate brain aging. It has been linked to neurodegeneration but remains underexplored in MS.
Design/Methods:
This cross-sectional study included 33 HCs and 109 MS patients. Whole-brain MRI was performed using a SIEMENS 3T Verio system. Raw 3D T1-weighted images were processed with brainageR (v2.1) to estimate normalized tissue volumes and brain-predicted age using Gaussian process regression. Statistical analyses were performed in SPSS v29 to investigate the group differences using independent sample t-test and chi-square test (p<0.05).
Results:
No significant differences were observed in chronological age (35.46 ± 13.08 vs. 38.65 ± 8.51 years, p=0.194) or gender (60.61% vs. 66.06% females, p=0.566) between groups. Compared to HCs, MS patients had significantly older brain-predicted age (52.69 ± 12.54 vs. 35.00 ± 12.40 years, p<0.001) and larger age gap (14.04 ± 12.14 vs. -0.45 ± 4.45 years, p<0.001). MS patients also showed lower gray matter volume (617.90 ± 72.06 ml vs. 694.93 ± 75.81 ml, p<0.001), lower white matter volume (443.40 ± 54.50 ml vs. 472.66 ± 59.81 ml, p=0.009), and higher CSF volume (307.66 ± 115.35 ml vs. 247.00 ± 48.91 ml, p<0.001).
Conclusions:
MS patients exhibit accelerated brain aging with a larger brain-predicted age gap, reduced GM and WM, and increased CSF. Brain-predicted age and volumetric changes may serve as biomarkers of neurodegeneration in MS.
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