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Background:  Magnetic Resonance Imaging (MRI) analysis method “brain-age” paradigm could offer an intuitive prognostic metric (brain-predicted age difference: brain-PAD) for disability in Multiple Sclerosis (MS), reflecting structural brain health adjusted for aging. Equally, cellular senescence has been reported in MS using T-cell biomarker CD8 + CD57 + .   Objective:  Here we explored links between MRI-derived brain-age and blood-derived cellular senescence. We examined the value of combining brain-PAD with CD8 + CD57 + (ILT2 + PD-1 + ) T-cells when predicting disability score in MS and considered whether age-related biological mechanisms drive disability.   Methods:  Brain-age analysis was applied to T1-weighted MRI images. Disability was assessed and peripheral blood was examined for CD8 + CD57 +  T-cell phenotypes. Linear regression models were used, adjusted for sex, age and normalized brain volume.   Results:  We included 179 mainly relapsing-remitting MS patients. A high brain-PAD was associated with high physical disability (mean brain-PAD = +6.54 [5.12–7.95]). CD8 + CD57 + (ILT2 + PD-1 + ) T-cell frequency was neither associated with disability nor with brain-PAD. Physical disability was predicted by the interaction between brain-PAD and CD8 + CD57 + ILT2 + PD-1 +  T-cell frequency ( AR  2  = 0.196), yet without improvement compared to brain-PAD alone ( AR  2  = 0.206; AICc = 1.8).   Conclusion:  Higher frequency of CD8 + CD57 + ILT2 + PD-1 +  T-cells in the peripheral blood in patients with an older appearing brain was associated with worse disability scores, suggesting a role of these cells in the development of disability in MS patients with poorer brain health.

Worse Physical Disability Is Associated With the Expression of PD-1 on Inflammatory T-Cells in Multiple Sclerosis Patients With Older Appearing Brains