BrainAgeMS: protocol for a prospective comparative study of brain aging in healthy adults and people with multiple sclerosis

Biological brain aging can diverge substantially from chronological aging, particularly in chronic neurological conditions like multiple sclerosis (MS), where neuroinflammatory and neurodegenerative processes may accelerate age-related brain changes. This study aims to determine whether multipool Chemical Exchange Saturation Transfer (CEST) and T1 relaxometry at 7 T can serve as biologically grounded imaging markers of brain age in healthy adults and people with MS (pwMS). BrainAgeMS (NCT06221631) is a prospective, single-center, cross-sectional comparative study recruiting 200 participants aged 18–65 years: 100 healthy controls (HC) and 100 pwMS. All participants undergo blood sampling for biological age determination using the PhenoAge algorithm, motor, cognitive, and psychological assessments, and 7 T MRI featuring multipool CEST and T1 relaxometry. A brain age prediction model trained on HC data will be applied to pwMS to derive a brain age gap. The primary outcomes are the two brain-age gaps in pwMS: the differences between estimated brain age and (i) chronological age and (ii) PhenoAge. Secondary outcomes include associations of these gaps with disability, cognition, fatigue, and quality of life. If validated, these quantitative MRI markers could complement existing tools for MS disease monitoring and serve as outcome measures for future brain health interventions. Clinical Trial Registration https://clinicaltrials.gov/study/NCT06221631 , identifier NCT06221631