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Area of Science:

  • Neuroimaging
  • Neurodegeneration
  • Multiple Sclerosis (MS)

Background:

  • Brain-predicted age difference (brain-PAD) is a marker of neurodegeneration in people with multiple sclerosis (pwMS), linked to increased disability and cognitive impairment.
  • The influence of disease-modifying factors (DMFs) on brain-PAD and their mediating role in disability and cognition is not well understood.

Purpose of the Study:

  • To investigate the impact of DMFs on brain-PAD in pwMS.
  • To determine if brain-PAD mediates the effects of DMFs on disability and cognitive function in pwMS, using a same-age cohort to control for calendar age.

Main Methods:

  • Brain age was predicted from MRI scans; brain-PAD was calculated as the difference between predicted and chronological age.
  • Disability was assessed using EDSS, 9-hole peg test (9HPT), and timed 25-foot walk test (T25FWT). Cognitive function was evaluated using the Minimal Assessment of Cognitive Function in MS battery.
  • DMFs including smoking, alcohol consumption, physical activity, BMI at 18 years, diet, leisure, and education were analyzed. Linear regression and mediation analyses were employed.

Main Results:

  • Smoking, alcohol consumption, and BMI at 18 years were associated with increased brain-PAD.
  • Higher physical activity was linked to lower brain-PAD.
  • Mediation analyses confirmed that brain-PAD mediates the effects of smoking and alcohol on disability (EDSS, 9HPT, T25FWT) and cognition. Physical activity's effects on disability and cognition were also mediated by brain-PAD.

Conclusions:

  • DMFs unrelated to MS, particularly smoking, alcohol use, and BMI at 18 years, accelerate brain aging in pwMS.
  • Brain-PAD acts as a mediator, linking these lifestyle factors to increased disability and cognitive decline.
  • Lifestyle interventions targeting these DMFs may help mitigate neurodegeneration and preserve function in pwMS.