Background: Co-occurring walking and cognitive performance deficits are debilitating consequences of multiple sclerosis (MS) that worsen with age. However, it is unknown if fatigability influences such age-related worsening of walking and cognitive performance.

Objective: This cross-sectional study examined possible age-related differences in walking-related motor fatigability (incremental six-minute-walk (6MW) performance) and cognitive fatigability (incremental Symbol Digit Modalities Test (SDMT) performance) in adults with MS.

Methods: 196 adults with MS were categorized into age-groups: younger (20-39 years; n = 53), middle-aged (40-59 years; n = 89), and older (60-79 years; n = 54), and completed the 6MW and SDMT. Age-group differences in incremental 6MW and SDMT performance, controlling for disability status, were examined using separate, mixed-factor ANCOVAs.

Results: There were no statistically significant age-group-by-time interactions on walking-related motor or cognitive fatigability when controlling for disability. However, there were significant main effects of time on incremental 6MW (p = 0.01) and SDMT (p < 0.01) performance indicating the presence of walking-related motor and cognitive fatigability, respectively, collapsed across age-groups.

Conclusions: Fatigability does not exert a primary influence on age-related worsening of walking and cognitive neuroperformance outcomes among adults with MS. This suggests that walking-related motor fatigability and cognitive fatigability may not be optimal targets for mitigating age-related declines in ambulation and cognition among adults with MS.