Research Article| Volume 42, 102136, July 2020

Walking and cognitive performance in adults with multiple sclerosis: Do age and fatigability matter?


      • Ambulation and cognition worsen with age in adults with multiple sclerosis (MS).
      • Fatigability might influence such age-related worsening of ambulation and cognition.
      • This study tested possible age-group differences in fatigability in adults with MS.
      • There were no significant age-group differences in walking/cognitive fatigability.
      • Fatigability may not explain age-related declines in walking and cognition in MS.



      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.


      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.


      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.


      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.


      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.


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        • Baird J.F.
        • Cederberg K.L.J.
        • Sikes E.M.
        • et al.
        Changes in cognitive performance with age in adults with multiple sclerosis.
        Cogn. Behav. Neurol. 2019; 32: 201-207
        • Baird J.F.
        • Cederberg K.L.J.
        • Sikes E.M.
        • et al.
        Physical activity and walking performance across the lifespan among adults with multiple sclerosis.
        Mult. Scler.Relat. Disord. 2019; 35: 36-41
        • Benedict R.H.
        • DeLuca J.
        • Phillips G.
        • et al.
        Validity of the Symbol Digit Modalities Test as a cognition performance outcome measure for multiple sclerosis.
        Mult. Scler. 2017; 23: 721-733
        • Benedict R.H.B.
        • Holtzer R.
        • Motl R.W.
        • et al.
        Upper and lower extremity motor function and cognitive impairment in multiple sclerosis.
        J. Int. Neuropsychol. Soc. 2011; 17: 643-653
        • Bollaert R.
        • Motl R.W
        Physical and cognitive functions, physical activity, and sedentary behavior in older adults with multiple sclerosis.
        J. Geriatr. Phys. Ther. 2019; 42: 304-312
        • Bollaert R.E.
        • Balto J.M.
        • Sandroff B.M.
        • et al.
        Preliminary evidence for the effects of aging and multiple sclerosis on cognitive performance: an analysis based on effect size estimates.
        Exp. Aging Res. 2017; 43: 346-354
        • Bollaert R.E.
        • Sandroff B.M.
        • Stine-Morrow E.A.L.
        • et al.
        The intersection of physical function, cognitive performance, aging, and multiple sclerosis: a cross-sectional comparative study.
        Cogn. Behav. Neurol. 2019; 32: 1-10
        • Branco M.
        • Ruano L.
        • Portaccio E.
        • et al.
        Aging with multiple sclerosis: prevalence and profile of cognitive impairment.
        Neurol. Sci. 2019; 40: 1651-1657
        • Chaudhuri A.
        • Behan P.
        Fatigue in neurological disorders.
        Lancet. 2004; 363: 978-988
        • Cohen J.
        Statistical Power Analysis For the Behavioral Sciences.
        second ed. Lawrence Erlbaum, Hillsdale, NJ1988
        • Dalgas U.
        • Kjolhede T.
        • Gijbels D.
        • et al.
        Aerobic intensity and pacing pattern during the six-minute walk test in patients with multiple sclerosis.
        J. Rehab. Med. 2014; 46: 59-66
        • DeLuca J.
        Fatigue As a Window to the Brain.
        MIT Press, London2005
        • Gijbels D.
        • Dalgas U.
        • Romberg A.
        • et al.
        Which walking capacity tests to use in multiple sclerosis? A multicentre study providing the basis for a core set.
        Mult. Scler. 2011; 18: 364-371
        • Goldman M.D.
        • Marrie R.A.
        • Cohen J.A
        Evaluation of the six-minute walk in multiple sclerosis subjects and healthy controls.
        Mult. Scler. 2008; 14: 383-390
        • Hadjimichael O.
        • Kerns R.D.
        • Rizzo M.A.
        • Cutter G.
        • Vollmer T
        Persistent pain and uncomfortable sensations in persons with multiple sclerosis.
        Pain. 2007; 127: 35-41
        • Holtzer R.
        • Foley F.
        • D’Orio
        • et al.
        Learning and cognitive fatigue trajectories in multiple sclerosis defined using a burst measurement design.
        Mult. Scler. 2013; 19: 1518-1525
        • Kluger B.M.
        • Krupp L.B.
        • Enoka R.M
        Fatigue and fatigability in neurologic illnesses: proposal for a unified taxonomy.
        Neurology. 2013; 80: 409-416
        • Krupp L.B.
        Fatigue in multiple sclerosis: definition, pathophysiology and treatment.
        CNS Drugs. 2003; 17: 225-234
        • Learmonth Y.C.
        • Motl R.W.
        • Sandroff B.M.
        • et al.
        Validation of patient determined disease steps (PDDS) scale scores in persons with multiple sclerosis.
        BMC Neurol. 2013; 13: 37
        • Leone C.
        • Severijns D.
        • Doležalová V.
        • et al.
        Prevalence of walking-related motor fatigue in persons with multiple sclerosis: decline in walking distance induced by the 6-minute walk test.
        Neurorehabil. Neural Repair. 2016; 30: 373-383
        • Linnhoff S.
        • Fiene M.
        • Heinze H.J.
        • et al.
        Cognitive fatigue in multiple sclerosis: an objective approach to diagnosis and treatment by transcranial electrical stimulation.
        Brain Sci. 2019; 9: 100
        • Morrow S.A.
        • Rosehart H.
        • Johnson A.M
        Diagnosis and quantification of cognitive fatigue in multiple sclerosis.
        Cogn. Behav. Neurol. 2015; 28: 27-32
        • Phan-Ba R.
        • Calay P.
        • Grodent P.
        • et al.
        Motor fatigue measurement by distance-induced slow down of walking speed in multiple sclerosis.
        PLoS ONE. 2012; 7: e34744
        • Ramari C.
        • Moraes A.G.
        • Tauil C.B.
        • et al.
        Knee flexor strength and balance control impairment may explain declines during prolonged walking in women with mild multiple sclerosis.
        Mult. Scler. Relat. Disord. 2018; 20: 181-185
        • Roy S.
        • Frndak S.
        • Drake A.
        • et al.
        Differential effects of aging on motor and cognitive functioning in multiple sclerosis.
        Mult. Scler. 2016; 23: 1385-1393
        • Samkoff L.M.
        • Goodman A.D.
        Symptomatic management in multiple sclerosis.
        Neurol. Clin. 2011; 29: 449-463
        • Sanai A.
        • Saini V.
        • Benedict R.H.B.
        • et al.
        Aging and multiple sclerosis.
        Mult. Scler. 2016; 22: 717-725
        • Schwid S.R.
        • Tyler C.M.
        • Scheid E.A.
        • et al.
        Cognitive fatigue during a test requiring sustained attention: a pilot study.
        Mult. Scler. 2003; 9: 503-508
        • Sehle A.
        • Mündermann A.
        • Starrost K.
        • et al.
        Objective assessment of motor fatigue in multiple sclerosis using kinematic gait analysis: a pilot study.
        J. Neuroeng. Rehabil. 2011; 8: 59
        • Simonsick E.M.
        • Schrack J.A.
        • Glynn N.W.
        • et al.
        Assessing fatigability in mobility-intact older adults.
        J. Am. Geriatr. Soc. 2014; 62: 347-351
        • Smith A
        Symbol Digit Modalities Test: Manual.
        Western Psychological Services, Los Angeles, CA1982
        • Tommasin S.
        • De Luca F.
        • Ferrante I.
        • et al.
        Cognitive fatigability as a quantifiable distinct phenomenon in multiple sclerosis.
        J. Neuropsychol. 2019; ([Epub ahead of print])
        • Trojano M.
        • Liguori M.
        • Zimatore G.
        • et al.
        Age-related disability in multiple sclerosis.
        Ann. Neurol. 2002; 51: 475-480
        • Van Geel F.
        • Moumdjian L.
        • Lamers I.
        • et al.
        Measuring walking-related performance fatigability in clinical practice: a systematic review.
        Eur. J. Phys. Rehabil. Med. 2019; ([Epub ahead of print])
        • Walker L.A.
        • Berard J.A.
        • Berrigan L.I.
        • et al.
        Detecting cognitive fatigue in multiple sclerosis: method matters.
        J. Neurol. Sci. 2012; 316: 86-92
        • Walker L.A.S.
        • Lindsay-Brown A.P.
        • Berard J.A
        Cognitive fatigability interventions in neurological conditions: a systematic review.
        Neurol. Ther. 2019; 8: 251-271
        • Wallin M.T.
        • Culpepper W.J.
        • et al.
        The prevalence of MS in the United States: a population-based estimate using health claims data.
        Neurology. 2019; 92: 1029-1040
        • Yildiz M.
        The impact of slower walking speed on activities of daily living in patients with multiple sclerosis.
        Int. J. Clin. Pract. 2012; 66: 1088-1094