Improved Physical Fitness Correlates With Improved Cognition in Multiple Sclerosis

Published:March 06, 2014DOI:



      To determine whether there is an association between improvements in objective measures of physical fitness and performance on cognitive tests in people with multiple sclerosis (MS).


      Post hoc correlational analysis in which people demonstrating physical improvement were compared with those not demonstrating physical improvement.


      Individuals with MS residing in the community.


      Adults with clinically confirmed MS (N=88) who participated in a controlled trial of a telephone-based health promotion intervention, chose to work on exercise, and completed the pre- and postintervention assessments.


      Participants were measured for strength (isokinetic dynamometer), aerobic fitness (bicycle ergometer), and cognition (Paced Auditory Serial Addition Test [PASAT], Trail Making Test [TMT]) at baseline and 12 weeks later. Change in fitness was calculated by subtracting each participant's baseline score from the outcome score, and then transforming the difference to a z score. Individuals with a z score ≥1 on any fitness measure were placed in the physically improved group (n=25). All others were in the physically not improved group (n=57).

      Main Outcome Measures

      TMT, PASAT.


      After controlling for covariates (age, sex, ethnicity, education, disease activity, MS type), there was a significant group-by-time interaction, suggesting that cognitive functioning changed over time based on level of fitness. Participants in the physically improved group demonstrated improved performance on measures of executive functioning after 12 weeks of exercise.


      The results of this study lend support to the hypothesis that change in fitness is associated with improved executive functioning in people with MS.


      List of abbreviations:

      MS (multiple sclerosis), PASAT (Paced Auditory Serial Addition Test), rpm (revolutions per minute), TMT-A (Trail Making Test–Part A), TMT-B (Trail Making Test–Part B), TMT-BA (Trail Making Test–Part B minus Part A)
      To read this article in full you will need to make a payment


      Subscribe to Archives of Physical Medicine and Rehabilitation
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Benedict R.H.
        • Cookfair D.
        • Gavett R.
        • et al.
        Validity of the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS).
        J Int Neuropsychol Soc. 2006; 12: 549-558
        • Patti F.
        • Amato M.P.
        • Trojano M.
        • et al.
        Cognitive impairment and its relation with disease measures in mildly disabled patients with relapsing-remitting multiple sclerosis: baseline results from the Cognitive Impairment in Multiple Sclerosis (COGIMUS) study.
        Mult Scler. 2009; 15: 779-788
        • Rao S.M.
        • Leo G.J.
        • Bernardin L.
        • Unverzagt F.
        Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction.
        Neurology. 1991; 41: 685-691
        • O'Connor P.
        • Lee L.
        • Ng P.T.
        • Narayana P.
        • Wolinsky J.S.
        Determinants of overall quality of life in secondary progressive MS: a longitudinal study.
        Neurology. 2001; 57: 889-891
        • O'Connor R.J.
        • Cano S.J.
        • Ramió i Torrentà L.
        • Thompson A.J.
        • Playford E.D.
        Factors influencing work retention for people with multiple sclerosis: cross-sectional studies using qualitative and quantitative methods.
        J Neurol. 2005; 252: 892-896
        • Demaree H.A.
        • DeLuca J.
        • Gaudino E.A.
        • Diamond B.J.
        Speed of information processing as a key deficit in multiple sclerosis: implications for rehabilitation.
        J Neurol Neurosurg Psychiatry. 1999; 67: 661-663
        • Schultheis M.T.
        • Garay E.
        • DeLuca J.
        The influence of cognitive impairment on driving performance in multiple sclerosis.
        Neurology. 2001; 56: 1089-1094
        • Beatty W.W.
        • Paul R.H.
        • Blanco C.R.
        • Hames K.A.
        • Wilbanks S.L.
        Attention in multiple sclerosis: correlates of impairment on the WAIS-R Digit Span Test.
        Appl Neuropsychol. 1995; 2: 139-144
        • Benedict R.H.
        • Zivadinov R.
        • Carone D.A.
        • et al.
        Regional lobar atrophy predicts memory impairment in multiple sclerosis.
        AJNR Am J Neuroradiol. 2005; 26: 1824-1831
        • Langdon D.W.
        • Thompson A.J.
        Multiple sclerosis: a preliminary study of selected variables affecting rehabilitation outcome.
        Mult Scler. 1999; 5: 94-100
        • Krupp L.B.
        • Christodoulou C.
        • Melville P.
        • et al.
        Multicenter randomized clinical trial of donepezil for memory impairment in multiple sclerosis.
        Neurology. 2011; 76: 1500-1507
        • Morrow S.A.
        • Kaushik T.
        • Zarevics P.
        • et al.
        The effects of L-amphetamine sulfate on cognition in MS patients: results of a randomized controlled trial.
        J Neurol. 2009; 256: 1095-1102
        • Bever Jr., C.T.
        • Anderson P.A.
        • Leslie J.
        • et al.
        Treatment with oral 3,4 diaminopyridine improves leg strength in multiple sclerosis patients: results of a randomized, double-blind, placebo-controlled, crossover trial.
        Neurology. 1996; 47: 1457-1462
        • Rossini P.M.
        • Pasqualetti P.
        • Pozzilli C.
        • et al.
        Fatigue in progressive multiple sclerosis: results of a randomized, double-blind, placebo-controlled, crossover trial of oral 4-aminopyridine.
        Mult Scler. 2001; 7: 354-358
        • Lovera J.F.
        • Kim E.
        • Heriza E.
        • et al.
        Ginkgo biloba does not improve cognitive function in MS: a randomized placebo-controlled trial.
        Neurology. 2012; 79: 1278-1284
        • Lovera J.F.
        • Frohman E.
        • Brown T.R.
        • et al.
        Memantine for cognitive impairment in multiple sclerosis: a randomized placebo-controlled trial.
        Mult Scler. 2010; 16: 715-723
        • Goverover Y.
        • Arango-Lasprilla J.C.
        • Hillary F.G.
        • Chiaravalloti N.
        • Deluca J.
        Application of the spacing effect to improve learning and memory for functional tasks in traumatic brain injury: a pilot study.
        Am J Occup Ther. 2009; 63: 543-548
        • Goverover Y.
        • Hillary F.G.
        • Chiaravalloti N.
        • Arango-Lasprilla J.C.
        • DeLuca J.
        A functional application of the spacing effect to improve learning and memory in persons with multiple sclerosis.
        J Clin Exp Neuropsychol. 2009; 31: 513-522
        • O'Brien A.R.
        • Chiaravalloti N.
        • Goverover Y.
        • Deluca J.
        Evidenced-based cognitive rehabilitation for persons with multiple sclerosis: a review of the literature.
        Arch Phys Med Rehabil. 2008; 89: 761-769
        • Motl R.W.
        • Sandroff B.M.
        • Benedict R.H.
        Cognitive dysfunction and multiple sclerosis: developing a rationale for considering the efficacy of exercise training.
        Mult Scler. 2011; 17: 1034-1040
        • Angevaren M.
        • Aufdemkampe G.
        • Verhaar H.J.
        • Aleman A.
        • Vanhees L.
        Physical activity and enhanced fitness to improve cognitive function in older people without known cognitive impairment.
        Cochrane Database Syst Rev. 2008; : CD005381
        • Colcombe S.
        • Kramer A.F.
        Fitness effects on the cognitive function of older adults: a meta-analytic study.
        Psychol Sci. 2003; 14: 125-130
        • Kramer A.F.
        • Erickson K.I.
        Capitalizing on cortical plasticity: influence of physical activity on cognition and brain function.
        Trends Cogn Sci. 2007; 11: 342-348
        • Kramer A.F.
        • Erickson K.I.
        • Colcombe S.J.
        Exercise, cognition, and the aging brain.
        J Appl Physiol. 2006; 101: 1237-1242
        • Smith P.J.
        • Blumenthal J.A.
        • Hoffman B.M.
        • et al.
        Aerobic exercise and neurocognitive performance: a meta-analytic review of randomized controlled trials.
        Psychosom Med. 2010; 72: 239-252
        • Colcombe S.J.
        • Kramer A.F.
        • Erickson K.I.
        • et al.
        Cardiovascular fitness, cortical plasticity, and aging.
        Proc Natl Acad Sci U S A. 2004; 101: 3316-3321
        • Hillman C.H.
        • Motl R.W.
        • Pontifex M.B.
        • et al.
        Physical activity and cognitive function in a cross-section of younger and older community-dwelling individuals.
        Health Psychol. 2006; 25: 678-687
        • Caspersen C.J.
        • Powell K.E.
        • Christenson G.M.
        Physical activity, exercise, and physical fitness: definitions and distinctions for health-related research.
        Public Health Rep. 1985; 100: 126-131
        • Prakash R.S.
        • Snook E.M.
        • Erickson K.I.
        • et al.
        Cardiorespiratory fitness: a predictor of cortical plasticity in multiple sclerosis.
        Neuroimage. 2007; 34: 1238-1244
        • Sandroff B.M.
        • Motl R.W.
        Comparison of ActiGraph activity monitors in persons with multiple sclerosis and controls.
        Disabil Rehabil. 2013; 35: 725-731
        • Prakash R.S.
        • Snook E.M.
        • Motl R.W.
        • Kramer A.F.
        Aerobic fitness is associated with gray matter volume and white matter integrity in multiple sclerosis.
        Brain Res. 2010; 1341: 41-51
        • Oken B.S.
        • Kishiyama S.
        • Zajdel D.
        • et al.
        Randomized controlled trial of yoga and exercise in multiple sclerosis.
        Neurology. 2004; 62: 2058-2064
        • Romberg A.
        • Virtanen A.
        • Ruutiainen J.
        • et al.
        Effects of a 6-month exercise program on patients with multiple sclerosis: a randomized study.
        Neurology. 2004; 63: 2034-2038
        • Bombardier C.H.
        • Cunniffe M.
        • Wadhwani R.
        • Gibbons L.E.
        • Blake K.D.
        • Kraft G.H.
        The efficacy of telephone counseling for health promotion in people with multiple sclerosis: a randomized controlled trial.
        Arch Phys Med Rehabil. 2008; 89: 1849-1856
        • Kurtzke J.F.
        Rating neurologic impairment in multiple sclerosis: an Expanded Disability Status Scale (EDSS).
        Neurology. 1983; 33: 1444-1452
        • Spitzer R.L.
        • Williams J.B.
        • Kroenke K.
        • et al.
        Utility of a new procedure for diagnosing mental disorders in primary care. The PRIME-MD 1000 study.
        JAMA. 1994; 272: 1749-1756
        • Bowen J.
        • Gibbons L.
        • Gianas A.
        • Kraft G.H.
        Self-administered Expanded Disability Status Scale with functional system scores correlates well with a physician-administered test.
        Mult Scler. 2001; 7: 201-206
        • Kaufman M.
        • Moyer D.
        • Norton J.
        The significant change for the Timed 25-Foot Walk in the multiple sclerosis functional composite.
        Mult Scler. 2000; 6: 286-290
        • Gronwall D.M.
        Paced Auditory Serial-Addition Task: a measure of recovery from concussion.
        Percept Mot Skills. 1977; 44: 367-373
        • Strauss E.
        • Sherman E.
        • Spreen O.
        A compendium of neuropsychological tests: administration, norms, and commentary.
        3rd ed. Oxford Univ Pr, New York2006
        • Sanchez-Cubillo I.
        • Perianez J.A.
        • Adrover-Roig D.
        • et al.
        Construct validity of the Trail Making Test: role of task-switching, working memory, inhibition/interference control, and visuomotor abilities.
        J Int Neuropsychol Soc. 2009; 15: 438-450
        • Debette S.
        • Seshadri S.
        • Beiser A.
        • et al.
        Midlife vascular risk factor exposure accelerates structural brain aging and cognitive decline.
        Neurology. 2011; 77: 461-468
        • Zachary R.A.
        • Gorsuch R.L.
        Continuous norming: implications for the WAIS-R.
        J Clin Psychol. 1985; 41: 86-94
        • Crawford J.R.
        • Stewart L.E.
        • Cochrane R.H.
        • Foulds J.A.
        • Besson J.A.
        • Parker D.M.
        Estimating premorbid IQ from demographic variables: regression equations derived from a UK sample.
        Br J Clin Psychol. 1989; 28: 275-278
        • Parmenter B.A.
        • Testa S.M.
        • Schretlen D.J.
        • Weinstock-Guttman B.
        • Benedict R.H.
        The utility of regression-based norms in interpreting the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS).
        J Int Neuropsychol Soc. 2010; 16: 6-16
        • Leckliter I.N.
        • Matarazzo J.D.
        The influence of age, education, IQ, gender, and alcohol abuse on Halstead-Reitan Neuropsychological Test Battery performance.
        J Clin Psychol. 1989; 45: 484-512
        • Erdfelder E.
        • Faul F.
        • Buchner A.
        GPOWER: a general power analysis program.
        Behav Res Methods Instrum Comput. 2013; 28: 1-11
        • Cohen J.
        Statistical power analysis for the behavioral sciences.
        2nd ed. Hillsdale: Erlbaum, 1988
        • Bombardier C.H.
        • Ehde D.M.
        • Gibbons L.E.
        • et al.
        Telephone-based physical activity counseling for major depression in people with multiple sclerosis.
        J Consult Clin Psychol. 2013; 81: 89-99
        • Chiaravalloti N.D.
        • DeLuca J.
        Cognitive impairment in multiple sclerosis.
        Lancet Neurol. 2008; 7: 1139-1151
        • Motl R.W.
        • Fernhall B.
        Accurate prediction of cardiorespiratory fitness using cycle ergometry in minimally disabled persons with relapsing-remitting multiple sclerosis.
        Arch Phys Med Rehabil. 2012; 93: 490-495
        • Benedict R.H.
        • Fischer J.S.
        • Archibald C.J.
        • et al.
        Minimal neuropsychological assessment of MS patients: a consensus approach.
        Clin Neuropsychol. 2002; 16: 381-397
        • Crowe S.F.
        The differential contribution of mental tracking, cognitive flexibility, visual search, and motor speed to performance on parts A and B of the Trail Making Test.
        J Clin Psychol. 1998; 5: 585-591
        • Bever Jr., C.T.
        • Grattan L.
        • Panitch H.S.
        • Johnson K.P.
        The Brief Repeatable Battery of Neuropsychological Tests for Multiple Sclerosis: a preliminary serial study.
        Mult Scler. 1995; 1: 165-169