The importance of physical activity to preserve hippocampal volume in people with multiple sclerosis: a structural MRI study

Abstract

Background

There is scarce data as to the association between physical activity and the volumes of subcortical brain regions in people with multiple sclerosis (PwMS).

Objective

To compare the volumetric measures of subcortical brain structures in physically active and insufficiently active PwMS.

Methods

This cross‐sectional study comprised 153 PwMS (39.3 ± 12.0 years, 68.0% female) who had undergone a complete neurological examination, computerized cognitive evaluation and brain MRI (using a high‐resolution scanner). MRI volumetric analysis was based on the FreeSurfer image analysis suite. Regions of interest included the hippocampus, amygdala, brain stem, basal ganglia, thalamus, accumbens nucleus, putamen, caudate and pallidum. Two MRI metrics, total volume (mm3) and estimated percentile of the subcortical region according to adjusted normative population, were calculated for each individual and brain region. Based on scores obtained from the Godin Leisure-Time Exercise Questionnaire, the cohort was subsequently divided into two groups, physically active (n = 77) and insufficiently active (n = 76).

Results

The left hippocampus estimated percentile point significantly differentiated between active and insufficiently active PwMS (48.5 (S.D. = 32.2) vs. 36.4 (S.D. = 29.8); p = 0.004), even after controlling for disability (p = 0.011) and cognition (p = 0.021). The right hippocampal estimated percentile point was also significantly different between groups (46.7 (S.D. = 30.6) vs. 34.6 (S.D. = 30.8); p = 0.004). Subcortical volume of the right hippocampus explained 19.4% of the variance between the groups (p = 0.008), even after controlling for disability (p = 0.013) and cognition (p = 0.020).

Conclusions

Our results provide evidence that PwMS who regularly participate in leisure-time physical activities maintain their hippocampal volume, regardless of their disability and cognitive capabilities.

This is a preview of subscription content, access via your institution.

References

  1. 1.

    Krieger SC, Cook K, De Nino S, Fletcher M (2016) The topographical model of multiple sclerosis: A dynamic visualization of disease course. Neurol Neuroimmunol Neuroinflamm 3:e279. https://doi.org/10.1212/nxi.0000000000000279

    Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Compston A, Coles A (2008) Multiple sclerosis. Lancet 372:1502–1517. https://doi.org/10.1016/s0140-6736(08)61620-7

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Motl RW, Sandroff BM, Kwakkel G, Dalgas U, Feinstein A, Heesen C, Feys P, Thompson AJ (2017) Exercise in patients with multiple sclerosis. Lancet Neurol 16:848–856. https://doi.org/10.1016/s1474-4422(17)30281-8

    Article  PubMed  Google Scholar 

  4. 4.

    Motl RW, Sandroff BM (2015) Benefits of exercise training in multiple sclerosis. Curr Neurol Neurosci Rep 15:62. https://doi.org/10.1007/s11910-015-0585-6

    Article  PubMed  Google Scholar 

  5. 5.

    Dalgas U, Langeskov-Christensen M, Stenager E, Riemenschneider M, Hvid LG (2019) Exercise as medicine in multiple sclerosis-time for a paradigm shift: preventive, symptomatic, and disease-modifying aspects and perspectives. Curr Neurol Neurosci Rep 19:88. https://doi.org/10.1007/s11910-019-1002-3

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Firth J, Stubbs B, Vancampfort D, Schuch F, Lagopoulos Rosenbaum S, Ward PB (2018) Effect of aerobic exercise on hippocampal volume in humans: a systematic review and meta-analysis. Neuroimage 166:230–238. https://doi.org/10.1016/j.neuroimage.2017.11.007

    Article  PubMed  Google Scholar 

  7. 7.

    Halloway S, Arfanakis K, Wilbur J, Schoeny ME, Pressler SJ (2019) Accelerometer physical activity is associated with greater gray matter volumes in older adults without dementia or mild cognitive impairment. J Gerontol B Psychol Sci Soc Sci 74:1142–1151. https://doi.org/10.1093/geronb/gby010

    Article  PubMed  Google Scholar 

  8. 8.

    Klaren RE, Hubbard EA, Motl RW, Pilutti LA, Wetter NC, Sutton BP (2015) Objectively measured physical activity is associated with brain volumetric measurements in multiple sclerosis. Behav Neurol 2015:48253666. https://doi.org/10.1155/2015/482536

    Article  Google Scholar 

  9. 9.

    Motl RW, Pilutti LA, Hubbard E, Wetter NC, Sosnoff JJ, Suttom BP (2015) Cardiorespiratory fitness and its association with thalamic, hippocampal, and basal ganglia volumes in multiple sclerosis. Neuroimage Clin 7:661–666. https://doi.org/10.1016/j.nicl.2015.02.017

    Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Leavitt VM, Cirnigliaro C, Cohen A, Farag A, Brooks M, Wecht JM, Wylie GR, Chiaravalloti ND, DeLuca J, Sumowski JF (2014) Aerobic exercise increases hippocampal volume and improves memory in multiple sclerosis: preliminary findings. Neurocase 20:695–697. https://doi.org/10.1080/13554794.2013.841951

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Sandroff BM, Johnson CL, Motl RW (2017) Exercise training effects on memory and hippocampal viscoelasticity in multiple sclerosis: a novel application of magnetic resonance elastography. Neuroradiology 59:61–67. https://doi.org/10.1007/s00234-016-1767-x

    Article  PubMed  Google Scholar 

  12. 12.

    Kjølhede T, Siemonsen S, Wenzel D, Stellmann J-P, Ringgaard S, Pedersen BG, Stenager E, Petersen T, Vissing K, Heesen C, Dalgas U (2018) Can resistance training impact MRI outcomes in relapsing-remitting multiple sclerosis? Mult Scler 24:1356–1365. https://doi.org/10.1177/1352458517722645

    Article  PubMed  Google Scholar 

  13. 13.

    Menascu S, Stern M, Aloni R, Kalron A, Magalshvili D, Achiron A (2019) Assessing cognitive performance in radiologically isolated syndrome. Mult Scler Relat Disord 32:70–73. https://doi.org/10.1016/j.msard.2019.04.030

    Article  PubMed  Google Scholar 

  14. 14.

    Rocca MA, Battaglini M, Benedict RH, Stefano De, Geurts JJG, Henry RG, Horsfield MA, Jenkinson M, Pagani E, Filippi M (2017) Brain MRI atrophy quantification in MS: from methods to clinical application. Neurology 88:403–413. https://doi.org/10.1212/wnl.0000000000003542

    Article  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Kalinin I, Makshakov G, Evdoshenko E (2020) The impact of intracortical lesions on volumes of subcortical structures in multiple sclerosis. AJNR Am J Neuroradiol 41:804–808. https://doi.org/10.3174/ajnr.a6513

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Pfefferbaum A, Rohlfing T, Rosenbloom MJ, Sullivan EV (2012) Combining atlas-based parcellation of regional brain data acquired across scanners at 1.5 T and 3.0 T field strengths. Neuroimage 60:940–951. https://doi.org/10.1016/j.neuroimage.2012.01.092

    Article  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Polman CH, Reingold SC, Banwell B et al (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69:292–302. https://doi.org/10.1002/ana.22366

    Article  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33:1444–1452. https://doi.org/10.1212/wnl.33.11.1444

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Achiron A, Chapman J, Magalashvili D et al (2013) Modeling of cognitive impairment by disease duration in multiple sclerosis: a cross-sectional study. PLoS ONE 8(8):e71058. https://doi.org/10.1371/journal.pone.0071058

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Fischl B, Salat DH, Busa E et al (2002) Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron 33:341–355. https://doi.org/10.1016/s0896-6273(02)00569-x

    CAS  Article  Google Scholar 

  21. 21.

    Fischl B, Salat DH, van der Kouwe AJ, Makris N, Segonne F, Quinn BT, Dale AMI (2004) Sequence- independent segmentation of magnetic resonance images. Neuroimage 23:S69–S84. https://doi.org/10.1016/j.neuroimage.2004.07.016

    Article  PubMed  Google Scholar 

  22. 22.

    Rosas HD, Liu AK, Hersch S, Glessner M, Ferrante RJ, Salat DH, van der Kouwe A, Jenkins BG, Dale AM, Fischl B (2004) Regional and progressive thinning of the cortical ribbon in Huntington’s disease. Neurology 58:695–701. https://doi.org/10.1212/wnl.58.5.695

    Article  Google Scholar 

  23. 23.

    Kuperberg GR, Broome MR, McGuire PK et al (2003) Regionally localized thinning of the cerebral cortex in schizophrenia. Arch Gen Psychiatry 60:878–888. https://doi.org/10.1001/archpsyc.60.9.878

    Article  PubMed  Google Scholar 

  24. 24.

    Salat DH, Buckner RL, Snyder AZ, Greve DN, Desikan RSR, Busa E, Morris JC, Dae AM, Fischl B (2004) Thinning of the cerebral cortex in aging. Cereb Cortex 14:721–730. https://doi.org/10.1093/cercor/bhh032

    Article  PubMed  Google Scholar 

  25. 25.

    Han X, Jovicich J, Salat D et al (2006) Reliability of MRI-derived measurements of human cerebral cortical thickness: the effects of field strength, scanner upgrade and manufacturer. Neuroimage 32:180–194. https://doi.org/10.1016/j.neuroimage.2006.02.051

    Article  PubMed  Google Scholar 

  26. 26.

    Sandroff BM, Motl RW, Bamman M, Cutter GR, Bolding M, Rinker JR, Wylie GR, Genova H, Deuca J (2018) Rationale and design of a single-blind, randomised controlled trial of exercise training for managing learning and memory impairment in persons with multiple sclerosis. BMJ Open 8:023231. https://doi.org/10.1136/bmjopen-2018-023231

    Article  Google Scholar 

  27. 27.

    Huiskamp M, Moumdjian L, van Asch P et al (2019) A pilot study of the effects of running training on visuospatial memory in MS: a stronger functional embedding of the hippocampus in the default-mode network? Mult Scler. https://doi.org/10.1177/1352458519863644

    Article  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Dalgas U (2017) Exercise therapy in multiple sclerosis and its effects on function and the brain. Neurodegener Dis Manag 7:35–40. https://doi.org/10.2217/nmt-2017-0040

    Article  PubMed  Google Scholar 

  29. 29.

    Potvin O, Mouiha A, Dieumegarde L, Duchesne S (2016) Alzheimer׳s disease neuroimaging initiative. FreeSurfer subcortical normative data. Data Brief 9:732–736. https://doi.org/10.1016/j.dib.2016.10.001

    Article  PubMed  PubMed Central  Google Scholar 

  30. 30.

    Potvin O, Mouiha A, Dieumegarde L, Duchesne S, Alzheimer’s Disease Neuroimaging (2016) Initiative Normative data for subcortical regional volumes over the lifetime of the adult human brain. Neuroimage 137:9–20. https://doi.org/10.1016/j.neuroimage.2016.05.016

    Article  PubMed  Google Scholar 

  31. 31.

    Crawford JR, Garthwaite PH (2006) Comparing patients’ predicted test scores from a regression equation with their obtained scores: a significance test and point estimate of abnormality with accompanying confidence limits. Neuropsychology 20(3):259–271. https://doi.org/10.1037/0894-4105.20.3.259

    Article  PubMed  Google Scholar 

  32. 32.

    Godin G, Shephard RJ (1985) A simple method to assess exercise behavior in the community. Can J Appl Sport Sci 10:141–146

    CAS  PubMed  Google Scholar 

  33. 33.

    Sikes EM, Richardson EV, Cederberg KJ, Sasaki JE, Sandroff BM, Motl RW (2019) Use of the godin leisure-time exercise questionnaire in multiple sclerosis research: a comprehensive narrative review. Disabil Rehabil 41:1243–1267. https://doi.org/10.1080/09638288.2018.1424956

    Article  PubMed  Google Scholar 

  34. 34.

    Prakash RS, Patterson B, Janssen A, Abduljalil A, Boster A (2011) Physical activity associated with increased resting-state functional connectivity in multiple sclerosis. J Int Neuropsychol Soc 17:986–997. https://doi.org/10.1017/s1355617711001093

    Article  PubMed  Google Scholar 

  35. 35.

    Voss MW, Nagamatsu LS, Liu-Ambrose T, Kramer AF (1985) Exercise, brain, and cognition across the life span. J Appl Physiol 111:1505–1513. https://doi.org/10.1152/japplphysiol.00210.2011

    Article  Google Scholar 

  36. 36.

    Erickson KI, Voss MW, Prakash RS et al (2011) Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci USA 108:3017–3022. https://doi.org/10.1073/pnas.1015950108

    Article  PubMed  Google Scholar 

  37. 37.

    Szuhany KL, Bugatti M, Otto MW (2015) A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor. J Psychiatr Res 60:56–64. https://doi.org/10.1016/j.jpsychires.2014.10.003

    Article  PubMed  Google Scholar 

  38. 38.

    White LJ, Castellano V (2008) Exercise and brain health–implications for multiple sclerosis: part 1–neuronal growth factors. Sports Med 38:91–100. https://doi.org/10.2165/00007256-200838020-00001

    Article  PubMed  Google Scholar 

  39. 39.

    Sallis JF (2010) Measuring physical activity: practical approaches for program in native American communities. J Public Health Manag Pract 16:404–410. https://doi.org/10.1097/phh.0b013e3181d52804

    Article  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Motl RW, Bollaert RE, Sandroff BM (2018) Validation of the godin leisure-time exercise questionnaire classification coding system using accelerometry in multiple sclerosis. Rehabil Psychol 63:77–82. https://doi.org/10.1037/rep0000162

    Article  PubMed  Google Scholar 

  41. 41.

    Diamond BJ, Johnson SK, Kaufman M, Graves L (2008) Relationships between information processing, depression, fatigue and cognition in multiple sclerosis. Arch Clin Neuropsychol 23(2):189–199. https://doi.org/10.1016/j.acn.2007.10.002

    Article  PubMed  Google Scholar 

Download references

Funding

None.

Author information

Affiliations

Authors

Contributions

AK: conceptualization, formal analysis investigation, writing original draft. SM: data curation, writing—review & editing. CH: validation, writing—review & editing. AA: Writing – review & editing, visualization and supervision

Corresponding author

Correspondence to Alon Kalron.

Ethics declarations

Conflicts of interest

The authors declare that they have no conflict of interest.

Ethics approval

The study was approved by the Sheba Institutional Review Board Ethics Committee (Ethics ref. 5596‐08/141210), in addition to a full exemption from written or verbal consent from the study participants.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Kalron, A., Menascu, S., Hoffmann, C. et al. The importance of physical activity to preserve hippocampal volume in people with multiple sclerosis: a structural MRI study. J Neurol 267, 3723–3730 (2020). https://doi.org/10.1007/s00415-020-10085-1

Download citation

Keywords

  • Multiple sclerosis
  • Hippocampus
  • Physical activity
  • Cognition
  • Structural MRI
  • Brain volume