Journal of Neurology

, Volume 264, Issue 1, pp 32–39 | Cite as

Exercise effects in Huntington disease

  • Sebastian Frese
  • Jens A. Petersen
  • Maria Ligon-Auer
  • Sandro Manuel Mueller
  • Violeta Mihaylova
  • Saskia M. Gehrig
  • Veronika Kana
  • Elisabeth J. Rushing
  • Evelyn Unterburger
  • Georg Kägi
  • Jean-Marc Burgunder
  • Marco Toigo
  • Hans H. Jung
Original Communication

Abstract

Huntington disease (HD) is a relentlessly progressive neurodegenerative disorder with symptoms across a wide range of neurological domains, including cognitive and motor dysfunction. There is still no causative treatment for HD but environmental factors such as passive lifestyle may modulate disease onset and progression. In humans, multidisciplinary rehabilitation has a positive impact on cognitive functions. However, a specific role for exercise as a component of an environmental enrichment effect has been difficult to demonstrate. We aimed at investigating whether endurance training (ET) stabilizes the progression of motor and cognitive dysfunction and ameliorates cardiovascular function in HD patients. Twelve male HD patients (mean ± SD, 54.8 ± 7.1 years) and twelve male controls (49.1 ± 6.8 years) completed 26 weeks of endurance training. Before and after the training intervention, clinical assessments, exercise physiological tests, and a body composition measurement were conducted and a muscle biopsy was taken from M. vastus lateralis. To examine the natural course of the disease, HD patients were additionally assessed 6 months prior to ET. During the ET period, there was a motor deficit stabilization as indicated by the Unified Huntington’s Disease Rating Scale motor section score in HD patients (baseline: 18.6 ± 9.2, pre-training: 26.0 ± 13.7, post-training: 26.8 ± 16.4). Peak oxygen uptake (\(\dot{V}{\text{O}}_{{ 2 {\text{peak}}}}\)) significantly increased in HD patients (∆\(\dot{V}{\text{O}}_{{ 2 {\text{peak}}}}\) = +0.33 ± 0.28 l) and controls (∆\(\dot{V}{\text{O}}_{{ 2 {\text{peak}}}}\) = +0.29 ± 0.41 l). No adverse effects of the training intervention were reported. Our results confirm that HD patients are amenable to a specific exercise-induced therapeutic strategy indicated by an increased cardiovascular function and a stabilization of motor function.

Keywords

Unified Huntington disease rating scale (UHDRS) Endurance training Motor function Cardiovascular function Peak oxygen uptake (\(\dot{V}{\text{O}}_{{ 2 {\text{peak}}}}\)

Notes

Acknowledgments

We thank Dr. Niels Hagenbuch and Prof. Burkhardt Seifert of the Epidemiology, Biostatistics and Prevention Institute (University of Zurich) for their support and assistance during the statistical analyses. The study was supported by the Swiss National Science Foundation (320030_135539) and the Jacques and Gloria Gossweiler Foundation.

Compliance with ethical standards

Conflicts of interest

None. The results of this study do not constitute endorsement by ACSM. The authors declare that the results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation.

Ethical standards

All patients and controls gave their written informed consent. The protocol was approved by the ethics committee of the Canton of Zurich (KEK-ZH-Nr. 2009-0119) and was in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki for research involving human subjects (ClinicalTrials.gov NCT01879267)

Funding

The study was supported by the Swiss National Science Foundation (320030_135539) and the Jacques and Gloria Gossweiler Foundation. The funding sources had no role in writing of the manuscript or in the decision to submit it for publication.

References

  1. 1.
    Baker LD, Frank LL, Foster-Schubert K et al (2010) Effects of aerobic exercise on mild cognitive impairment: a controlled trial. Arch Neurol 67:71–79PubMedPubMedCentralGoogle Scholar
  2. 2.
    Benedict RHB, Schretlen D, Groninger L, Brandt J (1998) Hopkins verbal learning test revised: normative data and analysis of inter-form and test-retest reliability. Clin Neuropsychol 12:43–55CrossRefGoogle Scholar
  3. 3.
    Bohlen S, Ekwall C, Hellstrom K et al (2013) Physical therapy in Huntington’s disease—toward objective assessments? Eur J Neurol 20:389–393CrossRefPubMedGoogle Scholar
  4. 4.
    Borg E, Kaijser L (2006) A comparison between three rating scales for perceived exertion and two different work tests. Scand J Med Sci Sports 16:57–69CrossRefPubMedGoogle Scholar
  5. 5.
    Busse M, Khalil H, Brooks S, Quinn L, Rosser A (2012) Practice, progress and future directions for physical therapies in huntingtons disease. J Huntingt Dis 1:175–185Google Scholar
  6. 6.
    Busse M, Quinn L, Debono K et al (2013) A randomized feasibility study of a 12-week community-based exercise program for people with Huntington’s disease. J Neurol Phys Ther 37:149–158CrossRefPubMedGoogle Scholar
  7. 7.
    Butters N, Granholm E, Salmon DP, Grant I, Wolfe J (1987) Episodic and semantic memory: a comparison of amnesic and demented patients. J Clin Exp Neuropsychol 9:479–497CrossRefPubMedGoogle Scholar
  8. 8.
    Butters N, Wolfe J, Granholm E, Martone M (1986) An assessment of verbal recall, recognition and fluency abilities in patients with Huntington’s disease. Cortex 22:11–32CrossRefPubMedGoogle Scholar
  9. 9.
    Cruickshank TM, Thompson JA, Dominguez DJ et al (2015) The effect of multidisciplinary rehabilitation on brain structure and cognition in Huntington’s disease: an exploratory study. Brain Behav 5:e00312CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    van Dellen A, Cordery PM, Spires TL, Blakemore C, Hannan AJ (2008) Wheel running from a juvenile age delays onset of specific motor deficits but does not alter protein aggregate density in a mouse model of Huntington’s disease. BMC Neurosci 9:34CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Goodwin VA, Richards SH, Taylor RS, Taylor AH, Campbell JL (2008) The effectiveness of exercise interventions for people with Parkinson’s disease: a systematic review and meta-analysis. Mov Disord 23:631–640CrossRefPubMedGoogle Scholar
  12. 12.
    Harrison DJ, Busse M, Openshaw R, Rosser AE, Dunnett SB, Brooks SP (2013) Exercise attenuates neuropathology and has greater benefit on cognitive than motor deficits in the R6/1 Huntington’s disease mouse model. Exp Neurol 248:457–469CrossRefPubMedGoogle Scholar
  13. 13.
    Helgerud J, Hoydal K, Wang E et al (2007) Aerobic high-intensity intervals improve VO2max more than moderate training. Med Sci Sports Exerc 39:665–671CrossRefPubMedGoogle Scholar
  14. 14.
    Hodges JR, Salmon DP, Butters N (1990) Differential impairment of semantic and episodic memory in Alzheimer’s and Huntington’s diseases: a controlled prospective study. J Neurol Neurosurg Psychiatry 53:1089–1095CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Huntington Study Group (1996) Unified Huntington’s Disease Rating Scale: reliability and consistency. Mov Disord 11:136–142CrossRefGoogle Scholar
  16. 16.
    Item F, Nocito A, Thony S et al (2013) Combined whole-body vibration, resistance exercise, and sustained vascular occlusion increases PGC-1alpha and VEGF mRNA abundances. Eur J Appl Physiol 113:1081–1090CrossRefPubMedGoogle Scholar
  17. 17.
    Kosinski CM, Schlangen C, Gellerich FN et al (2007) Myopathy as a first symptom of Huntington’s disease in a Marathon runner. Mov Disord 22(11):1637–1640. doi: 10.1002/mds.21550 CrossRefPubMedGoogle Scholar
  18. 18.
    Lemiere J, Decruyenaere M, Evers-Kiebooms G, Vandenbusche E, Dom R (2004) Cognitive changes in patients with Huntington’s disease (HD) and asymptomatic carriers of the HD mutation–a longitudinal follow-up study. J Neurol 251:935–942CrossRefPubMedGoogle Scholar
  19. 19.
    Mattis S (1988) Dementia Rating Scale: professional manual. Psychological Assessment Resources Inc, OdessaGoogle Scholar
  20. 20.
    Mattis S (1976) Mental status examination for organic mental syndrome in the elderly patient. In: Bellack L, Karasu T (ed) Geriatrics psychiatry: a handbook for psychiatrists and primary care physicians. New York, pp 77–121Google Scholar
  21. 21.
    Pang TY, Stam NC, Nithianantharajah J, Howard ML, Hannan AJ (2006) Differential effects of voluntary physical exercise on behavioral and brain-derived neurotrophic factor expression deficits in Huntington’s disease transgenic mice. Neurosci 141:569–584CrossRefGoogle Scholar
  22. 22.
    Potter MC, Yuan C, Ottenritter C, Mughal M, van Praag H (2010) Exercise is not beneficial and may accelerate symptom onset in a mouse model of Huntington’s disease. PLoS Curr 2:RRN1201CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Reitan R (1958) Validity of the trail making test as an indicator of organic brain damage. Percept Mot Skills 8:271–276CrossRefGoogle Scholar
  24. 24.
    Russell AP, Feilchenfeldt J, Schreiber S et al (2003) Endurance training in humans leads to fiber type-specific increases in levels of peroxisome proliferator-activated receptor-gamma coactivator-1 and peroxisome proliferator-activated receptor-alpha in skeletal muscle. Diabetes 52:2481–2874CrossRefGoogle Scholar
  25. 25.
    Salmon DP, Kwo-on-Yuen PF, Heindel WC, Butters N, Thal LJ (1989) Differentiation of Alzheimer’s disease and Huntington’s disease with the Dementia Rating Scale. Arch Neurol 46:1204–1208CrossRefPubMedGoogle Scholar
  26. 26.
    Smith A (1973) Symbol digit modalities test manual. Western Psychological Services, Los AngelesGoogle Scholar
  27. 27.
    Stroop J (1935) Studies of interference in serial verbal reactions. J Exp Psychol 18:643–662CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Sebastian Frese
    • 1
    • 2
  • Jens A. Petersen
    • 1
  • Maria Ligon-Auer
    • 1
  • Sandro Manuel Mueller
    • 1
    • 2
  • Violeta Mihaylova
    • 1
  • Saskia M. Gehrig
    • 1
    • 2
  • Veronika Kana
    • 3
  • Elisabeth J. Rushing
    • 3
  • Evelyn Unterburger
    • 1
  • Georg Kägi
    • 4
  • Jean-Marc Burgunder
    • 5
  • Marco Toigo
    • 2
    • 6
  • Hans H. Jung
    • 1
  1. 1.Department of NeurologyUniversity Hospital and University of ZurichZurichSwitzerland
  2. 2.Institute of Human Movement Sciences and SportETH ZurichZurichSwitzerland
  3. 3.Institute of NeuropathologyUniversity Hospital and University of ZurichZurichSwitzerland
  4. 4.Department of NeurologyCantonal Hospital St. GallenSt. GallenSwitzerland
  5. 5.Department of Neurology and Swiss Huntington Disease CentreUniversity of BernBernSwitzerland
  6. 6.Balgrist University Hospital, Department of OrthopedicsUniversity of ZurichZurichSwitzerland

Personalised recommendations