Effektivität von Sport bei M. Parkinson

I. Reuter; G. Ebersbach

doi:10.1055/s-0032-1308983

Aktuelle Neurologie, Table of Contents

Aktuelle Neurologie 2012; 39(05): 236-247
DOI: 10.1055/s-0032-1308983

Übersicht

Effektivität von Sport bei M. Parkinson

Efficacy of Exercise in Parkinson’s Disease

Authors

I. Reuter

¹Neurologische Klinik, Justus-Liebig Universität, Gießen
G. Ebersbach

²Neurologische Fachklinik für Bewegungsstörungen und Parkinson Beelitz Heilstätten, Neurologie, Beelitz-Heilstätten

Abstract

Zusammenfassung

Es gibt zunehmend Hinweise, dass der durch kognitiven Abbau und pharmakorefraktäre motorische Defizite bestimmte Langzeitverlauf der Parkinson-Erkrankung durch intensives körperliches Training verbessert werden kann. In Tiermodellen der Parkinson-Erkrankung hat körperliche Aktivität möglicherweise durch Freisetzung neurotropher Faktoren mediierte neuroprotektive und neuroplastische Effekte, die sich positiv auf die Motorik auswirken. Zahlreiche klinische Studien sprechen dafür, dass die Behinderung durch pharmakorefraktäre Bewegungseinschränkungen bei der Parkinson-Erkrankung durch aktivierende Therapie reduziert werden kann. Durch kurz- und mittelfristige Trainingsinterventionen (1–6 Monate) konnten positive Effekte auf Gang, Haltung, Gleichgewicht, Muskelkraft und in einigen Studien auch auf Parkinson-spezifische Defizite und die Lebensqualität erreicht werden. Auch Verbesserungen der kognitiven Leistungsfähigkeit durch körperliche Aktivität wurden sowohl im Tiermodell als auch in klinischen Studien nachgewiesen. Eingesetzt wurden Physiotherapie, Wandern, Nordic Walking und Krafttraining. Körperliche Aktivität im mittleren Lebensalter scheint das zukünftige Risiko an M. Parkinson zu erkranken zu mindern. Die neuronalen Mechanismen der aktivierenden Therapie bei IPS und die Auswirkungen auf Progression und Prognose der Erkrankung können vorerst nur spekulativ beurteilt werden. Trotzdem sollten aktivierende Therapien einschließlich der Sporttherapie aufgrund der positiven Ergebnisse von klinischer und Grundlagenforschung schon jetzt einen höheren Stellenwert in der alltäglichen Patientenversorgung bekommen. Die immer deutlicher werdenden neuroplastischen und neuroprotektiven Auswirkungen körperlichen Trainings sprechen dafür, aktivierende Therapien bei der Parkinson-Erkrankung früh im Krankheitsverlauf und nicht erst beim Auftreten funktionell relevanter Behinderungen einzusetzen.

Abstract

The major causes of disability in Parkinson’s disease (PD) are cognitive decline and motor aspects of the disease which are not improved by L-Dopa. There has been increasing evidence that vigorous exercise might favourably influence the course of Parkinson’s disease. In animal models of Parkinson’s disease physical exercise enhances the release of neurotrophic factors which is linked to neuroplasticity and neuroprotection leading to an improvement of motor symptoms. Numerous clinical studies suggest that the impairment caused by medication-refractory motor problems might be reduced by exercise therapy. Furthermore, exercised patients with PD can improve their cognitive scores. Exercise programmes lasting 1–6 months resulted in significant improvements of gait, posture, balance, and muscle strength. A few studies have shown positive effects on physical functioning and health-related quality of life. Most often, physiotherapy, walking, Nordic walking and high intensity resistance training have been applied. Beneficial effects of exercise on cognitive performance have also been shown in patients and in animal models of Parkinson’s disease. Higher levels of moderate to vigorous physical activities at ages 35–39 or in the past 10 years were associated with a future lower risk of PD. The neuronal mechanisms underlying the effects of exercise therapy on progression of PD are not completely understood. Nevertheless, based on the positive results of exercise therapy in clinical studies and basic research, exercise therapy should be implemented already in the early stages of Parkinson’s disease and not delayed to advanced stages.

Schlüsselwörter

Sport - M. Parkinson - Gang - Trainingsintensität - Funtionalität

Keywords

sports - Parkinson’s disease - gait - intensity of training - functionality

Full Text

References

Literatur
1 de Rijk MC, Launer LJ, Berger K et al. Prevalence of Parkinson’s disease in Europe: A collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group. Neurology 2000; 54 (Suppl. 05) S21-S23
2 Hughes AJ, Daniel S, Kilford L et al. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinicopathological study of 100 cases. J Neurol Neurosurg Psychiatry 1992; 55: 181-184
3 Gelb DJ, Oliver E, Gilman S et al. Diagnostic Criteria for Parkinson Disease. Arch Neurol 1999; 56: 33-39
4 Marsden CD. The mysterious motor function of the basal ganglia. Neurology 1982; 32: 514-539
5 Brotchie P, Iansek R, Horne MK. Motor function of the monkey globus pallidus. 1. Neuronal discharge and parameters of movement. Brain 1991; 114: 1667-1683
6 Georgiou N, Iansek R, Bradshaw JL et al. An evaluation of the role of internal cues in the pathogenesis of parkinsonian hypokinesia. Brain 1993; 116 (Pt 6) 1575-1587
7 Bennecke R, Rothwell JC, Dick JP et al. Performance of simultaneous movements in patients with Parkinson’s disease. Brain 1986; 109 (04) 739-757
8 Robichaud JA, Pfann KD, Vaillancourt DE et al. Force control and disease severity in Parkinson’s disease. Mov Disord 2005; 20: 441-450
9 Koller WC, Kase S. Muscle strength testing in Parkinson’s disease. Eur Neurol 1986; 25: 130-133
10 Bridgewater KJ, Sharpe MH. Trunk muscle training and early Parkinson’s Disease. Physiother Theor Pract 1997; 13: 139-153
11 Nogaki H, Fukusako T, Sasabe F et al. Muscle strength in early Parkinson’s disease. Mov Disord 1995; 10: 225-226
12 Pedersen SW, Oberg B. Dynamic strength in Parkinson’s disease. Eur Neurol 1993; 33: 97-102
13 Grimby L, Hannerz J. Disturbances in the voluntary recruitment order of anterior tibial motor units in bradykinesia of Parkinsonism. J Neurol Neurosurg Psychiatry 1974; 37: 47-54
14 Hayashi A, Kagamihara Y, Nakajima Y et al. Disorder in reciprocal innervation upon initiation of voluntary movement in patients with Parkinson’s disease. Exp Brain Res 1988; 70: 437-440
15 Saltin B, Landin S. Work capacity, muscle strength, and SDH activity in both legs of hemiparetic and patients with Parkinson’s disease. Scand J Clin Lab Invest 1975; 35: 531-538
16 Yanagawa S, Shindo M, Yanagisawa N. Muscular weakness in Parkinson’s disease. In: Streifler MB, Korczyn AD, Melamed E, Youdim MB. (eds.). Advances in Neurology: Parkinson’s disease-anatomy, pathology, and therapy. Vol 53. New York: Raven press; 1990: 259-269
17 Glendining DS, Enoka RM. Motor unit behaviour in Parkinson’s disease. Phys Ther 1994; 74: 61-70
18 Toole T, Hirsch MA, Forkink A et al. The effect of a balance and strength training program on Parkinsonism: a preliminary study. J Neurol Rehabil 2000; 14: 165-174
19 Morris ME, Martin CL, Schenkman ML. Striding out with Parkinson disease: evidence-based physical therapy for gait disorders. Phys Ther 2010; 90: 280-288
20 Fertl E, Doppelbauer A, Auff E. Physical activity and sports in Patients suffering from Parkinson’s disease in comparison with healthy seniors. J Neural Trans 1993; 5: 157-161
21 van Nimwegen M, Speelman AD, Hofman-van Rossum EJ et al. Physical inactivity in Parkinson’s disease. J Neurol 2011; 258: 2214-2221
22 Pickering RM, Grimbergen YA, Rigney U et al. A meta-analysis of six prospective studies of falling in Parkinson’s disease. Mov Disord 2007; 22: 1892-1900
23 Eijkeren van FJ, Reijmers RS, Kleinveld MJ et al. Nordic walking improves mobility in Parkinson’s disease. Mov Dis 2008; 23: 2239-2249
24 Quittenbaum B, Grahn B. Quality of life and pain in Parkinson’s disease: a controlled cross-sectional study. Parkinsonism and related Disorders 2004; 10: 129-136
25 Broetz D, Eichner M, Gasser T et al. Radicular and non-radicular back pain in Parkinson’s disease: A controlled study, Mov. Dis 2007; 22: 853-856
26 Etchepare F, Rozenberg S, Mirault T et al. Back problems in Parkinson’s disease: an underestimated problem. J Bone Surg 2006; 73: 298-302
27 Toole T, Park S, Hirsch M et al. The multicomponent nature of equilibrium in persons with parkinsonism: a regression approach. J Neural Transm Gen Sect 1996; 103: 561-580
28 Woods SP, Tröster AI. Prodromal frontal/executive dysfunction predicts incident dementia in Parkinson’s disease. J Int Neuropsychol Soc 2003; 9: 17-24
29 Goldman WP, Baty JD, Buckles VD et al. Cognitive and motor functioning in Parkinson disease: subjects with and without questionable dementia. Arch Neurol 1998; 55: 674-680
30 Hausdorff JM, Doninger GM, Springer S et al. A common cognitive profile in elderly fallers and patients with Parkinson’s disease: the prominence of impaired executive function and attention. Exp Aging Res 2006; 32: 411-429
31 Pendt LK, Reuter I, Müller H. Motor skill learning, retention, and control deficits in Parkinson’s disease. PLoS One 2011; 6: e21669
32 Bloem BR, Grimbergen YAM, Cramer M et al. Prospective assessment of falls in Parkinson’s disease. J Neurol 2001; 248: 950-958
33 Hely MA, Morris JL, Reid WGJ et al. Sydney Multicenter Study of Parkinson’s Disease: Non-L-Dopa–Responsive Problems Dominate at 15 Years. Mov Disord 2005; 20: 190-199
34 Mensink G. Bundes-Gesundheitssurvey: Körperliche Aktivität. Beiträge zur Gesundheitsberichterstattung des Bundes. Robert Koch-Institut; Berlin: 2003
35 Reuter I, Mehnert S, Leone P et al. Effects of Gymnastics, Walking and Nordic Walking in Parkinson’s disease. J Aging Res 2011; 2011: 232473
36 Goodwin VA, Richards SH, Taylor RS et al. The effectiveness of exercise intervention for people with Parkinson’s disease: A systematic review and meta-analysis. Mov Disord 2008; 23: 631-640
37 Jöbges M, Spittler-Schneiders H, Renner CI et al. Clinical relevance for rehabilitation programs for Parkinson’s disease. I: Non-symptom-specific therapeutic approaches. Parkinsonism Relat Disord 2007; 13: 195-202
38 Keus SHJ, Bloem BR, Hendricks EJM et al. Evidence-based analysis of physical therapy in Parkinson’s disease with recommendation for praxis and research. Mov Dis 2007; 22: 451-460
39 Deane KOH, Jones D, Playford ED et al. Physiotherapy versus placebo or no intervention in Parkinson’s disease. Cochrane database Syst Rev 2001; 1
40 Deane KOH, Ellis-Hill C, Jones D et al. Systematic review of paramedical therapies for Parkinson’s disease. Mov Dis 2002; 17: 984-991
41 Kwakkel G, de Goede CJT, van Wegen EEH. Impact of physical therapy for Parkinson’s disease: A critical review of the literature. Parkinsonism and Related Disorders 2007; 13: S478-S487
42 Rascol O, Goetz C, Koller W et al. Treatment interventions for Parkinson’s disease: an evidence based assessment. Lancet 4 2002; 359 (9317) 1589-1598
43 Ashburn A, Fazakarley L, Ballinger C et al. A randomised controlled trial of a home-based exercise programme to reduce risk of falling among people with Parkinson’s disease. J Neurol Neurosurg Psychiatry 2007; 78: 678-684
44 Bergen BL, Toole T, Ellliott RG et al. Aerobic exercise intervention improves aerobic capacity and movement initiation in Parkinson’s disease patients. Neurorehabilition 2002; 17: 161-168
45 Burini D, Farabollini B, Iacucci S et al. randomised controlled cross-over trial of aerobic training versus Qigong in advanced Parkinson’s disease. Europa Medicophys 2006; 42: 231-238
46 Cakit BD, Saracoglu M, Genc H et al. The effects of incremental speed-dependent treadmill training on postural instability and fear of falling in Parkinson’s disease. Clin Rehabil 2007; 21: 698-705
47 Comella CL, Stebbins GT, Brown-Toms N et al. Physical therapy and Parkinson’s disease: a controlled clinical trial. Neurology 1994; 44: 376-378
48 Dibble LE, Hale TF, Marcus RL et al. High intensity eccentric resistance training decreases bradykinesia and improves quality of life in persons with Parkinson’s disease: A preliminary study. Parkinsonism and Relat Disord 2009; 15: 752-757
49 Ebersbach G, Ebersbach A, Edler D et al. Comparing exercise in Parkinson’s disease-The Berlin LSVT® BIG Study. Mov Dis 2010; 25: 1902-1908
50 De Goede CJ, Keus SH, Kwakkel C et al. The effects of Physical Therapy in Parkinson’s disease: a research analysis. Arch Phys Med Rehabil 2001; 82: 509-515
51 Ellis T, de Goede CJ, Feldman RG et al. Efficacy of a physical therapy program in patients with Parkinson’s disease: a randomised controlled trial. Arch Phys Med Rehabil 2005; 86: 626-632
52 Goodwin VA, Richards SH, Henley W et al. An exercise intervention to prevent falls in people with Parkinson’s disease: a pragmatic randomised controlled trial. JNNP 2011-300919
53 Hass CJ, Collins MA, Juncos JL. Resistance training with creatine monohydrate improves upper-body strength in patients with Parkinson disease: a randomized trial. Neurorehabil Neural Repair 2007; 21: 107-115
54 Hirsch M, Toole T, Maitland CG et al. The effects of Balance Training and High-Intensity Resistance Training on Persons with idiopathic Parkinson’s Disease. Arch Phys Med. Rehabil 2003; 84: 1109-1117
55 Jöbges M, Heuschkel G, Pretzel C. Repetitive training of compensatory steps: a therapeutic approach of postural instability in Parkinson’s disease. J Neurol Neurosurg Psychiatry 2004; 75: 1682-1687
56 Keus SH, Bloem BR, van Hilten JJ et al. Effectiveness of physiotherapy in Parkinson’s disease: the feasibility of a randomised controlled trial. Parkinsonism Relat Disord 2007; 13: 115-121
57 Mak MK, Hui-Chan CW. Cued Task-specific training is better than exercise improving sit-to-stand in Patients with Parkinson’s disease. A randomized controlled trial. Mov Dis 2008; 23: 501-509
58 Marchese R, Diverio M, Zucchi F et al. The role of sensory cues in the rehabilitation of parkinsonian patients: a comparison of two physical therapy protocols. Mov Disord 2000; 15: 879-883
59 Miyai I, Fujimoto Y, Ueda Y et al. Treadmill training with body weight support: its effect on Parkinson’s disease. Arch Phys Med Rehabil 2000; 81: 849-852
60 Morris ME, Iansek R, Kirkwood B. A randomised controlled trial of movement strategies compared with exercise for people with Parkinson’s disease. Mov Disord 2009; 24: 64-71
61 Nieuwboer A, Kwakkel G, Rochester L et al. Cueing training in the home improves gait-related mobility in Parkinson’s disease: the RESCUE trial. J Neurol Neurosurg Psychiatry 2007; 78: 134-141
62 Palmer SS, Mortimer JA, Webster DD et al. Exercise therapy for Parkinson’s disease. Arch Phys Med Rehabil 1986; 67: 741-745
63 Pohl M, Rockstroh K, Ruckriem S et al. Immediate effects of speed-dependent treadmill training on gait parameters in early Parkinson’s disease. Arch Phys Med Rehabil 2003; 84: 1760-1766
64 Protas EJ, Mitchell K, Williams A et al. Gait and step training to reduce falls in Parkinson’s disease. NeuroRehabilitation 2005; 20: 183-190
65 Reuter I, Mehnert S, Oechsner M et al. Cognitive rehabilitation in Parkinson’s disease using neuropsychological training, transfer training and sports therapy. In diagnosics and rehabilitation of Parkinson’s disease. ED: Dushanova J. 2011: 257-286
66 Sage M, Almeida QJ. Symptom and gait changes after sensory attention focused exercise vs. aerobic training in Parkinson’s disease. Mov Dis 2009; 24: 1132-1138
67 Scandalis TA, Bosak A, Berliner JC et al. Resistance training and gait function in Patients with Parkinson’s disease. Am J Phys Med Rehabil 2001; 80: 38-43
68 Schenkmann M, Cutson TM, Kuchibhatla M et al. Exercise to improve spinal flexibility and function for people with Parkinson’s disease: a randomised controlled trial. J Am Geriatr Soc 1998; 4: 1207-1216
69 Schilling BK, Pfeiffer RF, LeDoux MS et al. Effects of Moderate- Volume, High-Load Lower-Body Resistance Training on Strength and Function in Persons with Parkinson’s Disease: A pilot Study. Parkinsons Dis 2010; 824734
70 Schmitz-Hübsch T, Derek P, Kielwein K et al. Qigong exercise for the symptoms of Parkinson’s disease: A randomized, controlled pilot study. Mov Disord 2006; 21: 543-548
71 Stallibrass C, Sissons P, Chalmers C. Randomised controlled trial of the Alexander technique for idiopathic Parkinson’s disease. Clin Rehabil 2002; 16: 695-708
72 Thaut MH, McIntosh GC, Rice R et al. Rhythmic auditory stimulation in gait training for Parkinson’s disease patients. Mov Disord 1996; 11: 193-200
73 Toole T, Maitland CG, Warren E et al. The effects of loading and unloading treadmill walking on balance, gait, fall risk, and daily function in Parkinsonism. NeuroRehabilitation 2005; 20: 307-322
74 Farley BG, Fox CM, Ramig L et al. Intensive amplitude-specific therapeutic approaches for Parkinson’s disease. Topics Ger Rehabil 2008; 24: 99-114
75 Platz T, Brown RG, Marsden CD. Training improves the speed of aimed movements in Parkinson’s disease. Brain 1998; 121: 505-514
76 Frenkel-Toledo S, Giladi N, Peretz C et al. Treadmill walking as an external pacemaker to improve gait rhythm and stability in Parkinson’s disease. Mov Disord 2005; 20: 1109-1114
77 Kamsma YPT, Brouwer WH, Lakke JPWF. Training of compensatory strategies for impaired gross motor skills in Parkinson’s disease. PhysiotherTheory Pract 1995; 11: 209-222
78 Yekutiel MP, Pinhasow A, Shahar G et al. A clinical trial of the re-education of movement in patients with Parkinson’s disease. Clin Rehab 1991; 5: 2007-2014
79 Combs SA, Diehl MD, Staples WH et al. Boxing training for patients with Parkinson disease: a case series. Phys Ther 2011; 91: 132-142
80 Hirsch MA, Farley BG. Exercise and neuroplasticity in persons living with Parkinson’s disease. Eur J Phys Rehab Med 2009; 45: 215-229
81 Tillerson JL, Cohen AD, Philhower J et al. Forced limb – use effects on the behavioural and neurochemical effects of 6-hydroxydopamine. J Neurosci 2001; 21: 4427-4435
82 Formisano R, Pratesi L, Modarelli FT et al. Rehabilitation and Parkinson’s disease. Scand J Rehabil Med 1992; 24: 157-160
83 Fritz B, Rombach S, Godau J et al. The influence of Nordic Walking training on sit-to-stand transfer in Parkinson patients. Gait & posture 2011; 34: 234-238
84 Tanaka K, De Quadros AC, Santos RF et al. Benefits of physical exercise on executive functions on older people with Parkinson’s disease. Brain Cogn 2009; 69: 435-441
85 Cruise KE, Bucks RS, Loftus AM et al. Exercise and Parkinson’s: benefits for cognition and quality of life. Acta Neurol Scand 2011; 123: 13-19
86 Allen NE, Sherrington C, Paul SS et al. Balance and falls in Parkinson’s disease: a meta-analysis of the effect of exercise and motor training. Mov Disord 2011; 26: 1605-1615
87 Scigliano G, Musicco M, Soliveri P et al. Reduced risk factors for vascular disorders in Parkinson’s disease. a case-control study. Stroke 2006; 37: 1184-1188
88 Nanhoe-Mahabier W, de Laat KF, Visser JE et al. Parkinson’s disease and comorbid vascular disease. Nat Rev Neurol 2009; 5: 533-541
89 Marcus BH, Williams DM, Dubbert PM et al. Physical activity intervention studies: what we know and what we need to know: a scientific statement from the American Heart association Counsil on Nutrition, Physical activity, and Metabolism (Subcommittee on Physical activity); Counsil on Cardiovascular disease in the Young; and the interdisciplinary Working Group on Quality of care and outcomes Research. Circulation 2006; 114: 2739-2752
90 Metkus Jr TS, Baughman KL, Thompson PD. Exercise prescription and primary prevention of cardiovascular disease. Circulation 2010; 121: 2601-2604
91 Stanley RK, Protas EJ, Jankovic J. Exercise performance in those having Parkinson’s disease. Med Sci Sports Exerc 1999; 31: 761-766
92 Christiansen CL, Schenkmann ML, McFann K et al. Walking economy in people with Parkinson’s disease. Mov Disord 2009; 24: 1481-1487
93 Herman T, Giladi N, Hausdorff JM. Treadmill training for the treatment of gait disturbances in people with Parkinson’s disease: a mini-review. J Neural Transm 2009; 116: 307-318
94 Miyai I, Fujimoto Y, Yamamoto H et al. Long-term effect of body weight-supported treadmill training in Parkinson’s disease: a randomized controlled trial. Arch Phys Med Rehabil 2002; 83: 1370-1373
95 Blake H, Mo P, Malik S et al. How effective are physical activity interventions for alleviating depression symptoms in older people? A systematic review. Clin Rehabil 2009; 23: 873-887
96 Riedel O, Klotsche J, Spottke A et al. Frequency of dementia, depression, and other neuropsychiatric symptoms in 1449 outpatients with Parkinson’s disease. J Neurol 2010; 257: 1073-1082
97 Rodrigues de Paula F, Teixeira-Salmela LF, Coelho de Morais Faria CD et al. Impact of an exercise program on physical, emotional, and social aspects of quality of life of individuals with Parkinson’s disease. Mov Disord 2006; 21: 1073-1077
98 Aarsland D, Andersen K, Larsen JP et al. Prevalence and characteristics of dementia in Parkinson disease: an 8-year prospective study. Arch Neurol 2003; 60: 387-392
99 Lautenschlager NT, Cox KL, Flicker L et al. Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a randomized trial. JAMA 2008; 300: 1027-1037
100 Angevaren M, Aufdemkampe G, Verhaar HJ et al. Physical activity and enhanced fitness to improve cognitive function in older people without known cognitive impairment. Cochrane Database Syst Rev 2008; 3 CD005381. Review
101 Larson EB, Wang L, Bowen JD et al. Exercise is associated with reduced risk for incident dementia among persons 65 years and older. Ann Intern Med 2006; 144: 73-81
102 Aguiar Jr AS, Castro AA, Moreira EL et al. Short bouts of mild-intensity physical exercise improve spatial learning and memory in aging rats: Involvement of hippocampal plasticity via AKT, CREB and BDNF signaling. Mech Ageing Dev 2011 132: 560-567
103 Mouradian MM, Juncos JL, Serrati C et al. Exercise and antiparkinsonian response to levodopa. Clin Neuropharmacol 1987; 10: 351-355
104 Goetz CG, Thelen JA, MacLeod CM et al. Blood levodopa levels and unified Parkinson’s disease rating scale function: with and without exercise. Neurology 1993; 43: 1040-1042
105 Carter JH, Nutt JG, Woodward WR. The effect of levodopa absorption. Neurology 1992; 42: 2042-2045
106 Reuter I, Harder S, Engelhardt M et al. The effect of pharmacokinetics and pharmacodynamics of levodopa. Mov Dis 2000; 15: 862-865
107 Tajiri N, Yasuhara T, Shingo T et al. Exercise exerts neuroprotective effects on Parkinson’s disease model of rats. Brain Res 2010; 1310: 200-207
108 Tillerson JL, Caudle WM, Reveron ME et al. Exercise induces behavioural recovery and attenuates neurochemical deficits in rodent model of Parkinson’s disease. Neuroscience 2003; 119: 899-911
109 Colcombe S, Kramer AF. Fitness effects on the cognitive function of older adults: A meta-analytic study. Psychological Science 2003; 14 (02) 125-130
110 Pothakos K, Kurz M, Lau Y-S. Restorative effect of endurance exercise on behavioural deficits in the chronic mouse model of Parkinson’s disease with severe neurodegeneration. BMC Neurosci 2009; 10: 6
111 Gerecke KM, Jiao Y, Pani A et al. Exercise protects against MPTP-induced neurotoxicity in mice. Brain Res 2010; 1341: 72-83
112 VanLeeuven JE, Petzinger GM, Walsh JP et al. Altered AMPA receptor expression with treadmill exercise in the 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine –lesioned mouse model of basal ganglia injury. J Neurosci Res 2010; 88: 650-668
113 Chauhan NB, Siegel GJ, Lee JM. Depletion of glial cell line-derived neurotrophic factor in substantia nigra neurons of Parkinson’s disease brain. J Chem Neuroanat 2001; 21: 277-288
114 Wu SY, Wang TF, Yu L. Running exercise protects the substantia nigra dopaminergic neurons against inflammation-induced degeneration via the activation of BDNF-signaling pathway. Brain Behav Immun 2011; 25: 135-146
115 Cohen AD, Tillerson JL, Smith AD et al. Neuroprotective effects of prior limb use in 6-hydroxydopamine treated rats: Possible role of GDNF. J Neurochem 2003; 85: 299-305
116 Petzinger GM, Walsh Akopian G. et al. Effects of treadmill exercise on dopaminergic transmission in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse model of basal ganglia injury. J Neurosci 2007; 27: 5291-5300
117 Fisher BE, Petzinger GM, Nixon K et al. Exercise-induced behavioural recovery in the 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-lesioned mouse basal ganglia. J Neurosci Res 2004; 77: 378-390
118 Vučković MG, Fisher B, Nacca A et al. Exercise elevates dopamine D2 receptor in a mouse model of Parkinson’s disease: in vivo imaging with [18F]fallpyride. Mov Disord 2010; 25: 2777-2784
119 Nichol KE, Parachikova AI, Cotman CW. Three weeks of running wheel exposure improves cognitive performance in the aged Tg2576 mouse. Behav Brain Res 2007; 184: 124-132
120 Parachikova A, Nichol KE, Cotman CW. Short-term exercise in aged Tg2576 mice alters neuroinflammation and improves cognition. Neurobiol Dis 2008; 1: 121-129
121 Ahmad SO, Park J-H, Stenho-Bittel L et al. Effects of endurance exercise on ventral tegmental area neurones in the chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and probenecid treated mice. Neurosci Lett 2009; 450: 102-105
122 O’Dell SJ, Gross NB, Fricks AN et al. Running wheel exercise enhances recovery from nigrostriatal dopamine injury without inducing neuroprotection. Neuroscience 2007; 144: 1141-1151
123 Xu Q, Park Y, Huang X et al. Physical activities and future risk of Parkinson disease. Neurology 2010; 75: 341-348
124 Sasco AJ, Paffenbarger Jr RS, Gendre I et al. The role of physical exercise in the occurrence of Parkinson’s disease. Arch Neurol 1992; 49: 360-365
125 Chen H, Zhang SM, Schwarzschild MA et al. Physical activity and the risk of Parkinson’s disease. Neurology 2005; 64: 664-669
126 Thacker EL, Chen H, Patel AV et al. Recreational physical activity and risk of Parkinson’s disease. Mov Disord 2008; 23: 69-74
127 Hu G, Jousilahti P, Nissinen A et al. Body mass index and the risk of Parkinson’s disease. Neurology 2006; 67: 1955-1959
128 Logroscino G, Sesso HD, Paffenberger HS et al. Physical activity and risk of Parkinson’s disease: a prospective cohort study. J Neurol Neurosurg Psychiatry 2006; 77: 1318-1322
129 Tsai CH, Lo SK, Lee LC et al. Environmental risk factors of young onset Parkinson’s disease: a case control study. Clin Neurol Neurosurg 2002; 104: 328-333
130 Uc EY, Doerschug K, Mehta S et al. Cardiovascular fitness and cognition in mild to moderate Parkinson’s disease. Neurology 2008; 70: A290
131 Fisher BE, Wu AD, Salem GJ et al. The effect of exercise training in improving motor performance and corticomotor excitability in people with early Parkinson’s disease. Arch Phys Med Rehabil 2008; 89: 1221-1229
132 Kuroda K, Tatara K, Takatorige T et al. Effect of physical exercise on mortality in Patients with Parkinson’s disease. Acta Neurol Scand 1992; 86: 55-59
133 Ahlskog JE. Does vigorous exercise have a neuroprotective effect in Parkinson’s disease?. Neurology 2011; 77: 288-294