Purpose/Hypothesis: Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by both motor and non-motor symptoms. Fatigue is one of the most common and disabling non-motor symptoms experienced by patients. Not only does fatigue negatively affect patients’ quality of life but also hinders their participation and compliance in rehabilitation. However, effective treatment of PD-fatigue is lacking. Evidence is mounting for beneficial effects of exercise for a variety of symptoms in patients with PD. The objective of this systematic review study was to evaluate the effect of exercise and physical therapy on reducing fatigue in PD. Materials and Methods: Databases including MEDLINE, PubMed, CINAHL Complete, and EMBASE were systematically searched. Eligibility criteria were that studies had: (1) enrolled patients with idiopathic PD, (2) administered exercise program as treatment for PD-fatigue, (3) compared the exercise intervention with usual care or conventional exercise, (4) measured fatigue, (5) used a design of randomized controlled trial, and (6) scored at least 4 out of 10 on Physiotherapy Evidence Database (PEDro) scale. Results: Twelve articles (N = 422) were included in this review, and all scored in the range from 4/10 to 8/10 with a mean of 6.3 (1.2) on the PEDro scale, indicating a fair to strong methodologic quality of the trials. Eight of the 12 studies showed significant improvements in fatigue scores (p < 0.05 to p < 0.000) in favor of intervention including but not limited to aerobic exercise, treadmill training, Nordic walking, exergaming, and home-based training program, as compared to controls. Discussion and Conclusions: Exercise and physical therapy are shown to be largely effective in reducing fatigue in patients with PD. Future studies using adequate sample sizes are needed to examine the optimal frequency, duration, and intensity of exercise to produce the most beneficial outcomes. Patients with PD may likely benefit from an integrated regimen of both PD-medication and physical therapy program. Clinical management of PD that will address both motor and non-motor symptoms is needed to maximize quality of life in people living with PD.
Bloem, B.R., Okun, M.S. and Klein, C. (2021) Parkinson’s Disease. The Lancet , 397, 2284-2303. https://doi.org/10.1016/s0140-6736(21)00218-x
Lang, A.E. and Espay, A.J. (2018) Disease Modification in Parkinson’s Disease: Current Approaches, Challenges, and Future Considerations. Movement Disorders , 33, 660-677. https://doi.org/10.1002/mds.27360
Kostić, V.S., Tomić, A. and Ječmenica-Lukić, M. (2016) The Pathophysiology of Fatigue in Parkinson’s Disease and Its Pragmatic Management. Movemen t Disorders Clinical Practice , 3, 323-330. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178705/
Smith, C., Olson, K., Hale, L.A., Baxter, D. and Schneiders, A.G. (2011) How Does Fatigue Influence Community-Based Exercise Participation in People with Multiple Sclerosis? Disability and Rehabilitation , 33, 2362-2371. https://doi.org/10.3109/09638288.2011.573054
Karpatkin, H. and Rzetelny, A. (2012) Effect of a Single Bout of Intermittent versus Continuous Walking on Perceptions of Fatigue in People with Multiple Sclerosis. International Journal of MS Care , 14, 124-131. https://doi.org/10.7224/1537-2073-14.3.124
Kluger, B.M., Herlofson, K., Chou, K.L., Lou, J., Goetz, C.G., Lang, A.E., et al . (2016) Parkinson’s Disease-Related Fatigue: A Case Definition and Recommendations for Clinical Research. Movement Disorders , 31, 625-631. https://doi.org/10.1002/mds.26511
Miyasaki, J.M. and Kluger, B. (2015) Palliative Care for Parkinson’s Disease: Has the Time Come? Current Neurology and Neuroscience Reports , 15, Article No. 26. https://doi.org/10.1007/s11910-015-0542-4
Mak, M.K., Wong-Yu, I.S., Shen, X. and Chung, C.L. (2017) Long-Term Effects of Exercise and Physical Therapy in People with Parkinson Disease. Nature Reviews Neurology , 13, 689-703. https://doi.org/10.1038/nrneurol.2017.128
Page, M.J., Moher, D., Bossuyt, P.M., Boutron, I., Hoffmann, T.C., Mulrow, C.D., et al . (2021) PRISMA 2020 Explanation and Elaboration: Updated Guidance and Exemplars for Reporting Systematic Reviews. BMJ , 372, n160. https://doi.org/10.1136/bmj.n160
Atan, T., Özyemişci Taşkiran, Ö., Bora Tokçaer, A., Kaymak Karataş, G., Karakuş Çalişkan, A. and Karaoğlan, B. (2019) Effects of Different Percentages of Body Weight-Supported Treadmill Training in Parkinson’s Disease: A Double-Blind Randomized Controlled Trial. Turkish Journal of Medical Sciences , 49, 999-1007. https://doi.org/10.3906/sag-1812-57
Canning, C.G., Allen, N.E., Dean, C.M., Goh, L. and Fung, V.S. (2012) Home-Based Treadmill Training for Individuals with Parkinson’s Disease: A Randomized Controlled Pilot Trial. Clinical Rehabilitation , 26, 817-826. https://doi.org/10.1177/0269215511432652
Cugusi, L., Solla, P., Serpe, R., Carzedda, T., Piras, L., Oggianu, M., et al . (2015) Effects of a Nordic Walking Program on Motor and Non-Motor Symptoms, Functional Performance and Body Composition in Patients with Parkinson’s Disease. NeuroRehabilitation : An International , Interdisciplinary Journal , 37, 245-254. https://doi.org/10.3233/nre-151257
Dashtipour, K., Johnson, E., Kani, C., Kani, K., Hadi, E., Ghamsary, M., et al . (2015) Effect of Exercise on Motor and Nonmotor Symptoms of Parkinson’s Disease. Parkinson ’ s Disease , 2015, Article ID: 586378. https://doi.org/10.1155/2015/586378
Granziera, S., Alessandri, A., Lazzaro, A., Zara, D. and Scarpa, A. (2020) Nordic Walking and Walking in Parkinson’s Disease: A Randomized Single-Blind Controlled Trial. Aging Clinical and Experimental Research , 33, 965-971. https://doi.org/10.1007/s40520-020-01617-w
Landers, M.R., Navalta, J.W., Murtishaw, A.S., Kinney, J.W. and Pirio Richardson, S. (2019) A High-Intensity Exercise Boot Camp for Persons with Parkinson Disease: A Phase II, Pragmatic, Randomized Clinical Trial of Feasibility, Safety, Signal of Efficacy, and Disease Mechanisms. Journal of Neurologic Physical Therapy , 43, 12-25. https://doi.org/10.1097/npt.0000000000000249
Ortiz-Rubio, A., Cabrera-Martos, I., Torres-Sánchez, I., Casilda-López, J., López-López, L. and Valenza, M.C. (2018) Effects of a Resistance Training Program on Balance and Fatigue Perception in Patients with Parkinson’s Disease: A Randomized Controlled Trial. Medicina Clínica ( English Edition ), 150, 460-464. https://doi.org/10.1016/j.medcle.2017.10.050
Ribas, C.G., Alves da Silva, L., Corrêa, M.R., Teive, H.G. and Valderramas, S. (2017) Effectiveness of Exergaming in Improving Functional Balance, Fatigue and Quality of Life in Parkinson’s Disease: A Pilot Randomized Controlled Trial. Parkinsonism & Related Disorders , 38, 13-18. https://doi.org/10.1016/j.parkreldis.2017.02.006
Rios Romenets, S., Anang, J., Fereshtehnejad, S., Pelletier, A. and Postuma, R. (2015) Tango for Treatment of Motor and Non-Motor Manifestations in Parkinson’s Disease: A Randomized Control Study. Complementary Therapies in Medicine , 23, 175-184. https://doi.org/10.1016/j.ctim.2015.01.015
Solla, P., Cugusi, L., Bertoli, M., Cereatti, A., Della Croce, U., Pani, D., et al . (2019) Sardinian Folk Dance for Individuals with Parkinson’s Disease: A Randomized Controlled Pilot Trial. The Journal of Alternative and Complementary Medicine , 25, 305-316. https://doi.org/10.1089/acm.2018.0413
Uc, E.Y., Doerschug, K.C., Magnotta, V., Dawson, J.D., Thomsen, T.R., Kline, J.N., et al . (2014) Phase I/II Randomized Trial of Aerobic Exercise in Parkinson Disease in a Community Setting. Neurology , 83, 413-425. https://doi.org/10.1212/wnl.0000000000000644
Wu, P., Lee, M., Wu, S., Ho, H., Chang, M., Lin, H., et al . (2021) Effects of Home-Based Exercise on Motor, Non-Motor Symptoms and Health-Related Quality of Life in Parkinson’s Disease Patients: A Randomized Controlled Trial. Japan Journal of Nursing Science , 18, e12418. https://doi.org/10.1111/jjns.12418
Frazzitta, G., Maestri, R., Ghilardi, M.F., Riboldazzi, G., Perini, M., Bertotti, G., et al . (2013) Intensive Rehabilitation Increases BDNF Serum Levels in Parkinsonian Patients: A Randomized Study. Neurorehabilitation and Neural Repair , 28, 163-168. https://doi.org/10.1177/1545968313508474
Forlenza, O.V., Diniz, B.S., Teixeira, A.L., Ojopi, E.B., Talib, L.L., Mendonça, V.A., et al . (2010) Effect of Brain-Derived Neurotrophic Factor Val66Met Polymorphism and Serum Levels on the Progression of Mild Cognitive Impairment. The World Journal of Biological Psychiatry , 11, 774-780. https://doi.org/10.3109/15622971003797241
Weinstein, G., Beiser, A.S., Choi, S.H., Preis, S.R., Chen, T.C., Vorgas, D., et al . (2014) Serum Brain-Derived Neurotrophic Factor and the Risk for Dementia: The Framingham Heart Study. JAMA Neurology , 71, 55-61. https://doi.org/10.1001/jamaneurol.2013.4781
Hirsch, M.A., van Wegen, E.E.H., Newman, M.A. and Heyn, P.C. (2018) Exercise-induced Increase in Brain-Derived Neurotrophic Factor in Human Parkinson’s Disease: A Systematic Review and Meta-Analysis. Translational Neurodegeneration , 7, Article No. 7. https://doi.org/10.1186/s40035-018-0112-1
Kaagman, D.G.M., van Wegen, E.E.H., Cignetti, N., Rothermel, E., Vanbellingen, T. and Hirsch, M.A. (2024) Effects and Mechanisms of Exercise on Brain-Derived Neurotrophic Factor (BDNF) Levels and Clinical Outcomes in People with Parkinson’s Disease: A Systematic Review and Meta-Analysis. Brain Sciences , 14, Article No. 194. https://doi.org/10.3390/brainsci14030194
Marusiak, J., Żeligowska, E., Mencel, J., Kisiel-Sajewicz, K., Majerczak, J., Zoladz, J., et al . (2015) Interval Training-Induced Alleviation of Rigidity and Hypertonia in Patients with Parkinson’s Disease Is Accompanied by Increased Basal Serum Brain-Derived Neurotrophic Factor. Journal of Rehabilitation Medicine , 47, 372-375. https://doi.org/10.2340/16501977-1931
Xia, R., Ronck, T.J., Sanft, R.A. and Eason, R.P. (2020) Association between Amount of Exercise and Fatigue in People with Parkinson’s Disease. EC Neurology , 12, 58-66.
Fisher, B.E., Li, Q., Nacca, A., Salem, G.J., Song, J., Yip, J., et al . (2013) Treadmill Exercise Elevates Striatal Dopamine D2 Receptor Binding Potential in Patients with Early Parkinson’s Disease. NeuroReport , 24, 509-514. https://doi.org/10.1097/wnr.0b013e328361dc13
Shah, C., Beall, E.B., Frankemolle, A.M.M., Penko, A., Phillips, M.D., Lowe, M.J., et al . (2016) Exercise Therapy for Parkinson’s Disease: Pedaling Rate Is Related to Changes in Motor Connectivity. Brain Connectivity , 6, 25-36. https://doi.org/10.1089/brain.2014.0328
Pavese, N., Metta, V., Bose, S.K., Chaudhuri, K.R. and Brooks, D.J. (2010) Fatigue in Parkinson’s Disease Is Linked to Striatal and Limbic Serotonergic Dysfunction. Brain , 133, 3434-3443. https://doi.org/10.1093/brain/awq268
Rueter, L.E. and Jacobs, B.L. (1996) A Microdialysis Examination of Serotonin Release in the Rat Forebrain Induced by Behavioral/Environmental Manipulations. Brain Research , 739, 57-69. https://doi.org/10.1016/s0006-8993(96)00809-8
Chaouloff, F., Laude, D., Guezennec, Y. and Elghozi, J.L. (1986) Motor Activity Increases Tryptophan, 5-Hydroxyindoleacetic Acid, and Homovanillic Acid in Ventricular Cerebrospinal Fluid of the Conscious Rat. Journal of Neurochemistry , 46, 1313-1316. https://doi.org/10.1111/j.1471-4159.1986.tb00656.x
Flöel, A. (2014) TDCS-Enhanced Motor and Cognitive Function in Neurological Diseases. NeuroImage , 85, 934-947. https://doi.org/10.1016/j.neuroimage.2013.05.098
Broeder, S., Nackaerts, E., Heremans, E., Vervoort, G., Meesen, R., Verheyden, G., et al . (2015) Transcranial Direct Current Stimulation in Parkinson’s Disease: Neurophysiological Mechanisms and Behavioral Effects. Neuroscience & Biobehavioral Reviews , 57, 105-117. https://doi.org/10.1016/j.neubiorev.2015.08.010
Hurley, R. and Machado, L. (2017) Using TDCS Priming to Improve Brain Function: Can Metaplasticity Provide the Key to Boosting Outcomes? Neuroscience & Biobehavioral Reviews , 83, 155-159. https://doi.org/10.1016/j.neubiorev.2017.09.029
Zhao, C. and Woodman, G.F. (2021) Converging Evidence That Neural Plasticity Underlies Transcranial Direct-Current Stimulation. Journal of Cognitive Neuroscience , 33, 146-157. https://doi.org/10.1162/jocn_a_01639
Kaski, D., Dominguez, R., Allum, J., Islam, A. and Bronstein, A. (2014) Combining Physical Training with Transcranial Direct Current Stimulation to Improve Gait in Parkinson’s Disease: A Pilot Randomized Controlled Study. Clinical Rehabilitation , 28, 1115-1124. https://doi.org/10.1177/0269215514534277