https://orcid.org/0000-0002-4757-914X
Figures
Abstract
Background
To determine the feasibility and effect of high-intensity interval training (HIIT) in individuals with Parkinson’s and their effect on symptom modification and progression.
Methods
We conducted this systematic review following the Preferred Reporting Items for systematic review and meta-analysis (PRISMA). All studies were searched in seven databases: MEDLINE (PubMed), Cochrane Central Register of Controlled Trials, Web of Science, EMBASE, SPORTDiscus, Virtual Health Library (VHL) and SCOPUS in September 2020 and updated in June 2023. The risk of bias was assessed by the Cochrane Collaboration tool and Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool. We used standardized mean difference (SMD) with a 95% confidence interval (CI) and random effects models, as well as the non-parametric Cochran’s Q test and I2 inconsistency test to assess heterogeneity.
Results
A total of 15 randomized clinical trials with 654 participants (mean age, 65.4 years). The majority of studies included high intensity training interventions versus moderate intensity, usual care, or control group. The meta-analysis comparing high-intensity exercise versus control group showed an improvement in the disease severity (MD = -4.80 [95%CI, -6.38; -3.21 high evidence certainty); maximum oxygen consumption (MD = 1.81 [95%CI, 0.36; 3.27] very low evidence certainty) and quality of life (MD = -0.54 [95%CI, -0.94; -0.13] moderate evidence certainty). The results showed that high-intensity exercise compared with moderate intensity exercise group showed a improve motor function and functional mobility measured by the TUG test (MD = -0.38 [95%CI, -0.91; 0.16] moderate evidence certainty) with moderate heterogeneity between studies.
Conclusion
High-intensity exercise performed in both continuous and interval modes when compared with control groups may provide motor function benefits for individuals with Parkinson’s disease. HIIT may be feasible, but the intensity of the exercise may influence individuals with Parkinson’s disease. However, there was a lack of evidence comparing high intensity and moderate intensity for this population, as the results showed heterogeneity.
Citation: Sena IGD, Costa AVd, Santos IKd, Araújo DPd, Gomes FTdS, Cavalcanti JRLdP, et al. (2023) Feasibility and effect of high-intensity training on the progression of motor symptoms in adult individuals with Parkinson’s disease: A systematic review and meta-analysis. PLoS ONE 18(11): e0293357. https://doi.org/10.1371/journal.pone.0293357
Editor: Michael Francis Salvatore, University of North Texas Health Science Center, UNITED STATES
Received: March 21, 2023; Accepted: October 10, 2023; Published: November 10, 2023
Copyright: © 2023 Sena et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper and its Supporting Information files.
Funding: The authors received no specific funding for this work.
Competing interests: The authors have declared that no competing interests exist.
Introduction
Parkinson’s disease (PD) is the second most common chronic neurodegenerative disorder in older adults, affecting about 1% of the world’s population over 60 years of age [1]. It is characterized by degenerating dopaminergic neurons in the substantia nigra pars compacta (SNpc), with a consequent dopamine deficit in the synapses of the central nervous system [2–4]. As a result of neurodegeneration, deficits such as tremor, muscle stiffness, bradykinesia, autonomic dysfunction, pain, and sleep disorders compromise the functional performance and quality of life of Parkinson’s patients, increasing their risk of morbidity and mortality [4–7]. There are several treatments for Parkinson’s disease including medicines, surgical treatment, and other therapies to increase the level of dopamine in the brain and help control non-movement symptoms. In addition, other therapies may manage the symptoms and modify the course of the disease and protect neurons against damage resulting from neurodegeneration [8–10]. In addition, therapies based on strength, cardiovascular and/or stretching exercise improve balance, flexibility, cardiorespiratory fitness, muscle strength, cognition, and quality of life in individuals with PD.
Studies highlight the potential benefits of low to moderate intensity exercise (37% to 63% of maximal oxygen consumption—VO2 max) for people with PD[10–14]. From this perspective, some issues have arisen about how exercise intensity affects its effectiveness to delay motor symptoms as disease progresses [9,15,16].
According to studies, exercise intensity is often measured using methods such as heart rate (HR), heart rate reserve (HRR) or oxygen uptake (VO2). There are several types of exercises and intensities; additionally, high-intensity is defined and categorized as vigorous effort (70%–90% of peak HR; 60%–84% of HRR; 60%–79% of peak VO2) or “very hard” effort (≥ 90% of peak HR; ≥ 85% of HRR; ≥ 80% of peak VO2) [17–19]. Moreover, the popular high-intensity interval training (HIIT) is interpreted as an exercise protocol which includes high-intensity exercise bouts interspersed with rest periods [20]. Evidence regarding PD suggests that these more intense exercises, above 70% of VO2peak, can induce activity-dependent neuroplasticity and produce more effective effects in delaying motor dysfunction when compared to low (37%-45% VO2) or moderate intensity exercises (45%-63% VO2) [16,21–23].
High-intensity exercise training may have greater effects on health parameters in obese and hypertensive patients when compared with moderate intensity [24,25], but the inclusion of higher training intensities as an adjuvant treatment for PD is not fully understood; especially considering that the motor limitations caused by the progressive symptoms already observed from stage II of the disease can impair the feasibility of performing the exercise, as is the case of those performed on a treadmill.
However, there is no consensus for prescribing the exercise intensity in PD, and variations in training protocols may have different effects, changing the physiological response of individuals to exercise [26,27]. Based on possibility of delays in symptom progression of the disease and the consequent improvement in functionality and quality of life that high-intensity physical exercise can present, and since there are no systematic reviews that we know of which have investigated this training modality in individuals with Parkinson’s disease, this study aims to review the evidence about the feasibility and effects of high-intensity exercise for people with Parkinson’s disease.
Methods
Study registration
This systematic review and meta-analysis were developed following the recommendations of Cochrane guidelines [28]. All report and preparation processes followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines [29]. The protocol for the construction stages of this review was registered in the International Prospective Register of Systematic Reviews (PROSPERO), under registration number CRD42020188473.
Eligibility criteria
We included randomized controlled trials following these criterias: Population: adults and older adults diagnosed with Parkinson’s disease; Intervention: exercise interventions classified as high-intensity; Comparator: moderate or low exercise or usual care (control group); Outcomes: The primary outcomes were progression of motor symptoms, as measured by the UPDRS, and feasibility of high-intensity physical exercise, as measured by adherence to training, participation rate until the end of the study, and achievement of the previously established target heart rate. Secondary outcomes: lower limb functionality measured by the TUG test, maximum oxygen consumption, and quality of life measured by the PDQ-39. We excluded studies which involved animals; systematic reviews and meta-analysis; dissertations; and theses.
Search methods for identification of studies
We performed a search in seven databases: Medline (PubMed), Cochrane Library, Web of Science, EMBASE, Library virtual of Health (BVS), SportDiscus and SCOPUS. No language or year restriction for articles were considered. The entire search process occurred in November 2020, but it was updated in June 2023. The search for descriptors used was performed in consultation with the Medical Subject Headings (MeSH), through the site of U.S. National Library of Medicine (NLM); Descriptors in Health Sciences (DeCS), and Embase Subject Headings (Emtree). We combined the subject, terms, synonyms, and keywords for “Parkinson’s disease” and “High-Intensity training” in the search strategy using the Boolean operator AND/OR. The search strategy is presented in Appendix A in S1 Appendix.
Study selection
Two authors screened the titles, abstracts and full texts independently (IGS and PKMM) using the Rayyan QRCI program [30]. All eligible studies were identified using the inclusion criteria. All duplicates were excluded after studies had been selected based on their titles and abstracts. Only full texts were evaluated to be considered potentially eligible. Any conflicts were resolved by a third reviewer (IATF).
Data extraction process
Two authors extracted all information independently using a template. We used standardized data extraction according to the following items: data on participants’ characteristics (number of participants, age, and PD stage), types of interventions (experimental and control group), outcomes measured and other details. A third reviewer (IATF) checked all data and ensured the process quality, and any differences were resolved by discussion and consensus. The entire process was conducted using the Rayyan QCRI program.
Risk of bias
We used the Cochrane Collaboration tool to assess the risk of bias (Cochrane Risk of Bias Tool) for the methodological quality of the studies included in this review [31]. According to this tool, each study was assessed independently based on the following seven domains: random sequence generation, allocation concealment, blinding of participants and professionals, blinding of outcome evaluators, incomplete outcomes, selective outcome reporting and other sources of bias. A response was generated for each of these domains based on three different categories: the high risk of bias, the risk of uncertain bias and the low risk of bias. Two authors independently (IGS and DPA) assessed risk of bias. When necessary, a third reviewer resolved disagreements (IKS).
Data synthesis
We planned to perform the meta-analysis comparing high intensity vs. moderate/low intensity exercise programs. We implemented standardized mean difference (SMD) with a 95% confidence interval (CI) and fixed-effect models for continuous results. The non-parametric Cochran’s Q test, which verified whether the training had identical effects, and the I2 inconsistency test were used to assess heterogeneity [32]. The p-value of 0.10 was used to indicate whether the heterogeneity was significant. The heterogeneity magnitude was assessed by calculating the I2, which ranges from 0% to 100%, indicating substantial heterogeneity when greater than 50% and considerable heterogeneity when greater than 75% [33]. A random effects model was used whenever there was a high degree of heterogeneity between studies [34]. The fixed effects model was used to estimate the change from baseline I 2 > 50% to explain the intervention effect size within the group. The studies were grouped according to the variables analyzed, considering high-intensity training versus moderate intensity training or high-intensity training versus the control group. The Review Manager software program (RevMan® 6.0) was used for all analyses.
Assessment of the quality of evidence
We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool to provide the quality of evidence and the strength of health recommendations for the intended outcomes[35]. The level of evidence in the GRADE method represents the confidence in the information that was used in the review, being performed for each analyzed outcome using the available set of evidence. The quality of evidence is classified into four levels: high, moderate, low and very low [36]. The data regarding the GRADE tool are described in Appendix B in S1 Appendix.
Results
Description of studies
A total 3,159 articles were found, but 1,366 were removed as duplicates. Next, 1,793 studies were evaluated in the screening stage by title and abstract for potential eligibility, with 1,723 excluded for not being thematically adequate. Thus, 70 studies with selection potential for full text reading were identified, and 55 studies were then excluded according to the eligibility criteria; as a result, 15 studies were selected for the review (Fig 1).
Characteristics of the included studies
The majority of studies were randomized controlled trials (RCTs) conducted in: Canada (2 studies) [37,38]; United States (4 studies) [23,26,39,40]; Hungary (2 studies) [41,42]; Brazil (2 studies) [43,44]; United Kingdom (2 studies) [45,46]; Spain [47], Denmark [48], and Columbia [49] (one each). The participants of the studies were recruited from clinical health centers at universities, hospitals, and clinics in several countries. The sample sizes range between 10 and 128 participants, mean average age was 65.4 years and ranged across studies from 30 and 86 years, men and women, to whom the mild (1–2), moderate (3) and severe (4) stages of Parkinson’s disease were attributed by the Hoehn and Yahr classification, with only one study which did not report the participants’ Hoen & Yahr classification stage [44]. Regarding adjustments for confounding factors, 14 studies (48.2%) showed a high variation in the age of the participants, which is a potentially modifying factor of symptoms and responses to training (see Table 1).
Characteristics of interventions
The interventions varied widely among the 15 studies. Each study included high-intensity exercise protocols in different modalities, including bike training, stationary recumbent bike, walk, jogging and treadmill. Some studies combined HIIT and strength, power, flexibility, balance, cardiorespiratory endurance, and functional training. The majority of studies compared high-intensity training with moderate-intensity training, control group or groups that performed only usual care[56–58,60–64], classified as low-intensity training, and there was additionally a combination of high intensity training with strength training and balance; only one study did not compare with another group.
A total of 15 studies used maximum heart rate (HRmax) to assess training intensity, characterizing high intensity training when the values were above 70% HRmax. Only two of the studies measured the training intensity with the Borg Rating of Perceived Exertion scale [65], in which values above 15 characterized high-intensity training.
The training period length varied widely across the 15 studies; six studies had 12 weeks of training with three sessions per week. Two studies used 8 weeks of training, 24 months, 32 weeks, 26 weeks, 3 weeks, 5 weeks, 24 sessions and 3 sessions (each study). The average weekly frequency ranged from two to three days, and session duration ranged from 25 to 60 minutes of training. The intervention characteristics are described in Table 2.
Characteristics of outcomes
The feasibility of high intensity training was analyzed by adherence to training percentages and by reaching the previously determined target maximum heart rate (HRmax). The HRmax target reached between the studies ranged from 61% to 100%, and these values refer to the study with the lowest and the highest rates of volunteers who reached the expected intensity, respectively. The results regarding adherence to training ranged from 66% to 100% participation until the end of the study, with losses reported by dropouts (ranged from 1 to 8) not related to the training protocol, such as changing the city and death from causes not related to the exercises.
Motor function assessed by the motor subscale of the Unified Parkinson’s Disease Rating Scale (MD-UPDRS) was used by 11 studies, and the assessment of maximum oxygen consumption (VO2) was measured by six studies using cardiopulmonary exercise testing system (COSMED Srl, Rome, Italy).
The results of the studies related to improvement in motor scores on the MD-UPDRS show that high-intensity training can delay the progression of motor symptoms in Parkinson’s disease. Other parameters which also influence disease progression and that are related to performance showed significant improvement, such as VO2peak, mobility and functionality of the lower limbs measured by Time Up and Go (TUG) test [66] was included in four studies, and cardiorespiratory fitness assessed by the 6-Minute Walk Test (6MWT) was used in two studies. Furthermore, other important findings such as improved quality of life evaluated by the Parkinson’s Disease Questionnaire (PDQ-39) [67] was included in five studies and increased levels of circulating BDNF in people with PD after a high-intensity training period were also observed.
Risk of bias in included studies
The risk of bias of all the studies (by domain items) was found as follows: all studies were classified as low risk of bias for random sequence generation (randomization), since they allocated their participants at random and described how this allocation was performed; one study was at high risk of bias for the allocation concealment item (which describes whether the study was adequately randomized), because they only used a random list of numbers generated by an open randomization process; one study had a high risk of bias in blinding the participants and professionals because they did not describe how the double-blind study proceeded, nor did the study have blinding in the assessments performed during the research, which made the outcome susceptible to influence from the lack of blinding; only one study had a high risk of bias for the item blinding of outcome evaluators, because there was no blind assessment of the outcomes, and the assessed outcomes are influenced by the lack of blinding; one study was assessed as unclear risk of bias for the item incomplete outcomes and selective outcome report, because not all results of important outcomes were described; lastly, three studies had a high risk of bias and 12 studies had a moderate risk of bias for other sources, both related to the study design (Fig 2).
Meta-analysis
High-intensity exercise vs control group.
Progression of motor symptoms. The Unified Parkinson’s Disease Rating Scale (UPDRS) was used in 11 studies to assess symptom progression and delays in the disease, but only 7 studies reassessed the volunteers from baseline changes. This scale is a validated tool to assess the severity of Parkinson’s disease, monitoring the progression of symptoms and the effectiveness of the treatments employed. This scale is divided into four parts: (1) mental activity, behavior and mood; (2) activities of daily living (ADLs); (3) motor exploration; and (4) complications of drug therapy [68]. The representation for decreasing the progression of the disease is indicated by the decrease in the scores of each item.
Six studies with 210 volunteers were included to analyze the effect of high intensity exercise versus control group on the progression of motor symptoms observed using UPDRS (Fig 3). The meta-analysis showed an improvement with statistical significance in the disease severity (P< 0.00001), with a balance of -4.80 points in the total scores (95%CI, -6.38; -3.21), which favored the volunteers of high-intensity exercise with high evidence certainty (Fig 3).
Maximum oxygen consumption.
Cardiorespiratory fitness determines an individual’s ability to sustain dynamic exercises of moderate and high intensities for a long period of time, in addition to providing information on morbidity prognosis and capacity to respond to treatment in certain pathologies [69]. The current gold standard for analyzing cardiorespiratory fitness is the direct measurement of VO2peak.
Four studies with low risk of bias totaling 164 volunteers were included to analyze the effect of high-intensity exercise versus control group in the assessment of maximal oxygen consumption (VO2peak) (Fig 4). The meta-analysis showed an improvement in statistical significance in VO2peak (P<0.0007), with an increase in oxygen consumption favoring the high-intensity exercise volunteers [1.78 l/m (95%CI, 0.82; 2.75), along with high heterogeneity (82%) and very low evidence certainty.
Quality of life.
The chronic and progressive nature of PD negatively affects the quality of the daily life activities of PD patients and consequently their quality of life [4]. As an indicator of PD progression and management, quality of life assessment is considered an important result for treating the disease [70]. The 39-item Questionnaire for Parkinson’s disease (PDQ-39) is a validated and widely used instrument for this assessment composed of eight scales that assess mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and body discomfort. Improvement in the quality of life is represented by a decrease in the score of each item [67].
Three studies with 100 volunteers were included to analyze the effect of high intensity exercise versus control group on quality of life by the PDQ-39 (Fig 5). The meta-analysis showed an improvement with statistical significance in quality of life (P = 0.001), with a balance of -0.59 points in the total scores (95%CI, -0.94; -0.13), which favored the high-intensity exercise volunteers and showed moderate evidence certainty.
High-intensity exercise vs moderate intensity exercise.
Progression of motor symptoms. Five studies with 219 volunteers were included to analyze the effect of high intensity exercise versus moderate intensity exercise on UPDRS (Fig 6). The meta-analysis showed an improvement with statistical significance in the disease severity (P<0.03), with a balance of -2.70 points in the total scores (95%CI, -5.06; -0.33), which favored the high-intensity exercise volunteers (Fig 3), with moderate heterogeneity.
Functionality mobility
Functional performance measures for people with Parkinson’s disease (PD) are necessary and correlate with disease progression, as motor changes caused by progressive disease symptoms resulting from neuronal degeneration are associated with the decline in functional capacity of these individuals [2].
The Time Up and Go (TUG) test was applied to assess basic functional mobility, which analyzed the number of required steps from each individual to perform the activity “getting up from a chair which has arms, walking 3-meters distance and returning to the chair”, considering that improvement for the test is indicated by decreasing the time spent to perform the activity, with higher values of time and number of steps representing a greater risk for falls [66].
Three studies with 64 volunteers were included to analyze the effect of high-intensity exercise versus moderate intensity exercise on the TUG test (Fig 7). The meta-analysis showed no statistical significance in functional mobility (P = 0.33), with a balance of -0.38 seconds to perform the TUG test (95%CI, -0.91; 0.16, moderate evidence certainty), when compared to moderate intensity exercises.
Discussion
Results from this systematic review and meta-analysis indicate that prescription of high-intensity exercise for individuals with PD may be feasible, in which the volunteers reached the previously established HRmax target for exercise, which can be considered a good adjuvant treatment of the disease to improve symptoms. However, these findings need more investigate about adherence and adverse events, a few studies reported this information with details. The analysis of the effect of the interventions identified potentially changes in motor symptom and functional mobility after HIIT performed in continuous or interval mode. This finding is consistent and clinically important, where usually symptoms that causes progressive losses related to mobility and functionality, and these predict decreases in quality of life and increase in mortality [27]. Studies have observed that usual exercise (i.e. walking endurance training) is recommended and considered a functional activity for people with PD [71]. In addition, individuals with PD invariably experience declines in balance and gait, and exercise can minimize these symptoms, improving physical functioning [72]. Therefore, delays in disease progression, which were higher in high-intensity training and correlate with functionality and independence, reinforce its effectiveness.
The meta-analysis for the cardiorespiratory fitness results showed a significant increase in the maximum oxygen consumption in individuals who trained at high intensity, both in the interval and continuous modality. Studies which related aerobic exercise with VO2peak values corroborate our results, demonstrating that cardiopulmonary function and physical fitness improved rapidly after training in individuals with PD [70,73–75].
Our meta-analysis also showed a significant improvement in quality of life for those who engaged in high-intensity exercise when compared to those who did not perform any exercise, supporting the results of previously published meta-analysis [14,70,76,77]. Common comorbidities such as depression, functional and cognitive decline in PD, which gradually reduce individuals’ quality of life, require training methods to support clinical treatment and reduce negative emotions caused by the disease [70].
Improvements related to the non-motor symptoms of PD were also evidenced after high-intensity training [21,38,43,44,78]. Although considered a movement disorder, non-motor manifestations such as autonomic dysfunction are also responsible for increasing the general burden of parkinsonian morbidity and mortality, further aggravating the clinical picture and limiting exercise performance, making the challenge of treating the disease even greater [2,79,80].
Endothelial reactivity, a non-motor symptom resulting from autonomic dysfunction and an important marker for assessing cardiovascular risk, improved significantly after high-intensity exercise performed in an interval manner (HIIT). This result probably suggests that alternating intensity during HIIT beneficially affected the shear stress in the arterial wall and produced better molecular responses, such as increased endothelial reactivity, since there were no improvements after exercise performed in this same study [25].
High-intensity exercise also demonstrated a greater impact on BDNF regulation than moderate-intensity exercise, increasing circulating BDNF levels after training [21,39,78]. These findings are important for prescribing training for people with neurodegenerative diseases, since BDNF is a factor that provides neuroprotection and cerebral neurodegeneration, serving as a therapeutic agent, and improving the survival of dopaminergic neurons and directly influencing motor performance [81,82]. However, providing physical activity/ exercises in different intensities may be alternatives suggested in the literature to reduce all negative impacts in people with PD [83,84].
This systematic review has several limitations. A major limitation was the lack of details on adherence and adverse events in the included studies. Another limitation was differences and heterogeneity in the types of exercise programs, which included different modes of delivery and intensities. Different high-intensity types of exercises were reported across studies: continuous training, interval training, or a combination of both modalities. Methodological rigor was also a limiting factor, with some publications showing biases such as non-blinding of evaluators and incomplete results, which in turn confuse other researchers wishing to reproduce the study.
Conclusion
In conclusion, this review has shown that high-intensity exercise performed in both continuous and interval modes may provide motor function benefits for individuals with Parkinson’s disease. In this sense, it is observed that HIIT may be feasible, further studies are needed to establish the minimal consensus about patients with Parkinson disease can tolerate. The combination of high and moderate intensity may result in greater benefit and requires further investigation. Furthermore, it is important to mention that exercise should be an integral part of therapy for people with Parkinson’s disease, always in conjunction with adjuvant treatment.
References
- 1. Dorsey E, Sherer T, Okun MS, Bloem BR. The emerging evidence of the Parkinson pandemic. Journal of Parkinson’s disease. 2018;8: S3–S8. pmid:30584159
- 2. Armstrong MJ, Okun MS. Diagnosis and treatment of Parkinson disease: a review. Jama. 2020;323: 548–560. pmid:32044947
- 3. De Araujo DP, Lobato RDFG, Cavalcanti JRLDP, Sampaio LRL, Araújo PVP, Silva MCC, et al. The contributions of antioxidant activity of lipoic acid in reducing neurogenerative progression of Parkinson’s disease: a review. International Journal of Neuroscience. 2011;121: 51–57. pmid:21126109
- 4. Barbieri FA, Rinaldi NM, Santos PCR, Lirani-Silva E, Vitorio R, Teixeira-Arroyo C, et al. Functional capacity of Brazilian patients with Parkinson’s disease (PD): relationship between clinical characteristics and disease severity. Archives of Gerontology and Geriatrics. 2012;54: e83–e88. pmid:21963176
- 5. Rodrigues RAS, Teodózio MM, Espinosa MM, Fett WCR, Melo CD, Fett CA. Timed up and go test and self-perceived health in elderly: population-based study. Revista Brasileira de Cineantropometria & Desempenho Humano. 2018;20: 247–257.
- 6. Kanegusuku H, Silva-Batista C, Peçanha T, Nieuwboer A, Silva ND Jr, Costa LA, et al. Blunted maximal and submaximal responses to cardiopulmonary exercise tests in patients with Parkinson disease. Archives of physical medicine and rehabilitation. 2016;97: 720–725. pmid:26780469
- 7. Hayes MT. Parkinson’s disease and parkinsonism. The American journal of medicine. 2019;132: 802–807. pmid:30890425
- 8. Espay AJ, Lang AE. Common myths in the use of levodopa in Parkinson disease: when clinical trials misinform clinical practice. JAMA neurology. 2017;74: 633–634. pmid:28459962
- 9. Alberts JL, Linder SM, Penko AL, Lowe MJ, Phillips M. It is not about the bike, it is about the pedaling: forced exercise and Parkinson’s disease. Exercise and sport sciences reviews. 2011;39: 177–186. pmid:21799425
- 10. Goodwin VA, Richards SH, Taylor RS, Taylor AH, Campbell JL. The effectiveness of exercise interventions for people with Parkinson’s disease: A systematic review and meta‐analysis. Movement disorders. 2008;23: 631–640. pmid:18181210
- 11. Speelman AD, Van De Warrenburg BP, Van Nimwegen M, Petzinger GM, Munneke M, Bloem BR. How might physical activity benefit patients with Parkinson disease? Nature Reviews Neurology. 2011;7: 528–534. pmid:21750523
- 12. Wang S-Y, Wu S-L, Chen T-C, Chuang C-S. Antidiabetic agents for treatment of Parkinson’s disease: a meta-analysis. International Journal of Environmental Research and Public Health. 2020;17: 4805. pmid:32635358
- 13. Ellis T, Cavanaugh JT, Earhart GM, Ford MP, Foreman KB, Fredman L, et al. Factors associated with exercise behavior in people with Parkinson disease. Physical therapy. 2011;91: 1838–1848. pmid:22003171
- 14. dos Santos Delabary M, Komeroski IG, Monteiro EP, Costa RR, Haas AN. Effects of dance practice on functional mobility, motor symptoms and quality of life in people with Parkinson’s disease: a systematic review with meta-analysis. Aging clinical and experimental research. 2018;30: 727–735. pmid:28980176
- 15. Hoehn MM, Yahr MD. Parkinsonism: onset, progression, and mortality. Neurology. 1998;50: 318.
- 16. Seppi K, Ray Chaudhuri K, Coelho M, Fox SH, Katzenschlager R, Perez Lloret S, et al. Update on treatments for nonmotor symptoms of Parkinson’s disease—an evidence‐based medicine review. Movement Disorders. 2019;34: 180–198. pmid:30653247
- 17. Marriott CFS, Petrella AFM, Marriott ECS, Boa Sorte Silva NC, Petrella RJ. High-Intensity Interval Training in Older Adults: a Scoping Review. Sports Medicine—Open. 2021;7: 49. pmid:34279765
- 18. Norton K, Norton L, Sadgrove D. Position statement on physical activity and exercise intensity terminology. Journal of science and medicine in sport. 2010;13: 496–502. pmid:20005170
- 19. Vanhees L, Geladas N, Hansen D, Kouidi E, Niebauer J, Reiner Z, et al. Importance of characteristics and modalities of physical activity and exercise in the management of cardiovascular health in individuals with cardiovascular risk factors: recommendations from the EACPR. Part II. European journal of preventive cardiology. 2012;19: 1005–1033. pmid:22637741
- 20. Gibala MJ, Gillen JB, Percival ME. Physiological and health-related adaptations to low-volume interval training: influences of nutrition and sex. Sports Medicine. 2014;44: 127–137. pmid:25355187
- 21. Callaghan RC, Cunningham JK, Sajeev G, Kish SJ. Incidence of Parkinson’s disease among hospital patients with methamphetamine-use disorders. Movement Disorders. 2010;25: 2333–2339. pmid:20737543
- 22. Landers MR, Navalta JW, Murtishaw AS, Kinney JW, Pirio Richardson S. 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. 2019;43: 12–25. pmid:30531382
- 23. Fisher BE, Li Q, Nacca A, Salem GJ, Song J, Yip J, et al. Treadmill exercise elevates striatal dopamine D2 receptor binding potential in patients with early Parkinson’s disease. NeuroReport. 2013;24: 509–514. pmid:23636255
- 24. Guimarães GV, Ciolac EG, Carvalho VO, D’Avila VM, Bortolotto LA, Bocchi EA. Effects of continuous vs. interval exercise training on blood pressure and arterial stiffness in treated hypertension. Hypertension Research. 2010;33: 627–632. pmid:20379194
- 25. Ciolac EG. High-intensity interval training and hypertension: maximizing the benefits of exercise? American journal of cardiovascular disease. 2012;2: 102. pmid:22720199
- 26. Schenkman M, Moore CG, Kohrt WM, Hall DA, Delitto A, Comella CL, et al. Effect of High-Intensity Treadmill Exercise on Motor Symptoms in Patients With De Novo Parkinson Disease. JAMA Neurology. 2018;75: 219. pmid:29228079
- 27. Rafferty MR, Schmidt PN, Luo ST, Li K, Marras C, Davis TL, et al. Regular exercise, quality of life, and mobility in Parkinson’s disease: a longitudinal analysis of national Parkinson foundation quality improvement initiative data. Journal of Parkinson’s disease. 2017;7: 193–202.
- 28.
Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al. Cochrane handbook for systematic reviews of interventions. John Wiley & Sons; 2019.
- 29. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Bmj. 2021;372.
- 30. Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan—a web and mobile app for systematic reviews. Systematic reviews. 2016;5: 210. pmid:27919275
- 31. Higgins JPT, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. Bmj. 2011;343: d5928. pmid:22008217
- 32. Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta‐analysis. Statistics in medicine. 2002;21: 1539–1558. pmid:12111919
- 33. Ioannidis JPA. Interpretation of tests of heterogeneity and bias in meta‐analysis. Journal of evaluation in clinical practice. 2008;14: 951–957. pmid:19018930
- 34. Hedges L V. A random effects model for effect sizes. Psychological bulletin. 1983;93: 388.
- 35. Zhang Y, Coello PA, Guyatt GH, Yepes-Nuñez JJ, Akl EA, Hazlewood G, et al. GRADE guidelines: 20. Assessing the certainty of evidence in the importance of outcomes or values and preferences—inconsistency, imprecision, and other domains. Journal of Clinical Epidemiology. 2019;111: 83–93. pmid:29800687
- 36. Guyatt GH, Oxman AD, Kunz R, Woodcock J, Brozek J, Helfand M, et al. GRADE guidelines: 8. Rating the quality of evidence—indirectness. Journal of clinical epidemiology. 2011;64: 1303–1310. pmid:21802903
- 37. Duchesne C, Gheysen F, Bore A, Albouy G, Nadeau A, Robillard ME, et al. Influence of aerobic exercise training on the neural correlates of motor learning in Parkinson’s disease individuals. NeuroImage: Clinical. 2016;12: 559–569. pmid:27689020
- 38. Duchesne C, Lungu O, Nadeau A, Robillard ME, Boré A, Bobeuf F, et al. Enhancing both motor and cognitive functioning in Parkinson’s disease: Aerobic exercise as a rehabilitative intervention. Brain and Cognition. 2015;99: 68–77. pmid:26263381
- 39. Shulman LM, Katzel LI, Ivey FM, Sorkin JD, Favors K, Anderson KE, et al. Randomized clinical trial of 3 types of physical exercise for patients with Parkinson disease. JAMA neurology. 2013;70: 183–190. pmid:23128427
- 40. Uc EY, Doerschug KC, Magnotta V, Dawson JD, Thomsen TR, Kline JN, et al. Phase I/II randomized trial of aerobic exercise in Parkinson disease in a community setting. Neurology. 2014;83: 413–425. pmid:24991037
- 41. Tollár J, Nagy F, Hortobágyi T. Vastly different exercise programs similarly improve parkinsonian symptoms: a randomized clinical trial. Gerontology. 2019;65: 120–127. pmid:30368495
- 42. Tollár J, Nagy F, Kovács N, Hortobágyi T. Two-Year Agility Maintenance Training Slows the Progression of Parkinsonian Symptoms. Medicine and science in sports and exercise. 2019;51: 237–245. pmid:30303934
- 43. Fiorelli CM, Ciolac EG, Simieli L, Silva FA, Fernandes B, Christofoletti G, et al. Differential Acute Effect of High-Intensity Interval or Continuous Moderate Exercise on Cognition in Individuals With Parkinson’s Disease. Journal of Physical Activity and Health. 2019;16: 157–164. pmid:30626260
- 44. Fernandes B, Barbieri FA, Arthuso FZ, Silva FA, Moretto GF, Imaizumi LFI, et al. High-intensity interval versus moderate-intensity continuous training in individuals with Parkinson’s disease: hemodynamic and functional adaptation. Journal of Physical Activity and Health. 2020;17: 85–91. pmid:31810064
- 45. O’Callaghan A, Harvey M, Houghton D, Gray WK, Weston KL, Oates LL, et al. Comparing the influence of exercise intensity on brain-derived neurotrophic factor serum levels in people with Parkinson’s disease: a pilot study. Aging Clinical and Experimental Research. 2020;32: 1731–1738. pmid:31606860
- 46. Harvey M, Weston KL, Gray WK, O’Callaghan A, Oates LL, Davidson R, et al. High-intensity interval training in people with Parkinson’s disease: a randomized, controlled feasibility trial. Clinical Rehabilitation. 2019;33: 428–438. pmid:30514114
- 47. Cancela JM, Mollinedo I, Montalvo S, Vila Suárez ME. Effects of a High-Intensity Progressive-Cycle Program on Quality of Life and Motor Symptomatology in a Parkinson’s Disease Population: A Pilot Randomized Controlled Trial. Rejuvenation Research. 2020;23: 508–515. pmid:32336211
- 48. Morberg BM, Jensen J, Bode M, Wermuth L. The impact of high intensity physical training on motor and non-motor symptoms in patients with Parkinson’s disease (PIP): a preliminary study. NeuroRehabilitation. 2014;35: 291–298. pmid:24990028
- 49. Segura C, Eraso M, Bonilla J, Mendivil CO, Santiago G, Useche N, et al. Effect of a High-Intensity Tandem Bicycle Exercise Program on Clinical Severity, Functional Magnetic Resonance Imaging, and Plasma Biomarkers in Parkinson’s Disease. Frontiers in neurology. 2020;11: 656. pmid:32793096
- 50. Cancela JM, Mollinedo I, Montalvo S, Vila Suárez ME. Effects of a High-Intensity Progressive-Cycle Program on Quality of Life and Motor Symptomatology in a Parkinson’s Disease Population: A Pilot Randomized Controlled Trial. Rejuvenation Res. 2020;23: 508–515. pmid:32336211
- 51. Duchesne C, Lungu O, Nadeau A, Robillard ME, Boré A, Bobeuf F, et al. Enhancing both motor and cognitive functioning in Parkinson’s disease: Aerobic exercise as a rehabilitative intervention. Brain Cogn. 2015;99: 68–77. pmid:26263381
- 52. Duchesne C, Gheysen F, Bore A, Albouy G, Nadeau A, Robillard ME, et al. Influence of aerobic exercise training on the neural correlates of motor learning in Parkinson’s disease individuals. Neuroimage Clin. 2016;12: 559–569. pmid:27689020
- 53. Uc EY, Doerschug KC, Magnotta V, Dawson JD, Thomsen TR, Kline JN, et al. Phase I/II randomized trial of aerobic exercise in Parkinson disease in a community setting. Neurology. 2014;83: 413–425. pmid:24991037
- 54. Fernandes B, Barbieri FA, Arthuso FZ, Silva FA, Moretto GF, Imaizumi LFI, et al. High-intensity interval versus moderate-intensity continuous training in individuals with Parkinson’s disease: hemodynamic and functional adaptation. J Phys Act Health. 2020;17: 85–91. pmid:31810064
- 55. Fiorelli CM, Ciolac EG, Simieli L, Silva FA, Fernandes B, Christofoletti G, et al. Differential Acute Effect of High-Intensity Interval or Continuous Moderate Exercise on Cognition in Individuals With Parkinson’s Disease. J Phys Act Health. 2019;16: 157–164. pmid:30626260
- 56. Fisher BE, Li Q, Nacca A, Salem GJ, Song J, Yip J, et al. Treadmill exercise elevates striatal dopamine D2 receptor binding potential in patients with early Parkinson’s disease. Neuroreport. 2013;24: 509–514. pmid:23636255
- 57. Harvey M, Weston KL, Gray WK, O’Callaghan A, Oates LL, Davidson R, et al. High-intensity interval training in people with Parkinson’s disease: a randomized, controlled feasibility trial. Clin Rehabil. 2019;33: 428–438. pmid:30514114
- 58. Morberg BM, Jensen J, Bode M, Wermuth L. The impact of high intensity physical training on motor and non-motor symptoms in patients with Parkinson’s disease (PIP): a preliminary study. NeuroRehabilitation. 2014;35: 291–298. pmid:24990028
- 59. O’Callaghan A, Harvey M, Houghton D, Gray WK, Weston KL, Oates LL, et al. Comparing the influence of exercise intensity on brain-derived neurotrophic factor serum levels in people with Parkinson’s disease: a pilot study. Aging Clin Exp Res. 2020;32: 1731–1738. pmid:31606860
- 60. Schenkman M, Moore CG, Kohrt WM, Hall DA, Delitto A, Comella CL, et al. Effect of High-Intensity Treadmill Exercise on Motor Symptoms in Patients With De Novo Parkinson Disease. JAMA Neurol. 2018;75: 219. pmid:29228079
- 61. Segura C, Eraso M, Bonilla J, Mendivil CO, Santiago G, Useche N, et al. Effect of a High-Intensity Tandem Bicycle Exercise Program on Clinical Severity, Functional Magnetic Resonance Imaging, and Plasma Biomarkers in Parkinson’s Disease. Front Neurol. 2020;11: 656. pmid:32793096
- 62. Shulman LM, Katzel LI, Ivey FM, Sorkin JD, Favors K, Anderson KE, et al. Randomized clinical trial of 3 types of physical exercise for patients with Parkinson disease. JAMA Neurol. 2013;70: 183–190. pmid:23128427
- 63. Tollár J, Nagy F, Kovács N, Hortobágyi T. Two-Year Agility Maintenance Training Slows the Progression of Parkinsonian Symptoms. Med Sci Sports Exerc. 2019;51: 237–245. pmid:30303934
- 64. Tollár J, Nagy F, Hortobágyi T. Vastly different exercise programs similarly improve parkinsonian symptoms: a randomized clinical trial. Gerontology. 2019;65: 120–127. pmid:30368495
- 65. Borg G. Borg’s perceived exertion and pain scales. Human kinetics; 1998.
- 66. Souza MF da S, Bacha JMR, Silva KG da, Freitas TB de, Torriani-Pasin C, Pompeu JE. Effects of virtual rehabilitation on cognition and quality of life of patients with Parkinson’s disease. Fisioterapia em Movimento. 2018;31.
- 67. Hagell P, Nygren C. The 39 item Parkinson’s disease questionnaire (PDQ-39) revisited: implications for evidence based medicine. Journal of Neurology, Neurosurgery & Psychiatry. 2007;78: 1191–1198. pmid:17442762
- 68. Crotty GF, Schwarzschild MA. Chasing protection in Parkinson’s disease: does exercise reduce risk and progression? Frontiers in Aging Neuroscience. 2020;12: 186. pmid:32636740
- 69. Lima LP, Leite HR, Matos MA de, Neves CDC, Lage VK da S, Silva GP da, et al. Cardiorespiratory fitness assessment and prediction of peak oxygen consumption by Incremental Shuttle Walking Test in healthy women. PLoS One. 2019;14: e0211327. pmid:30730949
- 70. Jin X, Wang L, Liu S, Zhu L, Loprinzi PD, Fan X. The impact of mind-body exercises on motor function, depressive symptoms, and quality of life in Parkinson’s disease: a systematic review and meta-analysis. International journal of environmental research and public health. 2020;17: 31.
- 71. Peyré-Tartaruga LA, Martinez FG, Zanardi APJ, Casal MZ, Donida RG, Delabary MS, et al. Samba, deep water, and poles: a framework for exercise prescription in Parkinson’s disease. Sport sciences for health. 2022;18: 1119–1127. pmid:35194464
- 72. Choi H, Cho K-H, Jin C, Lee J, Kim T-H, Jung W-S, et al. Exercise therapies for Parkinson’s disease: a systematic review and meta-analysis. Parkinson’s Disease. 2020;2020. pmid:32963753
- 73. Penko AL, Zimmerman NM, Crawford M, Linder SM, Alberts JL. Effect of aerobic exercise on cardiopulmonary responses and predictors of change in individuals with Parkinson’s disease. Archives of Physical Medicine and Rehabilitation. 2021;102: 925–931. pmid:33453190
- 74. Ivey FM, Katzel LI, Sorkin JD, Macko RF, Shulman LM. The Unified Parkinson’s Disease Rating Scale as a predictor of peak aerobic capacity and ambulatory function. Journal of rehabilitation research and development. 2012;49: 1269. pmid:23341319
- 75. Demonceau M, Maquet D, Jidovtseff B, Françoise A, DONNEAU TB, Croisier J-L, et al. Effects of 12 weeks of aerobic or strength training in addition to standard care in Parkinson’s disease: a controlled study. Eur J Phys Rehabil Med. 2017;53: 184–200.
- 76. Wu P-L, Lee M, Huang T-T. Effectiveness of physical activity on patients with depression and Parkinson’s disease: A systematic review. PloS one. 2017;12: e0181515. pmid:28749970
- 77. Pinto C, Salazar AP, Marchese RR, Stein C, Pagnussat AS. The effects of hydrotherapy on balance, functional mobility, motor status, and quality of life in patients with Parkinson disease: a systematic review and meta‐analysis. PM&R. 2019;11: 278–291. pmid:30884205
- 78. Landers MR, Navalta JW, Murtishaw AS, Kinney JW, Pirio Richardson S. 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: JNPT. 2019;43: 12–25. pmid:30531382
- 79. Lim S, Lang AE. The nonmotor symptoms of Parkinson’s disease—an overview. Movement Disorders. 2010;25: S123–S130. pmid:20187234
- 80. Merola A, Romagnolo A, Rosso M, Suri R, Berndt Z, Maule S, et al. Autonomic dysfunction in Parkinson’s disease: a prospective cohort study. Movement Disorders. 2018;33: 391–397. pmid:29278286
- 81. Rahmani F, Saghazadeh A, Rahmani M, Teixeira AL, Rezaei N, Aghamollaii V, et al. Plasma levels of brain-derived neurotrophic factor in patients with Parkinson disease: a systematic review and meta-analysis. Brain research. 2019;1704: 127–136. pmid:30296429
- 82. Palasz E, Niewiadomski W, Gasiorowska A, Mietelska-Porowska A, Niewiadomska G. Neuroplasticity and neuroprotective effect of treadmill training in the chronic mouse model of Parkinson’s disease. Neural Plasticity. 2019;2019. pmid:31073303
- 83. Prasad S, Holla VV, Neeraja K, Surisetti BK, Kamble N, Yadav R, et al. Parkinson’s Disease and COVID-19: Perceptions and Implications in Patients and Caregivers. Movement disorders: official journal of the Movement Disorder Society. 2020;35: 912–914. pmid:32304118
- 84. Haas AN, Passos-Monteiro E, Delabary MDS, Moratelli J, Schuch FB, Corrêa CL, et al. Association between mental health and physical activity levels in people with Parkinson’s disease during the COVID-19 pandemic: an observational cross-sectional survey in Brazil. Sport sciences for health. 2022;18: 871–877. pmid:35043063