The efficacy of High Intensity Interval Training (HIIT) versus aerobic exercise in the early stage of Parkinson’s Disease: A Systematic Review

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This study aimed to evaluate the efficacy of High-intensity interval training (HIIT) versus aerobic training in motor and non-motor symptoms in PD. Materials and Methods A literature search was performed since February 2024 to July 2025 in MEDLINE, EMBASE, Discovery @Bolton, PsycINFO, Google Scholar, PubMed, CINAHL, and SPORTDiscus. Data extracted by a single reviewer and cross checked by another. The risk of bias was assessed using the Revised Cochrane risk of bias tool, and quality of reporting was assessed using the Template for Intervention Description and Replication (TiDieR) checklist. Results The search yielded 9 studies involving a total of 263 people with PD in the early stages. The results from the risk of bias showed that 88.8% of studies were judged to be of moderate to high quality. The completeness of intervention reporting showed overall moderate (66.1%) quality of reporting. Conclusion HIIT showed improvement in physiological, cognitive, and overall quality of life (QoL) outcomes when compared to aerobic exercise. HIIT also showed significant improvement in cognitive function. PROSPERO Registration Number: CRD42023478541, 02 November 2023. " } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/14-1273", "name": "The efficacy of High Intensity Interval Training (HIIT) versus aerobic..." } } ] } Home Browse The efficacy of High Intensity Interval Training (HIIT) versus aerobic... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article El Hantari SEK and Nomikos PA. The efficacy of High Intensity Interval Training (HIIT) versus aerobic exercise in the early stage of Parkinson’s Disease: A Systematic Review [version 1; peer review: 1 approved with reservations, 1 not approved] . F1000Research 2025, 14 :1273 ( https://doi.org/10.12688/f1000research.170035.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Systematic Review The efficacy of High Intensity Interval Training (HIIT) versus aerobic exercise in the early stage of Parkinson’s Disease: A Systematic Review [version 1; peer review: 1 approved with reservations, 1 not approved] Soufiane El Kichouhi El Hantari https://orcid.org/0009-0004-4611-6997 1 , Polykarpos Angelos Nomikos https://orcid.org/0000-0001-6827-4938 1 Soufiane El Kichouhi El Hantari https://orcid.org/0009-0004-4611-6997 1 , Polykarpos Angelos Nomikos https://orcid.org/0000-0001-6827-4938 1 PUBLISHED 18 Nov 2025 Author details Author details 1 School of Clinical and Biomedical Sciences, University of Bolton, Bolton, England, BL3 5AB, UK Soufiane El Kichouhi El Hantari Roles: Conceptualization, Formal Analysis, Investigation, Methodology, Validation, Writing – Original Draft Preparation, Writing – Review & Editing Polykarpos Angelos Nomikos Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Project Administration, Supervision, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS Abstract Purpose Exercise is shown to be effective in Parkinson’s Disease (PD), but there is still controversy over which type of exercise is most effective. This study aimed to evaluate the efficacy of High-intensity interval training (HIIT) versus aerobic training in motor and non-motor symptoms in PD. Materials and Methods A literature search was performed since February 2024 to July 2025 in MEDLINE, EMBASE, Discovery @Bolton, PsycINFO, Google Scholar, PubMed, CINAHL, and SPORTDiscus. Data extracted by a single reviewer and cross checked by another. The risk of bias was assessed using the Revised Cochrane risk of bias tool, and quality of reporting was assessed using the Template for Intervention Description and Replication (TiDieR) checklist. Results The search yielded 9 studies involving a total of 263 people with PD in the early stages. The results from the risk of bias showed that 88.8% of studies were judged to be of moderate to high quality. The completeness of intervention reporting showed overall moderate (66.1%) quality of reporting. Conclusion HIIT showed improvement in physiological, cognitive, and overall quality of life (QoL) outcomes when compared to aerobic exercise. HIIT also showed significant improvement in cognitive function. PROSPERO Registration Number : CRD42023478541, 02 November 2023. READ ALL READ LESS Keywords Neurology, Parkinson’s Disease, High-Intensity Interval Training, Moderate-intensity Continuous Training, Usual Care. Corresponding Author(s) Polykarpos Angelos Nomikos ( [email protected] ) Close Corresponding author: Polykarpos Angelos Nomikos Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2025 El Hantari SEK and Nomikos PA. 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 work is properly cited. How to cite: El Hantari SEK and Nomikos PA. The efficacy of High Intensity Interval Training (HIIT) versus aerobic exercise in the early stage of Parkinson’s Disease: A Systematic Review [version 1; peer review: 1 approved with reservations, 1 not approved] . F1000Research 2025, 14 :1273 ( https://doi.org/10.12688/f1000research.170035.1 ) First published: 18 Nov 2025, 14 :1273 ( https://doi.org/10.12688/f1000research.170035.1 ) Latest published: 18 Nov 2025, 14 :1273 ( https://doi.org/10.12688/f1000research.170035.1 ) Introduction Parkinson’s Disease (PD) is a neurodegenerative condition caused by a decrease in dopaminergic neurons in the Substantial Nigra Pars Compacta (SNpc) and reduced dopamine levels in the basal nuclei. 1 The prevalence rate of PD is growing faster than any other condition 2 and is expected to double by 2030. 3 The loss of dopamine in the Substantial Nigra (SN) may contribute to neuroinflammation, increasing oxidative stress, leading to intrinsic destruction of the neurons. 4 These processes are interconnected; therefore, it is difficult to identify which pathological changes are responsible for the disease. 5 The aetiology of PD evolves from a complex interaction of genetic, environmental, and ageing risk factors. 6 PD is characterized by subtle non-motor symptoms such as sleep disturbances, mood disorders, depression, anxiety, urinary dysfunction, orthostatic hypotension, excessive daytime sleepiness, cognitive impairment, fatigue, and pain. 7 As PD progresses, motor symptoms, may affect one side of the body, and gradually extend to the other side. These cardinal motor symptoms include resting tremors, bradykinesia, rigidity, gait dysfunction, and postural instability. 8 The Hoehn and Yahr scale uses these symptoms to stage the severity of the disease. 9 Pharmacological management, engagement in physical activity, and lifestyle changes are the main approaches advocated for people with PD. Anti-parkinsonism medications such as dopamine replacement and dopamine agonists are administered as first-choice treatment in PD management. 10 Long-term use of anti-parkinsonism medications may lead to adverse effects (AE) such as wearing off, peak-dose dyskinesia and on-off phenomenon. 11 The role of neurorehabilitation as part of management of PD has significantly increased due to developments within the process of neuroplasticity. Potential neurorestorative effects of exercise in PD have been explored with promising outcomes if introduced in the early stage of the disease. 1 Exercise activates the central and peripheral nervous system and improves motor and non-motor symptoms. 12 Those have been associated with production of neuroprotective factors that optimize antioxidant mechanisms, thus slowing down the progression of PD. 13 Aerobic training is a physical activity aimed at increasing HR and oxygen consumption. Aerobic training enhances neuroplastic changes (angiogenesis, neurogenesis, synaptogenesis), 1 strengthens synaptic force and improves neural networks. 14 American Physical Therapy Association (APTA) 15 suggests that moderate to high intensity aerobic exercises should be implemented to reduce motor disease severity and improve functional outcomes in people with PD in the stages 1-3 of the Hoehn and Yahr scale. High Intensity Interval Training (HIIT) is an anaerobic type of exercise that reduces the risk of PD and slows down its progression. HIIT incorporates bouts of high-intensity/vigorous training with short rest or low-intensity periods in between. 16 O’Callaghan et al. 12 measured changes in brain-derived neurotrophic factor (BDNF) at the start and the end of 12 weeks. BDNF levels did not rise significantly from the start to the end of individual sessions. Over 12 weeks, BDNF levels significantly increased in the HIIT group but not in the Moderate Intensity Continuous Training (MICT) group or the control group. Kim et al. 17 suggested that HIIT significantly improves various sarcopenia-related parameters, such as lean mass, skeletal muscle mass, and functional performance measures, more than moderate-intensity continuous training (MICT) and control group. Ergun Y. et al. 18 compared aerobic fitness and HIIT on PD over 6 weeks. The authors found improved aerobic fitness (VO2max), motor function, fatigue, mood, executive function, and quality of life, while most cognitive measures remained unchanged. Motor Unified Parkinson’s Disease Rating Scale UPDRS scores were correlated with improved cognitive performance, selective attention and quality of life (p < 0.05). Harvey et al. reported significant improvements (p = 0.02) in maximum heart rate (HRmax) and peak oxygen consumption (VO2max), when HIIT was compared to controls. Fernandes et al. 19 compared HIIT and MICT collecting outcomes on hemodynamic and functional characteristics in PD patients and found improved endothelial reactivity and various hemodynamic measures. Considering all the above we can safely state that engaging in exercises by people living with PD has a vital role in their rehabilitation 20 due to exercise-induced positive neuroplastic changes resulting from increased physical activity. The emerging evidence supports the benefits of aerobic and HIIT training in managing PD symptoms has shown that the comparative effectiveness of these exercise modalities remains to be determined, specifically in the early stage of PD. The absence of a systematic review comparing HIIT versus aerobic training creates uncertainty in clinical decision-making. Despite the growing interest in exercise, there is a need for evidence-based guidelines as there is a lack of consensus regarding the most effective type of exercise. 21 This systematic review aims to assess the efficacy of HIIT versus aerobic training in early-stage of PD, assess the quality of reporting of studies identified, summarise findings and provide any future research recommendations. Methodology Study reporting The reporting of this systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and checklist to evaluate the effects of interventions. 22 The review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO), registration number: CRD42023478541. Data sources and search strategy A comprehensive literature search was performed on MEDLINE, EMBASE, Discovery @Bolton, PsycINFO, Google Scholar, PubMed, CINAHL, and SPORTDiscus, from February 08, 2024, to April 08, 2025. Studies in English were considered. A search strategy included synonyms, vocabulary terms, text words from previous articles and Medical Subject Heading (MeSH) terms were used. A complete search strategy has been documented in an extended data repository. Eligibility of studies Types of studies included RCTs, including pilot, cluster, crossover, parallel studies, feasibility studies or quasi-experimental that explored the effects of HIIT versus aerobic/usual care in early-stage PD patients in all settings. Intervention(s) The main intervention is HIIT, which incorporates bouts of high-intensity/vigorous training with short rest or low-intensity periods in between. 23 Control groups was assigned to aerobic training, no treatment, waiting list, placebo, or any other pharmacological and non-pharmacological intervention. Population Animal studies were excluded, and a detailed inclusion and exclusion criteria are illustrated in Table 1 . Table 1. Reasons for exclusion in title, abstract and full-text screening. Study design Excluded case reports, case series, cohort studies, single-case study, cross-sectional studies, reviews Type of publication Excluded books, protocols, reviews, posters, or abstracts Language Excluded if not in full version English or Spanish Intervention Excluded any study that does not include HIIT for one intervention (Cardio, HIIT with weight, bodyweight, and full body HIIT with or without other pharmacological or non-pharmacological interventions). Eligibility criteria Excluded if meeting none of the following criteria: • Early-stage of PD - 1 to 3 according to the Hoehn and Yahr staging scale (Hoehn and Yahr, 1967). • Meeting the criteria of the International Parkinson and Movement Disorder Society (MDS) (Postuma et al., 2015). • Doctors’ diagnosis of PD. Population criteria Excluded if: • Late stage of PD (4-5 in Hoehn and Yahr scale) • <18 years • Experiencing any other comorbidities along PD Outcome(s) The primary outcome includes physiological change, alteration in biomarkers, motor function, physical function, non-motor function and psychological outcomes. Secondary outcomes are also used in most studies to measure physical function and physiological and psychological changes contributing to overall QoL. These outcomes were selected based on previous studies that provided similar outcome data. If outcome data are consistent, a meta-analysis would be feasible. Data collection Study identification Two reviewers (SEK and PAN) participated in the screening process. SEK initially screened the title and abstract using Covidence software. Then, PAN screened 10% independently and reached an overall agreement after a verbal discussion with SEK. This same process was used for full-text screening. Approach to data synthesis Data were synthesised using a descriptive synthesis of participant characteristics, study characteristics, and assessment. The findings of the included studies were organised and illustrated into tables and figures. A preliminary synthesis was used to summarise the findings. Then, a narrative synthesis was followed to bring the results together and draw conclusions. Data extraction and management The main reviewer (SEK) extracted data used Cochrane Data Collection tool for RCT. Another independent reviewer (PAN) reviewed and validated 10% of the data extracted from studies. Study quality appraisal Risk of bias The quality of the studies was assessed using a tool for RCTs Revised Cochrane Risk-of-Bias (RoB2). Each domain has a specific signalling question to assess relevant information related to the risk of bias. The answer can be “Low”, “High”, or “Some concerns”. The domains are: “Bias arising from the randomization”, Bias due to deviation from intended intervention, “Bias due to missing outcome data”, “Bias in measurement of the outcome”, “Bias in selection of the reported results”, and “Overall bias”. Two reviewers (SEK and PAN) participated in the screening process. PAN screened 10% independently and reached 100% overall agreement. Quality of reporting of interventions The Template for Intervention Description and Replication (TiDieR) checklist was used to assess the quality of reporting of the interventions. The outcomes for each intervention in each study were reported initially in separate tables using a 3-point Likert scale, not reported (0 = X), partially reported/unclear (1 = ?), and adequately reported (2 = ✓). Then, the results were combined for intervention 1, comparators and/or control group and created a summary score. Data was combined and reported using strategies from previous studies (see Table 2 ). Table 2. Instructions for reporting scores on two treatment groups (Yamato et al., 2018). Intervention group Control group Score Rating for each item No No 0 No N/A 0 Yes No 1 No Yes 1 Yes Yes 2 Yes N/A 2 Results Selection of studies A total of 327 studies were obtained from electronic databases and manual searches, of which 87 were duplicated and eliminated. Following duplicate removal, 238 studies were included in the title and abstract screening. There was 100% agreement with the independent reviewer (PAN) on study selection. From 238 studies, 206 were excluded, and 32 citations were moved to full-text screening, of which 23 were excluded for different reasons: not peer reviewed (1), wrong intervention (16) and wrong study design (6). A final number of 9 studies were included in the final analysis (see Figure 1 ). Figure 1. Prisma flow diagram. Study characteristics Studies considered and identified were published in the last eleven years (from 2015 to 2025). These studies were conducted in the United Kingdom, Canada, America (USA and Brazil) and South Korea. Studies identified were conducted in different settings: one study was delivered in a community setting, four studies were delivered in a university setting, one was in a secondary care, one was in a primary setting, one home-based and one on single centre setting. All studies gained ethical approval. These studies reported the eligibility criteria for the population considered for inclusion. All nine studies used the Hoehn and Yahr scale criteria 9 for PD. Five studies had two arms (HIIT and Aerobic or Control group), and four studies had three arms (HIIT, aerobic training and control group). Four were RCTs, one was a randomised pilot study, one was a crossover trial, one was a parallel single-blinded trial, and two feasibility trials. Study and intervention characteristics In total, 263 participants were included in the study. Of 263 participants, 229 (87.07%) completed the study and 34 (12.92%) dropouts. The mean percentage of females was 37.34%. The mean age was 67.31 years across all nine studies. Two studies did not report the mean duration of the disease; however, the mean duration of the disease was 5.26 years across the other seven studies that reported this data. The mean range of the Hoehn and Yahr scale across all nine studies was early-stage 1-3. Further details of participants’ characteristics are illustrated in Table 3 , details of intervention characteristics are shown in Table 4 and assessment and outcome data are presented in Table 5 . Clinical variability and significant heterogeneity are found among the collected outcomes and its measures. Table 3. Participant and study characteristics. Author (year) Country Study design Sample size (N), (intervention, intervention 2/Control) Mean age (years) Number (Completers, Dropouts) Gender (male%, female%) Hoehn and Yahr stage (range) Mean duration of disease Ergun Y. et al., (2014) USA 2 x 2 RCT N = 60 (38, 22) 65.4 (49, 11) (68.3%, 31.7%) Early – Mid (1 – 3) 5.5 years Kim et al., (2023) South Korea Randomized pilot trial N = 33 (11, 11, 11) 66.17 (30, 3) (49.73%, 50.27%) Early - (1 – 2) 2.5 years Fernandes et al., (2021) Brazil Randomized, cross-over, and controlled study N = 12 (Not reported) 66.2 (12, 0) (50%, 50%) Early – Mid (1 – 3) 5.75 years Fiorelli et al., (2018) Brazil RCT N = 14 (Nor reported) 66.50 (14, 2) (50%, 50%) Early – Mid (1 – 3) 5.70 years O’Callaghan et al., (2020) United Kingdom RCT MICT N = 32 (16, 16) HIIT N = 20 (10, 10) MICT = 67.5 HIIT = 68.9 MICT (27, 5) HIIT (17, 3) MICT (63.15%, 36.85%) HIIT (52.8%, 47.2%) Early – Mid (1 – 3) Not reported Fernandes et al., (2020) Brazil Randomized parallel (2 interventions), single-blinded trial N = 27 (13, 14) 68.6 (21, 6) (61.90%, 38.09%) Early - Mid (1 – 3) 5.75 years Harvey et al., (2019) United Kingdom Randomized, controlled, feasibility study with waiting list control N = 20 (10,10) 68.5 (17, 3) (60%, 40%) Early - Mid (1 – 3) Not reported Kathia et al., (2024) Canada RCT N = 29 (15, 13) Not reported (29, Not reported) MICT (64%, 36%) HIIT (60%, 40%) Early - Mid (1 – 3) 5.6 years Harpham et al., (2025) United Kingdom Randomized, controlled, feasibility trial N = 14 (7, 7) 68 HIIT (6, 1) Control (7, 0) Control (86%, 14%) HIIT (86%, 14%) Early – Mid (1 – 2) 6 years Table 4. Intervention characteristics. Study Exercise type Intervention Intensity, Duration (min), Frequency (times/week) Comparator/Control Intensity, Duration (min), Frequency (times/week) Duration of study Health Care Professional (HCP) Ergun Y. et al., (2014) Aerobic exercises programme HIIT: (80%-90% HRmax) 15-45 min 3x/wk. Continuous/ moderate intensity : (70%-80% HRmax) 15-45 min 3x/wk. 6-months Exercises trainers Kim et al., (2023) Cycle ergometer & calisthenics HIIT: 60% VO2max for 30–50s with 1-min rest Intervals, 40-60 min, 3x/wk. MICT: 50% VO2max, 40 – 60 min, 3x/wk. CON: Normal daily activities. 24-weeks Not reported Fernandes et al., (2021) Cycle ergometer HIIE: (4 min of warm-up, 21 min alternating 1 min at levels 15-17 with 2 min at levels 9-11 of rating of perceived exertion [RPE]). Total 25 min MICE: (4 min of warm-up followed by 26 min at levels 11-14 of RPE). 30 min CON: 30 min of sitting rest 14 days Observer Fiorelli et al., (2018) Stationary bicycle HIIT: 4 min warm-up at 9 to 11 RPE, 21 min high-intensity intervals at 15 to 17 RPE (1 min) alternated with moderate-intensity intervals at 9 to 11 RPE (2 min). Total 25 min MICT: 4 min warm-up at 9 to 11 RPE, 26 min moderate Intensity exercise at 11 to 13 RPE. Total 30 min CON : 30 min of seated resting. 17 days Physiotherapist O’Callaghan et al., (2020) MICT: Aerobic and resistance training (treadmill walking/running, sit-to-stand, marching, step ups, hand cycling, recumbent cycling and boxing. HIIT: The Speedflex machine. HIIT: ≥ 85% HRmax, 10-min warm-up, 4-min HIIT, with 3.5 min rest, 4 exercises at 45 s and recovery of 15 s. 5 min cool down. Total: 16 min raising to 24 (by week 12). Frequency: 3x/wk. CON: Usual care MICT: 60–80% HRmax, 10-min warm-up and cool down, aerobic stations were 6 x 4min (24min), and resistance stations were 6 x 2 min (12 min). Total 36 min. 3x/wk. CON: Usual care 12 weeks Researchers, exercise trainer, Research nurse, exercise physiologist, physician, and physiotherapist Fernandes et al., (2020) Walking, and jogging/running. HIIT: 4 min warm-up (walking at 9 level of RPE), followed by 21min alternating 1min of jogging/running at 15 to17 level with 2min of walking at 9 to 11 level of RPE. Frequency: 3x/wk. MICT: 4 min of warm-up (walking at 9 level), followed by 26 min of walking/jogging at 11 to 14 level of RPE. Frequency: 3x/wk. 12 weeks Exercise specialist Harvey et al., (2019) Exercise circuit whole-body movements (e.g. power clean and press, step and press, squat, pulldown to squat, high pull and bent over row). Double-concentric, variable resistance Speedflex machines. HIIT: ≥85% HRmax, 10-min warm-up, 4-min HIIT, with 3.5 min rest, 4 exercises at 45 s and recovery of 15 s. 5 min cool down. 45-60 min per session. Frequency: 3x/wk. CON: Usual lifestyle and physical activity habits. 12 weeks Research nurses, senior physiotherapist, a senior research associate and a doctor Kathia et al., (2024) HIIT – Cycling HIIT: 80-85% HRmax performed on a cycle ergometer; sessions 30 min approx. (incl. intervals & warm-ups/cool-down); 3 times a week MICT: Cycling 60-65% HRmax, 30 min approx. continuous. 3 times week. 10 weeks Physiologists Harpham et al., (2025) Home-based HIIT – Walking 75-90% HRmax 25-30 min per session; 3x/week Usual care (no structured exercises intervention) 12 weeks Remote support by physiotherapists and exercises professionals Table 5. Assessment and outcome data. Study Time points (weeks) Outcome (Measures) Results Ergun Y. et al., (2014) 6 weeks Primary: Aerobic fitness, cognition, and parkinsonism (UPDRS) Secondary: Quality of life (FSS, Geriatric Depression Scale, and PDQUALIF). Observed improvements in aerobic fitness (maximum oxygen consumption), motor function, fatigue, mood, and aspects of executive functions and quality of life. No significant changes on most cognitive measures. Improvement in motor UPDRS score across all completers. Increase in VO2max correlated with improvement on the flanker task and quality of life (p < 0.05). Kim et al., (2023) 24 weeks Primary: Efficacy on sarcopenia-related parameters and physical performance (Appendicular skeletal muscle mass, hand dynamometer, 6-min walking test and the 30-s chair-stand test) Overall, 75% patient that underwent HIIT showed an improvement in sarcopenia after the 24-week intervention, however, no improvement in sarcopenia showed in MICT and control group patients. HIIT group reported increased in lean mass (p = 0.011), Appendicular skeletal muscle mass (ASM) (p = 0.035), and ASM index (p = 0.025). Good improvement in 6-min walk test (p = 0.024) and 30s chair-stand test (30CST) compared with control group whereas MICT showed a good improvement just in 30cst compared to control group (p = 0.002). Fernandes et al., (2021) Before, immediately after and 45min after each intervention Primary: Hemodynamic and cardiac autonomic response parameters (blood pressure, HR, endothelial reactivity, and HR variability). There were significant, but small increase between HIIE and MICE (P<0.01) in Heart rate and systolic Blood Pressure at post HIIE and MICE. No significant difference in diastolic Blood Pressure, endothelial reactivity, and Heart rate variability (HRV). Overall, study reported hemodynamic and cardiac autonomic response is impaired in PD but not difference between both interventions. Fiorelli et al., (2018) Week 1 Week 2 Week 3 Before and after each intervention Primary: Cognition function i.e. associated verbal pairs, symbol search, digit span, attention, memory, processing speed, executive functions and visuomotor skills (Wechsler Adult Intelligence Scale-III, and trail making test) Acute bout of HIIT showed an improvement in auditory memory (p < .02), attention (P < .001) and sustained attention (P < .01), whereas MICT improved immediate auditory memory (P < .01) and no effects on cognitive function on the control group. However, working memory (cognitive function affected at early stage of PD and dependant of dopaminergic system) did not improve after both exercises session. O’Callaghan et al., (2020) Intervention group: Before, and immediately after, the first and last exercise sessions. Control group: Week 1 & 12 Primary: Exercise intensity on BDNF levels in people with PD (Emax Immuno Assay system and Bio-Rad Benchmark micro plate reader). Secondary: Cognition (Montreal Cognitive Assessment), peak oxygen uptake (VO2max) and blood samples. Not significant rise in BDNF level immediately from the start to end of each session. However, across the 12-week study (long-term), BDNF rise significantly in HIIT, but not in MICT and Control group. Fernandes et al., (2020) Week 1 & 12 Primary: Hemodynamic changes after intervention (Resting BP and heart rate, arterial stiffness, endothelial, reactivity and HRV) Secondary: Functional adaptation ( 5-timesit-to-stand (STS), timed up and go and 6-minute walking tests) Increased endothelial reactivity in HIIT (∼8%, P < .01) but not after MICE during follow-up. Six-minute walk test improved after HIIT (10.4 ± 3.8%, P < .05), but not after MICE. Sit to stand improved in HIIT (27.2 ± 6.1%, P < .05) and MICE (21.5 ± 5.4%, P < .05). Overall, HIIT was superior to MICE on improving endothelial reactivity and aerobic capacity in PD. Harvey et al., (2019) Weeks 13-14 Weeks 27-28 Weeks 18-19 Weeks 32-33 Primary: Feasibility of HIIT ⩾85% HRmax, session attendance, drop-out, heart rate and adverse events. Secondary: Functional assessment (6-minute walk test, MoCA, and 39-item Parkinson’s Disease Questionnaire). Cardiorespiratory function: VO2max, cardiac function and cardiac output (Quark Cardiopulmonary Exercise testing system, ECG and CHEETAH NICOM system). There was significant increase of 0.23% (p = 0.019) per week in mean HR peak as a percentage of HR max across the intervention period. HIIT showed a significant improvement in VO2peak pre to post intervention that was maintained at six-week follow-up in comparison to the control group. Non-significant improvement in cognition and gait speed in HIIT compared to Control group. Kathia et al., (2024) Week 1 Week 10 VO2max & UPDRS-III There was an increased in both groups (P 0.09). Knee extensor strength significantly increased over time (P = 0.03) Harpham et al., (2024) Week 1 Week 12 Feasibility – Completion, adherence, fidelity and adverse events. UPDRS-III Completion: 6/7 HIIT participants completed; 1 dropout (back injury) Adherence: 78.4% sessions Adverse events minimal BDNF, VO2max, UPDRS-III – No significance over control group Quality of the studies Overall, four studies (44.4%) had a low risk of bias, indicating high-quality studies. 16 , 17 , 24 , 25 One (11.1%) study 26 presented a high risk of bias. Four studies (44.4%) had some concerns across the risk of bias domains. In domain 1, the plot indicated that 55.5% of studies had no bias from the randomisation process. The remaining 44.5% of studies presented some concerns regarding the method used for randomisation. In domain 2, 100% of studies indicated a high risk of bias due to the blinding process and the nature of the intervention. Domain 3, showed that all (100%) studies had a low risk of bias regarding any missing outcome data. Domain 4 presented six studies (66.6%) with a low risk of bias, one (11.1%) study 26 had some concerns regarding the measures utilized to assess outcomes at comparable times between intervention groups and two (22.2%) studies reported high risk of bias. Domain 5 indicated a high risk of bias in six studies (66.6%) aroused through the reporting of result which means they did not report analysis of intention/intention to treat and two (22.2%) studies 16 , 25 reported intention to treat (see Figure 2 ). Figure 2. Traffic light plot of risk of bias. Quality of reporting of the trials Intervention condition reported higher completeness (42%) compared to the comparator (36%) and control group (22%). Exceptional quality of reporting (>90) was observed for items 1 (intervention name), 2 (intervention rationale), 4 (intervention procedures) and 8 (when and how much) within the intervention group. In contrast, intervention 2/comparator demonstrated moderate scores for these items. Moderate scores (>50%) were consistent across items 3 (materials), 6 (how), and 7 (intervention location) for all groups. However, information about items 5 (who provided intervention), 9 (tailoring of intervention), 11 (how intervention fidelity was assessed), and 12 (actual intervention fidelity) had poor-quality reporting (50%), and only one study 16 reporting low quality (<50%). Adverse effects (AE) Most studies reported minor exercises-related AEs, such as knee or hip pain, fatigue, and muscle soreness, typically during HIIT. No serious AEs were noted in any study, and symptoms were generally transient or manageable. Discussion This systematic review assessed the efficacy of HIIT versus aerobic exercises or control group in the early stage of PD. We also assessed the quality of reporting of the RCTs that were eligible for inclusion. The efficacy of HIIT over aerobic training or control group with usual care showed improvements in aerobic capacity, motor function, sarcopenia-related parameters, cognitive function, and Brain-Derived Neurotrophic Factor (BDNF) levels at different time points. Therefore, these results may be associated with the overall efficacy of this intervention over time. A recent systematic review and meta-analysis 14 aimed to assess the feasibility, safety, and clinical effects of HIIT in PD. The authors identified eleven studies and found that HIIT may be a safe and feasible option for people with PD, those with mild to moderate disease severity. This is in line with our findings. However, this study did not include participants in a specific stage of the disease and included any study design considering any modality of HIIT. The RCT conducted by Ergun et al. 18 observed that HIIT improved aerobic fitness, motor function, fatigue, mood, and overall QoL. There was statistical significance (p < 0.05) on increasing VO2 max, QoL and improvement in the Unified Parkinson’s Disease Rating Scale (UPDRS) score across all participants. Similarly, another RCT conducted by O’Callaghan et al. 12 found that BDNF levels increased significantly in the long term across a 12-week study, but changes were absent in the MICT and control group. The reduction in neuroinflammation biomarkers caused by increased BDNF levels has been highlighted as an important therapeutic strategy for PD. 28 This is in line with the study from Harpham et al. 14 that found HIIT improved cardiorespiratory fitness and may increase BDNF levels. Similarly to the previous two studies, Kathia et al. 25 found that both HIIT and MICT significantly increased VO2peak during the study (p < 0.01). However, the improvement was better in the HIIT group (∼3.7 ± 3.7 ml/kg-1/min-1) than MICT (∼1.7 ± 3.2). UPDRS-III symptoms showed statistical improvement (P < 0.001) equally in both groups. This suggesting that HIIT may provide greater cardiovascular benefits which can be clinically important. Furthermore, the RCT conducted by Fernandes et al. 19 found increase in endothelial reactivity in HIIT (∼8%, P < .01) and aerobic capacity but not in the MICE group after follow-up. Also, this study reported overall increase in sit to stand test for both HIIT (27.2 ± 6.1%, P < .05) and MICE (21.5 ± 5.4%, P < .05). HIIT showed a better outcome in the six-minute walk test (10.4 ± 3.8%, P < .05), but not after MICE. However, a RCT conducted by Fernandes et al. 24 found an increase in HR and systolic blood pressure, with a small statistical significance between HIIE and MICE (P < 0.01) reported. This study had a small sample size (12 participants), and the duration of the study (14 days) was small, compared to the study conducted by Fernandes et al., 19 which used a similar intervention regime. Therefore, this could influence the detection of true effects and extrapolation of data into clinical settings. Also, the study conducted by Fernandes et al. 19 used a single-blinded design, which can lead to the ascertainment of outcomes and increase the risk of co-intervention. The allocation concealment was affected, leading to exaggerated estimates of treatment effects. Moreover, a RCT conducted by Kim et al. 17 not only indicated that HIIT was superior (p = 0.024) to MICT and the control group in improving the 6-min walk test but also indicated improvement in sarcopenia-related parameters [Lean mass (p = 0.011), Appendicular skeletal muscle mass (ASM) (p = 0.035), and ASM index (p = 0.025)] after 24-week intervention. In addition, Harvey et al., found that HIIT showed a significant improvement of 0.23% (p = 0.019) per week in mean HRpeak across the intervention period, as well as a significant increase in VO2peak pre and post intervention that was maintained at six-week follow-up in comparison to the control group. Similarly, the meta-analysis conducted by Harpham et al., 14 which explored the pooled effects of HIIT on VO2 max, revealed a significant improvement in HIIT compared to usual care. However, significant improvement in HIIT was not only observed in physiological and functional parameters but also in cognitive functions. Fiorelli et al. 26 found that an acute bout of HIIT showed an improvement in auditory memory (p < .02), attention (P < .001) and sustained attention (P < .01), whereas MICT improved immediate auditory memory (P < .01) and no effects on cognitive function on the control group. Feasibility and adherence also was assessed by Harpham et al. 27 and found 78.4% adherence rate to the HIIT sessions where only one participant withdrew due to a non-intervention-related back injury and no serious adverse events reported. Exercises intensity was achieved during HIIT (77.2% HRmax) however, 3 of 7 participants did not consistently achieved threshold intensity of ≥75% HRmax, which raises concerns regarding intensity fidelity in unsupervised settings. Overall, the changes in different physiological and psychological parameters of these nine RCTs indicated that the effects of HIIT were depicted as a long-term effect. Therefore, it is conceivable that a correlation between intensity and dose-response exists. Although the significant effects of HIIT versus aerobic or control group were transparent, the risk of bias identified potential systematic errors or deviation from the truth in the study, which can lead to misleading results. Across nine studies, only one study presented an overall high risk of bias, four studies presented a low risk of bias, and four studies presented some concerns. However, although the overall risk presented as high-quality papers, all studies presented high-risk bias due to the inadequate blinding and concealment allocation process due to the nature of the intervention. This can lead to exaggerated treatment effects, affecting the validity and reliability of findings. Also, 66.67% of studies 12 , 17 , 19 , 24 , 26 indicated bias arousing through the reporting of results as these studies did not report intention to treat. This finding suggests that some studies did not include all participants in their analyses, potentially leading to misleading conclusions due to the exclusion of dropouts and protocol deviations. This can affect the validity and generalizability of the conclusions drawn from the studies. 29 The completeness of intervention reporting demonstrated variability across groups. Completeness of the intervention reporting was more accurate in the intervention group (42%) compared to the comparator (36%) and control group (22%). Excellent quality of reporting was observed for the intervention name, rationale, procedures and when and how much in the intervention group and moderate in the comparator/control group. However, results indicate that there was poor-quality reporting of item 5 (who provided intervention), 9 (tailoring of intervention), 11 (how intervention fidelity was assessed) and 12 (actual intervention fidelity), which shows that the validity of studies is affected. The studies fail to provide level of expertise of the professionals delivering the interventions as well as details about specific training provision. Those imposes challenges when considering implementation of quoted interventions. In addition, there was poor reporting of how the intervention was planned to be tailored, titrated, or adapted to participants. Therefore, it is difficult to understand if the intervention was adapted to participants, thus affecting the replicability of the intervention in clinical settings. Moreover, fidelity was poorly reported across studies and interventions, which means that researchers may encounter difficulties in understanding how closely the intervention was delivered as intended. This affects the reliability of the study findings. 30 Lastly, the actual intervention fidelity was reported poorly, which indicates that the study may not have followed the intended intervention. If fidelity was affected during the intervention, this could impact the effectiveness of the intervention and affect future researchers’ ability to replicate the interventions provided accurately. 30 From the nine RCTs included, there were no serious AE. Seven studies reported minor musculoskeletal AE (knee pain, lower back pain, ankle pain and hip pain) and one participant experienced a drop in blood pressure during HIIT. This could be due to the impact of PD in the autonomic nervous system causing dysfunction such as neurogenic orthostatic hypotension (NOH), characterised by blood pressure drop upon standing causing symptoms such as dizziness, blurred vision, or fainting. 31 There were 8/65 participants who reported AE during HIIT, 7/77 participants in aerobic training and 0/48 participants in the control group. This indicated that more participants in HIIT reported exercise-related AE than those in aerobic training or the control group. However, it remains unclear whether these events resulted directly from HIIT. Overall, this showed a low AE across all interventions, suggesting minimal harmful effects and highlighting the safety and tolerability of interventions. Contribution and limitations This systematic review has some contribution and limitations. Firstly, this study provides new insight and exploration of the clinical trials available about the efficacy of HIIT versus aerobic exercises or usual care in early-stage PD. This study used a rigorous methodological approach to validate the findings. This systematic review included an independent reviewer to validate through the process of data extraction and selection studies, which reported a high level of agreement between both reviewers. This study has used a Cochrane RoB tool and not the Physiotherapy Evidence Database (PEDro), as RoB is encouraged for quality assessment trials. 32 Therefore, this study used robust methods to assess the quality of the studies. The results of this study have been shown to be reliable as the findings were consistent across the studies. In addition, this study included only RCTs as they are considered the gold standard for assessing treatment effectiveness. Therefore, this study provides reliable evidence on treatment outcomes. Nonetheless, several limitations must be acknowledged. Firstly, the number of studies and participants included in this review has been small. Sample size can affect the internal and external validity of the study. Also, this study focused on articles published in English and Spanish, which questions the applicability and generalizability to the wider population and other countries. Furthermore, no patients’ perspective was considered in this study. This means that measures may not fully represent patients’ priorities, such as QoL, emotional wellbeing, or ease of adherence to treatment. Excluding patient voices can be seen as treating patient as passive recipients of care rather than active participants in decisions that affects their lives. Also, findings that do not account for patients’ preferences, needs or challenges may impact its implementation in real-world settings, leading to lower rate of adoption or satisfaction. Therefore, it is essential to interpret the conclusion with caution. This systematic review presents the most comprehensive evidence of the efficacy of HIIT versus aerobic exercises or control group (usual care, GP care, placebo, waiting list) at improving physiological, psychological, and clinical parameters as well as overall QoL in the early stage of PD. However, future research should aim to progress to a meta-analysis to synthesise the evidence from these studies and expand into providing a quantitative assessment of intervention effectiveness. Additionally, larger studies are needed to improve generalizability and validity. Therefore, future research should aim to improve recruitment process to achieve larger sample sizes in their studies and therefore improve statistical power and reliability. Conclusion In this systematic review, we have provided comprehensive evidence regarding HIIT compared to aerobic exercises or control groups (usual care, GP care, placebo, waiting list) in improving different outcomes that contribute to improving QoL in the early stage of PD. These findings suggest that HIIT is a highly effective intervention compared to aerobic training or usual care. However, different styles of exercises exist offering different options to patient with a long-term condition. Considering patients preferences as well as services being able to provide the same style of exercises. Although this study showed the effectiveness of HIIT, however, it is essential to note the limitations of the studies included, and the bias aroused. Therefore, future research should focus on conducting a meta-analysis to synthesise evidence and provide a quantitative assessment of intervention effectiveness to guide future research and clinical practice. Data availability statement Underlying data The project contains the following underlying data: Figshare: [The efficacy of High Intensity Interval Training (HIIT) versus aerobic exercise in the early stage of Parkinson’s Disease: A Systematic Review]. This is the completed PRISMA checklist. https://doi.org/10.6084/m9.figshare.30120736 . The project contains the following underlying data: PRISMA_2020_checklist.docx. Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0). 33 , 34 Extended data This project contains the following extended data: Figshare: [The efficacy of High Intensity Interval Training (HIIT) versus aerobic exercise in the early stage of Parkinson’s Disease: A Systematic Review]. • Supplementary Material Search Strategy. This is the detailed search strategy conducted. https://doi.org/10.6084/m9.figshare.30108868 33 , 34 Acknowledgment We take this opportunity to thank Andre Myles Jones and Dr Anna Ziemer for reviewing and editing the manuscript. References 1. Xu X, Fu Z, Le W: Exercise and Parkinson’s disease. Int. Rev. Neurobiol. 2019; 147 : 45–74. Publisher Full Text 2. Kalia LV, Lang AE: Parkinson’s disease.2015; 386 : 896–912. 3. Aarsland D, Batzu L, Halliday GM, et al. : Parkinson disease-associated cognitive impairment. Nat. Rev. Dis. Primers. 2021; 7 : 47. Publisher Full Text 4. 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Kim R, Choi S, Kang N, et al. : Effects of high-intensity interval training and moderate-intensity continuous training on sarcopenia-related parameters in participants with Parkinson’s disease: A 24-week randomized pilot trial substudy. Parkinsonism Relat. Disord. 2023; 117 : 105901. PubMed Abstract | Publisher Full Text 18. Uc EY, Doerschug KC, Magnotta V, et al. : Phase I/II randomized trial of aerobic exercise in Parkinson disease in a community setting. Neurology. 2014; 83 : 413–425. PubMed Abstract | Publisher Full Text | Free Full Text 19. Fernandes B, Barbieri FA, Arthuso FZ, 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. PubMed Abstract | Publisher Full Text 20. LaHue SC, Comella CL, Tanner CM: The best medicine? The influence of physical activity and inactivity on Parkinson’s disease. Mov. Disord. 2016; 31 : 1444–1454. 21. Radder DL, Silva L, de Lima A , et al. : Physiotherapy in Parkinson’s disease: a meta-analysis of present treatment modalities. Neurorehabil. Neural Repair. 2020; 34 : 871–880. PubMed Abstract | Publisher Full Text | Free Full Text 22. Moher D, Liberati A, Tetzlaff J, et al. : Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009; 339. 23. Riebe D, Ehrman JK, Liguori G, et al. : ACSM’s guidelines for exercise testing and prescription. American College of Sports Medicine; 2018. 24. Fernandes B, Barbieri FA, Marcal IR, et al. : Hemodynamic response to exercise is impaired in individuals with Parkinson’s disease. J. Sports Med. Phys. Fitness. 2021; 62 : 389–394. 25. Kathia MM, Duplea S-G, Bommarito JC, et al. : High-intensity interval versus moderate-intensity continuous cycling training in Parkinson’s disease: a randomized trial. J. Appl. Physiol. 2024; 137 : 603–615. PubMed Abstract | Publisher Full Text 26. Fiorelli CM, Ciolac EG, Simieli L, 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. Publisher Full Text 27. Harpham C, Gunn H, Marsden J, et al. : Home-Based High-Intensity Interval Training for People With Parkinson’s: A Randomized, Controlled. Feasibility Trial. Health Science Reports. 2025; 8 : e71024. PubMed Abstract | Publisher Full Text | Free Full Text 28. Zoladz JA, Majerczak J, Zeligowska E, et al. : Moderate-intensity interval training increases serum brain-derived neurotrophic factor level and decreases inflammation in Parkinson’s disease patients. J. Physiol. Pharmacol. 2014; 65 : 441–448. PubMed Abstract 29. McCoy CE: Understanding the intention-to-treat principle in randomized controlled trials. West. J. Emerg. Med. 2017; 18 : 1075–1078. PubMed Abstract | Publisher Full Text | Free Full Text 30. Toomey E, Hardeman W, Hankonen N, et al. : Focusing on fidelity: narrative review and recommendations for improving intervention fidelity within trials of health behaviour change interventions. Health Psychol. Behav. Med. 2020; 8 : 132–151. PubMed Abstract | Publisher Full Text | Free Full Text 31. Tulbă D, Cozma L, Bălănescu P, et al. : Blood pressure patterns in patients with Parkinson’s disease: a systematic review. Journal of personalized medicine. 2021; 11 : 129. PubMed Abstract | Publisher Full Text | Free Full Text 32. Armijo-Olivo S, da Costa BR , Cummings GG, et al. : PEDro or Cochrane to assess the quality of clinical trials? A meta-epidemiological study. PloS one. 2015; 10 : e0132634. PubMed Abstract | Publisher Full Text | Free Full Text 33. Angelos Nomikos P, El Kichouhi El Hantari S: Supplementary material_search strategy.docx. Dataset. figshare. 2025. Publisher Full Text 34. Angelos Nomikos P, El Kichouhi El Hantari S: PRISMA_2020_checklist.docx. Dataset. figshare. 2025. Publisher Full Text Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 18 Nov 2025 ADD YOUR COMMENT Comment Author details Author details 1 School of Clinical and Biomedical Sciences, University of Bolton, Bolton, England, BL3 5AB, UK Soufiane El Kichouhi El Hantari Roles: Conceptualization, Formal Analysis, Investigation, Methodology, Validation, Writing – Original Draft Preparation, Writing – Review & Editing Polykarpos Angelos Nomikos Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Project Administration, Supervision, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (1) version 1 Published: 18 Nov 2025, 14:1273 https://doi.org/10.12688/f1000research.170035.1 Copyright © 2025 El Hantari SEK and Nomikos PA. 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 work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article El Hantari SEK and Nomikos PA. The efficacy of High Intensity Interval Training (HIIT) versus aerobic exercise in the early stage of Parkinson’s Disease: A Systematic Review [version 1; peer review: 1 approved with reservations, 1 not approved] . F1000Research 2025, 14 :1273 ( https://doi.org/10.12688/f1000research.170035.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 18 Nov 2025 Views 0 Cite How to cite this report: Roy B. Reviewer Report For: The efficacy of High Intensity Interval Training (HIIT) versus aerobic exercise in the early stage of Parkinson’s Disease: A Systematic Review [version 1; peer review: 1 approved with reservations, 1 not approved] . F1000Research 2025, 14 :1273 ( https://doi.org/10.5256/f1000research.187448.r438769 ) The direct URL for this report is: https://f1000research.com/articles/14-1273/v1#referee-response-438769 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 27 Dec 2025 Barnana Roy , Garden City University, Bengaluru, Karnataka, India Not Approved VIEWS 0 https://doi.org/10.5256/f1000research.187448.r438769 Reviewer’s Comments on Manuscript Dear Authors, I have carefully reviewed the manuscript titled “The efficacy of High Intensity Interval Training (HIIT) versus aerobic exercise in the early stage of Parkinson’s Disease: A Systematic Review”. The manuscript addresses ... Continue reading READ ALL Reviewer’s Comments on Manuscript Dear Authors, I have carefully reviewed the manuscript titled “The efficacy of High Intensity Interval Training (HIIT) versus aerobic exercise in the early stage of Parkinson’s Disease: A Systematic Review”. The manuscript addresses an important and clinically relevant question by comparing the efficacy of high-intensity interval training (HIIT) and aerobic exercise in individuals with early-stage Parkinson’s disease. However, several aspects of the manuscript require clarification and strengthening to improve scientific rigor, transparency, and alignment with systematic review standards. We believe that addressing these issues will substantially enhance the clarity and scientific rigor of this manuscript. Below, I outline the comments for each section (Introduction, Methodology, Results). Introduction: In the section discussing pharmacological management and neurorehabilitation (starting with "Pharmacological management, engagement in physical activity..."), the authors may wish to incorporate a reference to "Recent Trends in Physical Therapy Interventions and Neuromodulation Techniques to Improve Neurorehabilitation." (P Nath et.al., 2025). Integrating this article would provide a smoother transition from standard medical management to the specific discussion on exercise-induced neuroplasticity by highlighting emerging trends in physical therapy and neuromodulation. Contradiction in Cognitive Findings: One sentence states, "The authors found improved... executive function... while most cognitive measures remained unchanged." Then, the Conclusion of the abstract claimed HIIT showed "significant improvement in cognitive. Please clarify the specific cognitive domains impacted. The spelling of Substantia Nigra is inconsistent (e.g., 'Substantial' in paragraph 1). The claim that HIIT 'reduces the risk of PD' is a strong primary prevention claim. Add appropriate citations supporting this claim. Unless the cited studies are large-scale longitudinal epidemiological trials, it is more accurate to say HIIT 'may mitigate symptom progression' or 'improve neuroplastic markers' in existing cases. Vagueness in the Research Gap: The rationale for the review would be strengthened by briefly mentioning whether any previous meta-analyses exist and why they are insufficient (e.g., they didn't isolate early-stage PD or lacked sufficient HIIT-specific trials at the time). Methodology : The author needs to clarify the scope of the review. The title and abstract suggest a head-to-head comparison between HIIT and aerobic training, but the methodology allows for 'usual care' or 'no treatment' controls. If 'usual care' studies are included, the conclusion that HIIT is superior to aerobic training may be confounded by studies that only compared HIIT to a sedentary group. The methodology states that the second reviewer only screened and validated 10% of the studies and data extraction. For a systematic review to meet PRISMA standards, it is standard practice for two reviewers to independently screen 100% of the titles/abstracts and full texts, and to perform the risk of bias assessment independently for all included studies to ensure reliability. The primary and secondary outcomes are too broadly defined. The author should list the specific validated tools or biomarkers they were looking for (e.g., VO2peak, UPDRS Part III, BDNF levels). This prevents 'selective outcome reporting' bias. The author mentions the feasibility of a meta-analysis but lacks a statistical plan. Please specify which software (e.g., RevMan, R, STATA) and which statistical models (e.g., Random-effects vs. Fixed-effects) would be employed. Additionally, how will heterogeneity be assessed (e.g., I 2 statistic)? The description of the narrative synthesis is vague. The author should specify if they followed a specific framework, such as the SWiM (Synthesis Without Meta-analysis) guidelines, to ensure the process was transparent and not just a subjective summary. There is a chronological discrepancy regarding the search period. The abstract cites July 2025, while the methodology cites April 2025. Please ensure the dates reflect completed work and are consistent throughout the manuscript. The term 'early-stage PD' requires a strict clinical definition in the eligibility criteria (e.g., Hoehn and Yahr stage ≤ 2 or < 5 years since diagnosis). Without this, the population becomes too heterogeneous for a meaningful synthesis. Result: The author notes 'significant heterogeneity' but does not quantify it (e.g., I 2 value) or explain how it impacted the synthesis. If heterogeneity was high, a narrative synthesis must be extremely rigorous in exploring why the results varied (e.g., differences in HIIT intensity or PD duration). Regarding Domain 2 of the RoB2, the author should clarify if 'High Risk' was assigned simply because participants were not blinded (which is standard in exercise trials) or because the outcome assessors were also not blinded. If the assessors were blinded, the risk may actually be 'Low' or have 'Some Concerns' rather than 'High'. The Results section is currently a 'meta-report' (reporting on the studies themselves) rather than a 'data report.' To support the Conclusion that HIIT is superior, the Results must include the specific mean differences, p-values, or effect sizes for the primary outcomes. Currently, the reader has no data to verify the author's later claims. There is a contradiction between the Methodology and the Results. The author previously stated that the second reviewer screened only 10% of citations, yet the Results claim 100% agreement on study selection. Please clarify if the second reviewer eventually screened 100% of the 238 studies, or if the 100% agreement only refers to the 10% sample. Discussion: The author claims HIIT improves cognitive function, citing Fiorelli et al. However, that study investigated an acute bout of exercise. It is a leap in logic to conclude that HIIT provides long-term cognitive neuroprotection based on a single-session study, especially when other results in this review suggest cognitive measures remained largely unchanged. Please temper this claim. The author emphasizes the 'High Risk' of bias due to lack of blinding. However, in exercise science, it is physically impossible to blind participants to the intervention. High-quality trials instead focus on blinding the outcome assessor . The discussion should distinguish between these two; if the assessors were blinded, the 'High Risk' label might be an over-penalization that unfairly devalues the evidence. The terminology for the comparator group is inconsistent throughout the Discussion (MICT vs. MICE vs. Aerobic). For clarity, please standardize to one term (ideally MICT) to distinguish it from the HIIT protocol. While the discussion of BDNF is relevant, the author should be cautious about implying 'neurorestorative' effects in humans. BDNF is a marker of plasticity, but its direct link to 'slowing disease progression' in PD patients is still a hypothesis, not a proven fact. Frame this as a 'potential mechanism' rather than a confirmed outcome. The author concludes that there are "no serious AEs" and the intervention is safe, but then notes that HIIT had the highest number of reported AEs (8/65) and a case of a blood pressure drop. This should be highlighted as a clinical consideration for 'tailoring' exercise, rather than just stating it is 'safe and tolerable'. The Discussion mentions that 'intensity fidelity' was an issue in unsupervised settings (only 77% HRmax achieved). The author should provide a specific clinical recommendation: Does this mean HIIT in PD should always be supervised? This would add significant value to future research. Are the rationale for, and objectives of, the Systematic Review clearly stated? Partly Are sufficient details of the methods and analysis provided to allow replication by others? No Is the statistical analysis and its interpretation appropriate? Partly Are the conclusions drawn adequately supported by the results presented in the review? Yes If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Yes References 1. Nath P, Roy B, Panigrahi S, Islam K, et al.: Recent Trends in Physical Therapy Interventions and Neuromodulation Techniques to Improve Neurorehabilitation. CNS & Neurological Disorders - Drug Targets . 2025; 24 (7): 521-545 Publisher Full Text Competing Interests: No competing interests were disclosed. Reviewer Expertise: exercise, cognition, vestibular rehabilitation, neurology, physiotherapy, neuro-rehabilitation I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Roy B. Reviewer Report For: The efficacy of High Intensity Interval Training (HIIT) versus aerobic exercise in the early stage of Parkinson’s Disease: A Systematic Review [version 1; peer review: 1 approved with reservations, 1 not approved] . F1000Research 2025, 14 :1273 ( https://doi.org/10.5256/f1000research.187448.r438769 ) The direct URL for this report is: https://f1000research.com/articles/14-1273/v1#referee-response-438769 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Paz Rodriguez F. Reviewer Report For: The efficacy of High Intensity Interval Training (HIIT) versus aerobic exercise in the early stage of Parkinson’s Disease: A Systematic Review [version 1; peer review: 1 approved with reservations, 1 not approved] . F1000Research 2025, 14 :1273 ( https://doi.org/10.5256/f1000research.187448.r438760 ) The direct URL for this report is: https://f1000research.com/articles/14-1273/v1#referee-response-438760 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 18 Dec 2025 Francisco Paz Rodriguez , National Institute of Neurology and Neurosurgery “Manuel Velasco Suárez”, Mexico City, Mexico Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.187448.r438760 Thank you for allowing me to review "The efficacy of High Intensity Interval Training (HIIT) versus aerobic exercise in the early stage of Parkinson’s Disease: A Systematic Review." The introduction is well-developed, but in paragraph 5, "Aerobic training is a ... Continue reading READ ALL Thank you for allowing me to review "The efficacy of High Intensity Interval Training (HIIT) versus aerobic exercise in the early stage of Parkinson’s Disease: A Systematic Review." The introduction is well-developed, but in paragraph 5, "Aerobic training is a physical activity aimed at increasing HR," the meaning of HR is not explained. In the methodology section, when describing the type of study, it is not specified what RCTs mean. The typography in Figure 1 is unclear. The reason why 206 studies were excluded is not described. I believe that in Table 4, in the study duration section, the time could be standardized in weeks. In Table 5, in the description of the study by Fernandes et al. (2021), it is not specified what HIIE and MICE mean; is it HIIT? Also, in the same table, the names of the tests should be capitalized: Trail Making Test, Timed Up and Go, and 6-minute Walking Tests. High-intensity exercise is a powerful "medicine" for Parkinson's disease patients, and studies suggest it can positively influence disease progression. However, moderate aerobic exercise remains an option for comprehensive disease management. Any exercise program must be personalized and supervised by healthcare professionals, such as physical or occupational therapists, to ensure safety and maximize benefits. Are the rationale for, and objectives of, the Systematic Review clearly stated? Yes Are sufficient details of the methods and analysis provided to allow replication by others? Yes Is the statistical analysis and its interpretation appropriate? Yes Are the conclusions drawn adequately supported by the results presented in the review? Yes If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Yes References 1. Sena I, Costa A, Santos I, Araújo D, et al.: 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 . 2023; 18 (11). Publisher Full Text 2. Kóra S, Wersényi G, Prukner P, Drotár I, et al.: Effectiveness of High-Intensity Therapy in Rehabilitation of Parkinson’s Disease Patients. Applied Sciences . 2025; 15 (11). Publisher Full Text Competing Interests: No competing interests were disclosed. Reviewer Expertise: Applied research in social neuroscience. Development and implementation of workshops for patients and families with neurodegenerative diseases (Cognitive behavioral therapy, Virtual Reality, Dance). I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Paz Rodriguez F. Reviewer Report For: The efficacy of High Intensity Interval Training (HIIT) versus aerobic exercise in the early stage of Parkinson’s Disease: A Systematic Review [version 1; peer review: 1 approved with reservations, 1 not approved] . F1000Research 2025, 14 :1273 ( https://doi.org/10.5256/f1000research.187448.r438760 ) The direct URL for this report is: https://f1000research.com/articles/14-1273/v1#referee-response-438760 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 18 Nov 2025 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 Version 1 18 Nov 25 read read Francisco Paz Rodriguez , National Institute of Neurology and Neurosurgery “Manuel Velasco Suárez”, Mexico City, Mexico Barnana Roy , Garden City University, Bengaluru, India Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Roy B. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 27 Dec 2025 | for Version 1 Barnana Roy , Garden City University, Bengaluru, Karnataka, India 0 Views copyright © 2025 Roy B. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Not Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer’s Comments on Manuscript Dear Authors, I have carefully reviewed the manuscript titled “The efficacy of High Intensity Interval Training (HIIT) versus aerobic exercise in the early stage of Parkinson’s Disease: A Systematic Review”. The manuscript addresses an important and clinically relevant question by comparing the efficacy of high-intensity interval training (HIIT) and aerobic exercise in individuals with early-stage Parkinson’s disease. However, several aspects of the manuscript require clarification and strengthening to improve scientific rigor, transparency, and alignment with systematic review standards. We believe that addressing these issues will substantially enhance the clarity and scientific rigor of this manuscript. Below, I outline the comments for each section (Introduction, Methodology, Results). Introduction: In the section discussing pharmacological management and neurorehabilitation (starting with "Pharmacological management, engagement in physical activity..."), the authors may wish to incorporate a reference to "Recent Trends in Physical Therapy Interventions and Neuromodulation Techniques to Improve Neurorehabilitation." (P Nath et.al., 2025). Integrating this article would provide a smoother transition from standard medical management to the specific discussion on exercise-induced neuroplasticity by highlighting emerging trends in physical therapy and neuromodulation. Contradiction in Cognitive Findings: One sentence states, "The authors found improved... executive function... while most cognitive measures remained unchanged." Then, the Conclusion of the abstract claimed HIIT showed "significant improvement in cognitive. Please clarify the specific cognitive domains impacted. The spelling of Substantia Nigra is inconsistent (e.g., 'Substantial' in paragraph 1). The claim that HIIT 'reduces the risk of PD' is a strong primary prevention claim. Add appropriate citations supporting this claim. Unless the cited studies are large-scale longitudinal epidemiological trials, it is more accurate to say HIIT 'may mitigate symptom progression' or 'improve neuroplastic markers' in existing cases. Vagueness in the Research Gap: The rationale for the review would be strengthened by briefly mentioning whether any previous meta-analyses exist and why they are insufficient (e.g., they didn't isolate early-stage PD or lacked sufficient HIIT-specific trials at the time). Methodology : The author needs to clarify the scope of the review. The title and abstract suggest a head-to-head comparison between HIIT and aerobic training, but the methodology allows for 'usual care' or 'no treatment' controls. If 'usual care' studies are included, the conclusion that HIIT is superior to aerobic training may be confounded by studies that only compared HIIT to a sedentary group. The methodology states that the second reviewer only screened and validated 10% of the studies and data extraction. For a systematic review to meet PRISMA standards, it is standard practice for two reviewers to independently screen 100% of the titles/abstracts and full texts, and to perform the risk of bias assessment independently for all included studies to ensure reliability. The primary and secondary outcomes are too broadly defined. The author should list the specific validated tools or biomarkers they were looking for (e.g., VO2peak, UPDRS Part III, BDNF levels). This prevents 'selective outcome reporting' bias. The author mentions the feasibility of a meta-analysis but lacks a statistical plan. Please specify which software (e.g., RevMan, R, STATA) and which statistical models (e.g., Random-effects vs. Fixed-effects) would be employed. Additionally, how will heterogeneity be assessed (e.g., I 2 statistic)? The description of the narrative synthesis is vague. The author should specify if they followed a specific framework, such as the SWiM (Synthesis Without Meta-analysis) guidelines, to ensure the process was transparent and not just a subjective summary. There is a chronological discrepancy regarding the search period. The abstract cites July 2025, while the methodology cites April 2025. Please ensure the dates reflect completed work and are consistent throughout the manuscript. The term 'early-stage PD' requires a strict clinical definition in the eligibility criteria (e.g., Hoehn and Yahr stage ≤ 2 or < 5 years since diagnosis). Without this, the population becomes too heterogeneous for a meaningful synthesis. Result: The author notes 'significant heterogeneity' but does not quantify it (e.g., I 2 value) or explain how it impacted the synthesis. If heterogeneity was high, a narrative synthesis must be extremely rigorous in exploring why the results varied (e.g., differences in HIIT intensity or PD duration). Regarding Domain 2 of the RoB2, the author should clarify if 'High Risk' was assigned simply because participants were not blinded (which is standard in exercise trials) or because the outcome assessors were also not blinded. If the assessors were blinded, the risk may actually be 'Low' or have 'Some Concerns' rather than 'High'. The Results section is currently a 'meta-report' (reporting on the studies themselves) rather than a 'data report.' To support the Conclusion that HIIT is superior, the Results must include the specific mean differences, p-values, or effect sizes for the primary outcomes. Currently, the reader has no data to verify the author's later claims. There is a contradiction between the Methodology and the Results. The author previously stated that the second reviewer screened only 10% of citations, yet the Results claim 100% agreement on study selection. Please clarify if the second reviewer eventually screened 100% of the 238 studies, or if the 100% agreement only refers to the 10% sample. Discussion: The author claims HIIT improves cognitive function, citing Fiorelli et al. However, that study investigated an acute bout of exercise. It is a leap in logic to conclude that HIIT provides long-term cognitive neuroprotection based on a single-session study, especially when other results in this review suggest cognitive measures remained largely unchanged. Please temper this claim. The author emphasizes the 'High Risk' of bias due to lack of blinding. However, in exercise science, it is physically impossible to blind participants to the intervention. High-quality trials instead focus on blinding the outcome assessor . The discussion should distinguish between these two; if the assessors were blinded, the 'High Risk' label might be an over-penalization that unfairly devalues the evidence. The terminology for the comparator group is inconsistent throughout the Discussion (MICT vs. MICE vs. Aerobic). For clarity, please standardize to one term (ideally MICT) to distinguish it from the HIIT protocol. While the discussion of BDNF is relevant, the author should be cautious about implying 'neurorestorative' effects in humans. BDNF is a marker of plasticity, but its direct link to 'slowing disease progression' in PD patients is still a hypothesis, not a proven fact. Frame this as a 'potential mechanism' rather than a confirmed outcome. The author concludes that there are "no serious AEs" and the intervention is safe, but then notes that HIIT had the highest number of reported AEs (8/65) and a case of a blood pressure drop. This should be highlighted as a clinical consideration for 'tailoring' exercise, rather than just stating it is 'safe and tolerable'. The Discussion mentions that 'intensity fidelity' was an issue in unsupervised settings (only 77% HRmax achieved). The author should provide a specific clinical recommendation: Does this mean HIIT in PD should always be supervised? This would add significant value to future research. Are the rationale for, and objectives of, the Systematic Review clearly stated? Partly Are sufficient details of the methods and analysis provided to allow replication by others? No Is the statistical analysis and its interpretation appropriate? Partly Are the conclusions drawn adequately supported by the results presented in the review? Yes If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Yes References 1. Nath P, Roy B, Panigrahi S, Islam K, et al.: Recent Trends in Physical Therapy Interventions and Neuromodulation Techniques to Improve Neurorehabilitation. CNS & Neurological Disorders - Drug Targets . 2025; 24 (7): 521-545 Publisher Full Text Competing Interests No competing interests were disclosed. Reviewer Expertise exercise, cognition, vestibular rehabilitation, neurology, physiotherapy, neuro-rehabilitation I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. reply Respond to this report Responses (0) Roy B. Peer Review Report For: The efficacy of High Intensity Interval Training (HIIT) versus aerobic exercise in the early stage of Parkinson’s Disease: A Systematic Review [version 1; peer review: 1 approved with reservations, 1 not approved] . F1000Research 2025, 14 :1273 ( https://doi.org/10.5256/f1000research.187448.r438769) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-1273/v1#referee-response-438769 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Paz Rodriguez F. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 18 Dec 2025 | for Version 1 Francisco Paz Rodriguez , National Institute of Neurology and Neurosurgery “Manuel Velasco Suárez”, Mexico City, Mexico 0 Views copyright © 2025 Paz Rodriguez F. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Thank you for allowing me to review "The efficacy of High Intensity Interval Training (HIIT) versus aerobic exercise in the early stage of Parkinson’s Disease: A Systematic Review." The introduction is well-developed, but in paragraph 5, "Aerobic training is a physical activity aimed at increasing HR," the meaning of HR is not explained. In the methodology section, when describing the type of study, it is not specified what RCTs mean. The typography in Figure 1 is unclear. The reason why 206 studies were excluded is not described. I believe that in Table 4, in the study duration section, the time could be standardized in weeks. In Table 5, in the description of the study by Fernandes et al. (2021), it is not specified what HIIE and MICE mean; is it HIIT? Also, in the same table, the names of the tests should be capitalized: Trail Making Test, Timed Up and Go, and 6-minute Walking Tests. High-intensity exercise is a powerful "medicine" for Parkinson's disease patients, and studies suggest it can positively influence disease progression. However, moderate aerobic exercise remains an option for comprehensive disease management. Any exercise program must be personalized and supervised by healthcare professionals, such as physical or occupational therapists, to ensure safety and maximize benefits. Are the rationale for, and objectives of, the Systematic Review clearly stated? Yes Are sufficient details of the methods and analysis provided to allow replication by others? Yes Is the statistical analysis and its interpretation appropriate? Yes Are the conclusions drawn adequately supported by the results presented in the review? Yes If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Yes References 1. Sena I, Costa A, Santos I, Araújo D, et al.: 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 . 2023; 18 (11). Publisher Full Text 2. Kóra S, Wersényi G, Prukner P, Drotár I, et al.: Effectiveness of High-Intensity Therapy in Rehabilitation of Parkinson’s Disease Patients. Applied Sciences . 2025; 15 (11). Publisher Full Text Competing Interests No competing interests were disclosed. Reviewer Expertise Applied research in social neuroscience. Development and implementation of workshops for patients and families with neurodegenerative diseases (Cognitive behavioral therapy, Virtual Reality, Dance). I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Paz Rodriguez F. Peer Review Report For: The efficacy of High Intensity Interval Training (HIIT) versus aerobic exercise in the early stage of Parkinson’s Disease: A Systematic Review [version 1; peer review: 1 approved with reservations, 1 not approved] . F1000Research 2025, 14 :1273 ( https://doi.org/10.5256/f1000research.187448.r438760) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-1273/v1#referee-response-438760 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. 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