Exploring circular RNAs as biomarkers for Parkinson's disease and their expression changes after aerobic exercise rehabilitation.

Circular RNAs (circRNAs) are circularized single-stranded ribonucleic acids that interacts with DNA, RNA, and proteins to play critical roles in cell biology. CircRNAs regulate microRNA content, gene expression, and may code for specific peptides. Indeed, circRNAs are differentially expressed in neurodegenerative disorders like Parkinson's disease (PD), playing a potential role in the mechanisms of brain pathology. The RNA molecules with aberrant expression in the brain can cross the blood-brain barrier and reach the bloodstream, which enable their use as non-invasive PD disease biomarker. Promising targets with valuable discriminatory ability in combined circRNA signatures include MAPK9_circ_0001566, SLAIN1_circ_0000497, SLAIN2_circ_0126525, PSEN1_circ_0003848, circ_0004381, and circ_0017204. On the other hand, regular exercises are effective therapy for mitigating PD symptoms, promoting neuroprotective effects with epigenetic modulation. Aerobic exercises slow symptom progression in PD by improving motor control, ameliorating higher functions, and enhancing brain activity and neuropathology. These improvements are accompanied by changes circRNA expression, including hsa_circ_0001535 (circFAM13B) and hsa_circ_0000437 (circCORO1C). The sensitivity of current methods for detecting circulating circRNAs is considered a limitation. While amplification kits already exist for low-abundant microRNAs, similar kits are needed for circRNAs. Alternatively, the use of digital PCR can help overcome this constraint. The current review examines the potential use of circRNAs as non-invasive biomarkers of PD and to assess the effects of rehabilitation. Although circRNAs hold promise as targets for PD diagnosis and therapeutics, further validation is needed before their clinical implementation.

Compassionate mind training for people with Parkinson's disease: A pilot study and predictors of response.

INTRODUCTION: People with Parkinson's disease (PD) often present with disabling neuropsychiatric symptoms. Compassionate mind training (CMT) is a psychological approach effective in reducing stress and promoting psychological well-being. Heart rate variability (HRV), a measure reflecting sympathovagal balance, has been associated with psychological well-being and a compassionate attitude. AIM: To assess the feasibility and effectiveness of CMT in enhancing the quality of life and psychological well-being in PD patients. Additionally, we evaluated HRV as a physiomarker for assessing the CMT outcomes. METHODS: Twenty-four PD patients participated in the study. A 6-week online CMT intervention was delivered on a weekly basis. At baseline and post-intervention patients completed questionnaires assessing depression, anxiety and quality of life. In a subsample of 11 patients, HRV was measured at baseline and post-intervention in three conditions: at rest, during stress and after 3 min of deep breathing. RESULTS: The attendance rate was 94.3%. Quality of life and perceived stigma improved post-intervention as compared with baseline (p = 0.02 and p = 0.03 for PD Questionnaire-39 total score and Stigma subscore, respectively). After CMT, patients presented better physiological regulation to stress, as measured by higher HRV as compared with baseline (p = 0.005). Notably, patients who were more resilient to stress at baseline (less decrease in HRV during stress) experienced a more substantial reduction in anxiety and depression following CMT. CONCLUSIONS: CMT is feasible and can improve quality of life and stigma in PD patients. HRV emerges as a promising physiomarker for predicting and measuring the outcomes of psychological interventions in PD.

Effectiveness of vestibular rehabilitation on postural balance in Parkinson's disease: a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Postural balance impairment can affect the quality of life of patients with Parkinson's disease. Previous studies have described connections of the vestibular system with postural functions, suggesting a potential participation of the basal ganglia in receiving vestibular stimuli. This systematic review aims to summarize the evidence on the effectiveness of vestibular rehabilitation on postural balance in patients with Parkinson's disease. METHODS: A systematic review was conducted using the electronic databases: PubMed, Embase, Scopus and PEDro. The study selection was independently conducted by two reviewers, and disagreements were evaluated by a third reviewer. The included studies had no restrictions on publication dates or languages and the last update occurred in July 2023. RESULTS: From the 485 studies found in the searches, only 3 studies were deemed eligible for the systematic review involving a total of 130 participants. The Berg Balance Scale was described as the tool for evaluation of postural balance in all studies. The meta-analysis showed statistically significant results in favor of vestibular rehabilitation (MD = 5.35; 95% CI = 2.39, 8.31; P < 0.001), regardless of the stage of Parkinson's disease. Although the effect size was suggested as a useful functional gain, the analysis was done with caution, as it only included 3 randomized controlled trials. The risk of bias using the RoB-2 was considered as being of "some concern" in all studies. Furthermore, the quality of the evidence based on the Grading of Recommendations Assessment Development and Evaluation system, produced by pooling the included studies was considered very low. CONCLUSION: Compared to other interventions, vestibular rehabilitation has potential to assist the postural balance of patients with Parkinson's disease. However, the very low quality of the evidence demonstrates uncertainty about the impact of this clinical practice. More robust studies are needed to confirm the benefits of this therapy in patients with Parkinson's disease. This study was prospectively registered in PROSPERO: CRD42020210185.

Bicycling for Rehabilitation of Persons With Parkinson Disease: A Scoping Review.

BACKGROUND AND PURPOSE: Exercise is beneficial for persons with Parkinson disease (PwPD). The overarching purpose of this scoping review was to provide guidance to clinicians and scientists regarding current evidence for bicycling exercise for PwPD. A scoping review was conducted to examine the heterogeneous literature on stationary bicycling for PwPD to reduce motor symptoms and body function structure impairments, improve activities and motor performance, and reduce disease severity. METHODS: The Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines were followed. PubMed, CINAHL, and PEDro were searched from inception to January 23, 2023. Articles reporting original data on relevant outcome measures were included. Search results were screened and articles were extracted. Data were analyzed quantitatively with percentages of significant and clinically meaningful findings and qualitatively to extract themes. RESULTS: Bicycling was categorized using bicycle types (assisted, nonassisted) and training modes (speed, aerobic, force). A high percentage of the 34 studies showed statistical significance for reducing motor symptoms (83%), body function structure impairments (78%), disease severity (82%), and improving activities (gait 72%, balance 60%). Clinically meaningful findings were achieved in 71% of the studies for reduction in disease severity and in 50% for improving gait. DISCUSSION AND CONCLUSIONS: The literature on bicycling for PwPD has evolved from speed to aerobic studies. The terminology describing types of bicycling was simplified. Of all the outcomes reported, reduction of disease severity achieved the highest frequency of clinical meaningful improvements. Bicycling was comparable with other forms of aerobic training for walking speed and endurance. Opportunities for translation to practice and research are presented.

Improving Executive Function and Dual-Task Cost in Parkinson Disease: A Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Dual-task walking is challenging for people with Parkinson disease (PD). Gait performance worsens while executing dual tasks, possibly due to a decline in executive function (EF). This study aimed to investigate the effects of dual-task training on EF and dual-task cost (DTC) in people with PD and to explore whether training-induced changes in EF were associated with changes in DTC. METHODS: This study was a randomized controlled trial. A total of 28 people with PD participated. Participants were randomly assigned to the experimental group (dual-task training) and the control group (treadmill training). Both groups received a total of 16 training sessions during the 8 weeks. Assessments were conducted at baseline and postintervention. Primary outcomes included EF and dual-task cost. RESULTS: Significant time-by-group interactions were found in executive function and DTC. The experimental group showed significant improvement in frontal assessment battery (FAB), trail-making test (TMT) part A, Stroop color and word test (SCWT), and DTC on speed in cognitive dual-task walking. There was a moderate to high correlation between the change values of the FAB, TMT part A, SCWT, and the change values of DTC in cognitive dual-task walking. DISCUSSION AND CONCLUSIONS: Compared to treadmill training, dual-task training resulted in greater improvements in EF and DTC. Training-induced changes in EF were linked to changes in DTC when walking while performing a cognitive task but not when walking while performing a motor task. VIDEO ABSTRACT: For more insights from the authors Supplemental Digital Content available at http://links.lww.com/JNPT/A485.

Generalization of In-Place Balance Perturbation Training in People With Parkinson Disease.

BACKGROUND AND PURPOSE: Reactive balance training improves reactive postural control in people with Parkinson disease (PwPD). However, the extent to which reactive balance training generalizes to a novel, unpracticed reactive balance task is unknown. This study aimed to determine whether reactive training stepping through support surface translations can be generalized to an unpracticed, instrumented tether-release task. METHODS: Twenty-five PwPD (70.52 years ± 7.15; Hoehn and Yahr range 1-3) completed a multiple baseline, open-label, uncontrolled pre-post intervention study. Stepping was trained through a 2-week (6-session) intervention with repeated support surface translations. Performance on an untrained tether-release task (generalization task) was measured at 2 baseline assessments (B1 and B2, 2 weeks apart), immediately after the intervention (P1), and 2 months after training (P2). The tether-release task outcomes were the anterior-posterior margin of stability (MOS), step length, and step latency during backward and forward steps. RESULTS: After support surface translation practice, tether-release stepping performance improved in MOS, step length, and step latency for both backward and forward steps compared to baseline ( P < 0.05). Improvements in MOS and step length during backward and forward steps in the tether-release task, respectively, were related to stepping changes in the practiced task. However, the improvements in the generalization task were not retained for 2 months. DISCUSSION AND CONCLUSIONS: These findings support short-term generalization from trained balance tasks to novel, untrained tasks. These findings contribute to our understanding of the effects and generalization of reactive step training in PwPD. VIDEO ABSTRACT AVAILABLE: for more insights from the authors (see the Video, Supplemental Digital Content available at http://links.lww.com/JNPT/A465 ).

Physical exercise for people with Parkinson's disease: a systematic review and network meta-analysis.

BACKGROUND: Physical exercise is effective in managing Parkinson's disease (PD), but the relative benefit of different exercise types remains unclear. OBJECTIVES: To compare the effects of different types of physical exercise in adults with PD on the severity of motor signs, quality of life (QoL), and the occurrence of adverse events, and to generate a clinically meaningful treatment ranking using network meta-analyses (NMAs). SEARCH METHODS: An experienced information specialist performed a systematic search for relevant articles in CENTRAL, MEDLINE, Embase, and five other databases to 17 May 2021. We also searched trial registries, conference proceedings, and reference lists of identified studies up to this date. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing one type of physical exercise for adults with PD to another type of exercise, a control group, or both. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data. A third author was involved in case of disagreements. We categorized the interventions and analyzed their effects on the severity of motor signs, QoL, freezing of gait, and functional mobility and balance up to six weeks after the intervention using NMAs. Two review authors independently assessed the risk of bias using the risk of bias 2 (RoB 2) tool and rated the confidence in the evidence using the CINeMA approach for results on the severity of motor signs and QoL. We consulted a third review author to resolve any disagreements. Due to heterogeneous reporting of adverse events, we summarized safety data narratively and rated our confidence in the evidence using the GRADE approach. MAIN RESULTS: We included 154 RCTs with a total of 7837 participants with mostly mild to moderate disease and no major cognitive impairment. The number of participants per study was small (mean 51, range from 10 to 474). The NMAs on the severity of motor signs and QoL included data from 60 (2721 participants), and 48 (3029 participants) trials, respectively. Eighty-five studies (5192 participants) provided safety data. Here, we present the main results. We observed evidence of beneficial effects for most types of physical exercise included in our review compared to a passive control group. The effects on the severity of motor signs and QoL are expressed as scores on the motor scale of the Unified Parkinson's Disease Rating Scale (UPDRS-M) and the Parkinson's Disease Questionnaire 39 (PDQ-39), respectively. For both scales, higher scores denote higher symptom burden. Therefore, negative estimates reflect improvement (minimum clinically important difference: -2.5 for UPDRS-M and -4.72 for PDQ-39). Severity of motor signs The evidence from the NMA (60 studies; 2721 participants) suggests that dance and gait/balance/functional training probably have a moderate beneficial effect on the severity of motor signs (dance: mean difference (MD) -10.18, 95% confidence interval (CI) -14.87 to -5.36; gait/balance/functional training: MD -7.50, 95% CI -11.39 to -3.48; moderate confidence), and multi-domain training probably has a small beneficial effect on the severity of motor signs (MD -5.90, 95% CI -9.11 to -2.68; moderate confidence). The evidence also suggests that endurance, aqua-based, strength/resistance, and mind-body training might have a small beneficial effect on the severity of motor signs (endurance training: MD -5.76, 95% CI -9.78 to -1.74; aqua-based training: MD -5.09, 95% CI -10.45 to 0.40; strength/resistance training: MD -4.96, 95% CI -9.51 to -0.40; mind-body training: MD -3.62, 95% CI -7.24 to 0.00; low confidence). The evidence is very uncertain about the effects of "Lee Silverman Voice training BIG" (LSVT BIG) and flexibility training on the severity of motor signs (LSVT BIG: MD -6.70, 95% CI -16.48 to 3.08; flexibility training: MD 4.20, 95% CI -1.61 to 9.92; very low confidence). Quality of life The evidence from the NMA (48 studies; 3029 participants) suggests that aqua-based training probably has a large beneficial effect on QoL (MD -15.15, 95% CI -23.43 to -6.87; moderate confidence). The evidence also suggests that mind-body, gait/balance/functional, and multi-domain training and dance might have a small beneficial effect on QoL (mind-body training: MD -7.22, 95% CI -13.57 to -0.70; gait/balance/functional training: MD -6.17, 95% CI -10.75 to -1.59; multi-domain training: MD -5.29, 95% CI -9.51 to -1.06; dance: MD -3.88, 95% CI -10.92 to 3.00; low confidence). The evidence is very uncertain about the effects of gaming, strength/resistance, endurance, and flexibility training on QoL (gaming: MD -8.99, 95% CI -23.43 to 5.46; strength/resistance training: MD -6.70, 95% CI -12.86 to -0.35; endurance training: MD -6.52, 95% CI -13.74 to 0.88; flexibility training: MD 1.94, 95% CI -10.40 to 14.27; very low confidence). Adverse events Only 85 studies (5192 participants) provided some kind of safety data, mostly only for the intervention groups. No adverse events (AEs) occurred in 40 studies and no serious AEs occurred in four studies. AEs occurred in 28 studies. The most frequently reported events were falls (18 studies) and pain (10 studies). The evidence is very uncertain about the effect of physical exercise on the risk of adverse events (very low confidence). Across outcomes, we observed little evidence of differences between exercise types. AUTHORS' CONCLUSIONS: We found evidence of beneficial effects on the severity of motor signs and QoL for most types of physical exercise for people with PD included in this review, but little evidence of differences between these interventions. Thus, our review highlights the importance of physical exercise regarding our primary outcomes severity of motor signs and QoL, while the exact exercise type might be secondary. Notably, this conclusion is consistent with the possibility that specific motor symptoms may be treated most effectively by PD-specific programs. Although the evidence is very uncertain about the effect of exercise on the risk of adverse events, the interventions included in our review were described as relatively safe. Larger, well-conducted studies are needed to increase confidence in the evidence. Additional studies recruiting people with advanced disease severity and cognitive impairment might help extend the generalizability of our findings to a broader range of people with PD.

Rehabilitation activities with tablet (REACT) in Parkinson's disease.

INTRODUCTION: There is evidence to demonstrate that plasticity is "use-dependent" and that intensive practice may be necessary to modify neural organization. PURPOSE: The main aim of this work is to investigate the REACT usability, an innovative app, to assist People with Parkinson Disease (PwPD) at home. METHODS: A pilot study has been conducted enrolling 20 consecutive PwPD. Before home rehabilitation activities started, each patient received training on the REACT app and how to use the device and the services in daily practice. Motor and cognitive evaluations were administered to assign personalized exercises, tailored to patients' needs and potential. PwPD carried out REACT home program for 1 month, four times a week. The app included motor exercise and tutorial of activities of daily living (ADL) and functional cognitive stimulation. REACT-app usability was evaluated with the System Usability Scale (SUS). RESULTS: The results from SUS questionnaire were, on average, above the threshold of "good usability" (SUS score > 68), as reported in the literature. The 47% of PwPD that used the app rated the usability of the solution as "excellent." Almost all SUS items reached the reference benchmark (except items 4, 5, and 7). No adverse events occurred. CONCLUSIONS: REACT can be considered a useful and safe tool to support the continuity of care and treatment at home, in PwPD. Larger-scale trials are needed to validate the good acceptance and efficacy of home rehabilitation through technology applications.

LSVT® BIG versus progressive structured mobility training through synchronous telerehabilitation in Parkinson's disease: A randomized controlled trial.

BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative illness associated with motor symptoms. AIM: The aim of study was to compare the effects of synchronous telerehabilitation-based Lee Silverman Voice Treatment® BIG (LSVT® BIG) protocol and progressive structured mobility training in patients with Parkinson's disease (PD). METHODS: Thirty-two patients diagnosed with PD (aged 40-72 years, Hoehn-Yahr stage 1-3) were randomly allocated into LSVT® BIG (Group 1) and Progressive Structured Mobility Training (Group 2) groups. Exercises were performed in both groups for 60 min a day, 4 days a week, for 4 weeks under the supervision of a physiotherapist with synchronous online videoconference method. Dynamic balance was assessed with Mini-Balance Evaluation Systems Test (Mini-BESTest) as a primary outcome measure. The secondary outcome measurements were Timed Up and Go Test (TUG), spatiotemporal parameters of gait from Kinovea® software, and postural stability from the Biodex Balance System. Other outcome measures were Activity-Specific Balance Confidence Scale-Short Form (ABC-SF), Parkinson's Activity Scale (PAS), and Parkinson's Disease Quality of Life Questionnaire (PDQ-39). RESULTS: This study showed significant group-by-time interactions on Mini-BEST (p = 0.042), ABC-SF (p = 0.029), and PAS (p = 0.022) in favor of group 1. Also, TUG (p < 0.01), spatiotemporal parameters of gait (p < 0.01), and PDQ-39 (p < 0.01) were improved in both groups. CONCLUSION: Both synchronous telerehabilitation-based exercise protocols enhanced balance and gait, as well as activity level and quality of life in patients with PD. LSVT® BIG may be preferred to improve dynamic balance, balance confidence, and activity status in the early stages of PD. These results should be confirmed in future studies with more robust methodology. TRIAL REGISTRATION: NCT04694872.

Effectiveness of Balance Exercise and Brisk Walking on Alleviating Nonmotor and Motor Symptoms in People With Mild-to-Moderate Parkinson Disease: A Randomized Clinical Trial With 6-Month Follow-up.

OBJECTIVE: To investigate the effects of balance exercise and brisk walking on nonmotor and motor symptoms, balance and gait functions, walking capacity, and balance confidence in Parkinson disease (PD) at posttraining and 6-month follow-up. DESIGN: Two-arm, assessor-blinded randomized controlled trial SETTING: University research laboratory and the community PARTICIPANTS: Ninety-nine eligible individuals with mild-to-moderate PD INTERVENTIONS: Participants were randomized to balance and brisk walking group (B&B, n=49) or active control group (n=50). B&B received ten 90-minute sessions of balance exercises and brisk walking supervised by physical therapists for 6 months (week 1-6: weekly, week 7-26: monthly), whereas control practiced whole-body flexibility and upper limb strength exercise at same dosage (180 min/wk). Both groups performed unsupervised home exercises 2-3 times/wk during intervention and continued at follow-up. MAIN OUTCOME MEASURES: Primary outcomes were Movement Disorder Society Unified Parkinson Disease Rating Scale nonmotor (MDS-UPDRS-I) and motor (MDS-UPRDS-III) scores. Secondary outcomes were mini-Balance Evaluation Systems Test (mini-BEST) score, comfortable gait speed (CGS), 6-minute walk test (6MWT), dual-task timed-Up-and-Go (DTUG) time, and Activities-Specific Balance Confidence Scale score. RESULTS: Eighty-three individuals completed the 6-month intervention with no severe adverse effects. The mean between-group (95% CI) difference for the MDS-UPDRS nonmotor score was 1.50 (0.19-2.81) at 6 months and 1.09 (-0.66 to 2.85) at 12 months. The mean between-group (95% CI) difference for the MDS-UPDRS motor score was 3.75 (0.69-6.80) at 6 months and 4.57 (1.05-8.01) at 12 months. At 6 and 12 months, there were significant between-group improvements of the B&B group in mini-BEST score, CGS, 6MWT, and DTUG time. CONCLUSIONS: This combined balance and brisk walking exercise program alleviates nonmotor and motor symptoms and improves walking capacity, balance, and gait functions posttraining, with positive carryover effects for all except nonmotor outcomes, at 6-month follow-up in mild-to-moderate PD.

The 'PD Warrior' exercise programme improves motor outcomes and quality of life in patients with early Parkinson disease: results of a pilot study.

BACKGROUND: 'PD Warrior' (PDW) is a popular exercise programme for Parkinson disease; however, there are no published studies on the outcomes of the programme. AIMS: To investigate short-term functional and quality of life (QoL) outcomes after the PDW 10-week programme in a pilot study of individuals with early Parkinson Disease (PD). METHODS: Twenty individuals with PD (Hoehn & Yahr 1-3) attending a hospital outpatient clinic were recruited into the PDW 10-week programme, comprising a weekly 1-h supervised class complemented by an individualised daily home exercise programme. Participants had the following assessments at baseline and after completion of the programme: Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) Part III, timed up-and-go (TUG), 10-m walk test (10mWT), 6-min walking test (6MWT), balance tests, fine motor skills, 7-day Parkinson KinetiGraph (PKG) and PDQ-39 QoL scale. RESULTS: Seventeen individuals completed the programme. Significant improvements were observed in MDS-UPDRS motor score (P = 0.019, d = 0.68, MCID 7); 6MWT distance (P < 0.001, d = 1.16); walking time during motor or cognitive dual tasking (P = 0.006, d = 0.77; P = 0.005, d = 0.79, respectively); and the PDQ-39 emotional well-being subdomain (P = 0.009; MCID 4.2); as well as improvements trending to significance in bradykinesia (P = 0.025, d = 0.73), 10mWT walking time (P = 0.023, d = 0.61) and borderline improvement in balance (P = 0.056, d = 0.50). CONCLUSIONS: The outcomes of this study support the efficacy of the PDW programme in individuals with early PD and provide justification for future trials and investigation of its effects.

Vertical locomotion improves horizontal locomotion: effects of climbing on gait and other mobility aspects in Parkinson's disease. A secondary analysis from a randomized controlled trial.

BACKGROUND: In the Climb Up! Head Up! trial, we showed that sport climbing reduces bradykinesia, tremor, and rigidity in mildly to moderately affected participants with Parkinson's disease. This secondary analysis aimed to evaluate the effects of sport climbing on gait and functional mobility in this cohort. METHODS: Climb Up! Head Up! was a 1:1 randomized controlled trial. Forty-eight PD participants (Hoehn and Yahr stage 2-3) either participated in a 12-week, 90-min-per-week sport climbing course (intervention group) or were engaged in regular unsupervised physical activity (control group). Relevant outcome measures for this analysis were extracted from six inertial measurement units placed on the extremities, chest, and lower back, that were worn during supervised gait and functional mobility assessments before and after the intervention. Assessments included normal and fast walking, dual-tasking walking, Timed Up and Go test, Instrumented Stand and Walk test, and Five Times Sit to Stand test. RESULTS: Compared to baseline, climbing improved gait speed during normal walking by 0.09 m/s (p = 0.005) and during fast walking by 0.1 m/s. Climbing also reduced the time spent in the stance phase during fast walking by 0.03 s. Climbing improved the walking speed in the 7-m- Timed Up and Go test by 0.1 m/s (p < 0.001) and the turning speed by 0.39 s (p = 0.052), the speed in the Instrumented Stand and Walk test by 0.1 m/s (p < 0.001), and the speed in the Five Times Sit to Stand test by 2.5 s (p = 0.014). There was no effect of sport climbing on gait speed or gait variables during dual-task walking. CONCLUSIONS: Sport climbing improves gait speed during normal and fast walking, as well as functional mobility in people with Parkinson's disease. Trial registration This study was registered within the U.S. National Library of Medicine (No: NCT04569981, date of registration September 30th, 2020).

Effects of transcranial direct current stimulation alone and in combination with rehabilitation therapies on gait and balance among individuals with Parkinson's disease: a systematic review and meta-analysis.

BACKGROUND: Parkinson's disease (PD) is a neurogenerative disorder implicated in dysfunctions of motor functions, particularly gait and balance. Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation offered as a potential adjuvant therapy for PD. This systematic review and meta-analysis were conducted to identify whether tDCS alone and combined with additional rehabilitation therapies improve gait and balance among individuals with PD. METHODS: We searched PubMed, Embase, Web of Science, and relevant databases for eligible studies from inception to December 2022. Studies with a comparative design investigating the effects of tDCS on motor functions, including gait and balance among individuals with PD, were included. A meta-analysis was performed for each outcome using a random effects model for subgroup analysis and pooling of overall effect sizes. RESULTS: A total of 23 studies were included in the meta-analysis. The pooled results revealed that tDCS has moderate overall effects on gait, measured by gait speed (standardized mean deviation [SMD] = 0.238; 95% confidence interval [CI] - 0.026 to 0.502); stride length (SMD = 0.318; 95% CI - 0.015 to 0.652); cadence (SMD = - 0.632; 95% CI - 0.932 to - 0.333); freezing of gait questionnaire scores (SMD = - 0.360; 95% CI - 0.692 to - 0.027); step length (SMD = 0.459; 95% CI - 0.031 to 0.949); walking time (SMD = - 0.253; 95% CI - 0.758 to 0.252); stride time (SMD = - 0.785; 95% CI: - 1.680 to 0.111); double support time (SMD = 1.139; 95% CI - 0.244 to 0.523); and balance, measured by timed up and go (TUG) test (SMD = - 0.294; 95% CI - 0.516 to - 0.073), Berg balance scale (BBS) scores (SMD = 0.406; 95% CI - 0.059 to 0.87), and dynamic gait index (SMD = 0.275; 95% CI - 0.349 to 0.898). For the subgroup analysis, gait and balance demonstrated moderate effect sizes. However, only cadence, stride time, and TUG indicated a significant difference between real and sham tDCS (P = 0.027, P = 0.002, and P = 0.023, respectively), whereas cadence and BBS (P < 0.01 and P = 0.045, respectively) significantly differed after real tDCS plus other therapies rather than after sham tDCS plus other therapies. CONCLUSIONS: Our results indicated that tDCS is significantly associated with gait and balance improvements among individuals with PD. The findings of this study provide more proof supporting the effectiveness of tDCS, encouraging tDCS to be utilized alone or in combination with other therapies in clinical practice for PD rehabilitation.

Brain modulation after exergaming training in advanced forms of Parkinson's disease: a randomized controlled study.

BACKGROUND: Physical activity combined with virtual reality and exergaming has emerged as a new technique to improve engagement and provide clinical benefit for gait and balance disorders in people with Parkinson's disease (PD). OBJECTIVE: To investigate the effects of a training protocol using a home-based exergaming system on brain volume and resting-state functional connectivity (rs-FC) in persons with PD. METHODS: A single blind randomized controlled trial was conducted in people with PD with gait and/or balance disorders. The experimental (active) group performed 18 training sessions at home by playing a custom-designed exergame with full body movements, standing in front of a RGB-D Kinect® motion sensor, while the control group played using the computer keyboard. Both groups received the same training program. Clinical scales, gait recordings, and brain MRI were performed before and after training. We assessed the effects of both training on both the grey matter volumes (GVM) and rs-FC, within and between groups. RESULTS: Twenty-three patients were enrolled and randomly assigned to either the active (n = 11) or control (n = 12) training groups. Comparing pre- to post-training, the active group showed significant improvements in gait and balance disorders, with decreased rs-FC between the sensorimotor, attentional and basal ganglia networks, but with an increase between the cerebellar and basal ganglia networks. In contrast, the control group showed no significant changes, and rs-FC significantly decreased in the mesolimbic and visuospatial cerebellar and basal ganglia networks. Post-training, the rs-FC was greater in the active relative to the control group between the basal ganglia, motor cortical and cerebellar areas, and bilaterally between the insula and the inferior temporal lobe. Conversely, rs FC was lower in the active relative to the control group between the pedunculopontine nucleus and cerebellar areas, between the temporal inferior lobes and the right thalamus, between the left putamen and dorsolateral prefrontal cortex, and within the default mode network. CONCLUSIONS: Full-body movement training using a customized exergame induced brain rs-FC changes within the sensorimotor, attentional and cerebellar networks in people with PD. Further research is needed to comprehensively understand the neurophysiological effects of such training approaches. Trial registration ClinicalTrials.gov NCT03560089.

A gamified virtual environment intervention for gait rehabilitation in Parkinson's Disease: co-creation and feasibility study.

BACKGROUND: Treadmill gait training has been shown to improve gait performance in People with Parkinson's Disease (PwPD), and in combination with Virtual Reality, it can be an effective tool for gait rehabilitation. The addition of gamification elements can create a more stimulating and adherent intervention. However, implementation of new technologies in healthcare can be challenging. This study aimed to develop and evaluate the feasibility of a treadmill rehabilitation program in a Gamified Virtual Reality Environment (GVRE) for PwPD. METHODS: The GVRE was developed following a user-centered design approach, involving both PwPD and physiotherapists in the development and evaluation of the intervention. The intervention consisted of a walking simulation in three different environments (countryside, city, and park), which had a progressive increase in difficulty. To test its feasibility, three sessions were carried out with four PwPD and four physiotherapists. To assess the usability, the System Usability Scale (SUS), Assistive Technology Usability Questionnaire for people with Neurological diseases (NATU Quest) and Simulator Sickness Questionnaire (SSQ) were used. To assess the intervention's acceptability, feedback and in-game performance was collected from participants. RESULTS: Results showed the feasibility of the intervention, with a SUS score of 74.82 ± 12.62, and a NATU Quest score of 4.49 ± 0.62, and positive acceptability feedback. Participants showed clear preferences for naturalistic environments, and gamification elements were seen as positive. Difficulty settings worked as intended, but lowered enjoyment of the experience in some cases. CONCLUSIONS: This intervention was successfully shown as a feasible option for the training of gait under Dual Task conditions for PwPD. It offers a safe and replicable environment in which complex situations can be trained. However, further iterations of the intervention need to be improved in order to guarantee accurate tracking and a more realistic training progression. TRIAL REGISTRATION NUMBER: NCT05243394-01/20/2022.

The inertial-based gait normalcy index of dual task cost during turning quantifies gait automaticity improvement in early-stage Parkinson's rehabilitation.

BACKGROUND: The loss of gait automaticity is a key cause of motor deficits in Parkinson's disease (PD) patients, even at the early stage of the disease. Action observation training (AOT) shows promise in enhancing gait automaticity. However, effective assessment methods are lacking. We aimed to propose a novel gait normalcy index based on dual task cost (NIDTC) and evaluate its validity and responsiveness for early-stage PD rehabilitation. METHODS: Thirty early-stage PD patients were recruited and randomly assigned to the AOT or active control (CON) group. The proposed NIDTC during straight walking and turning tasks and clinical scale scores were measured before and after 12 weeks of rehabilitation. The correlations between the NIDTCs and clinical scores were analyzed with Pearson correlation coefficient analysis to evaluate the construct validity. The rehabilitative changes were assessed using repeated-measures ANOVA, while the responsiveness of NIDTC was further compared by t tests. RESULTS: The turning-based NIDTC was significantly correlated with multiple clinical scales. Significant group-time interactions were observed for the turning-based NIDTC (F = 4.669, p = 0.042), BBS (F = 6.050, p = 0.022) and PDQ-39 (F = 7.772, p = 0.011) tests. The turning-based NIDTC reflected different rehabilitation effects between the AOT and CON groups, with the largest effect size (p = 0.020, Cohen's d = 0.933). CONCLUSION: The turning-based NIDTC exhibited the highest responsiveness for identifying gait automaticity improvement by providing a comprehensive representation of motor ability during dual tasks. It has great potential as a valid measure for early-stage PD diagnosis and rehabilitation assessment. Trial registration Chinese Clinical Trial Registry: ChiCTR2300067657.

Clinical and neurophysiological effects of bilateral repetitive transcranial magnetic stimulation and EEG-guided neurofeedback in Parkinson's disease: a randomized, four-arm controlled trial.

BACKGROUND: Repetitive Transcranial Magnetic Stimulation (rTMS) and EEG-guided neurofeedback techniques can reduce motor symptoms in Parkinson's disease (PD). However, the effects of their combination are unknown. Our objective was to determine the immediate and short-term effects on motor and non-motor symptoms, and neurophysiological measures, of rTMS and EEG-guided neurofeedback, alone or combined, compared to no intervention, in people with PD. METHODS: A randomized, single-blinded controlled trial with 4 arms was conducted. Group A received eight bilateral, high-frequency (10 Hz) rTMS sessions over the Primary Motor Cortices; Group B received eight 30-minute EEG-guided neurofeedback sessions focused on reducing average bilateral alpha and beta bands; Group C received a combination of A and B; Group D did not receive any therapy. The primary outcome measure was the UPDRS-III at post-intervention and two weeks later. Secondary outcomes were functional mobility, limits of stability, depression, health-related quality-of-life and cortical silent periods. Treatment effects were obtained by longitudinal analysis of covariance mixed-effects models. RESULTS: Forty people with PD participated (27 males, age = 63 ± 8.26 years, baseline UPDRS-III = 15.63 ± 6.99 points, H&Y = 1-3). Group C showed the largest effect on motor symptoms, health-related quality-of-life and cortical silent periods, followed by Group A and Group B. Negligible differences between Groups A-C and Group D for functional mobility or limits of stability were found. CONCLUSIONS: The combination of rTMS and EEG-guided neurofeedback diminished overall motor symptoms and increased quality-of-life, but this was not reflected by changes in functional mobility, postural stability or depression levels. TRIAL REGISTRATION: NCT04017481.

Wearable biofeedback device to assess gait features and improve gait pattern in people with parkinson's disease: a case series.

INTRODUCTION: People with Parkinson's Disease (PD) show abnormal gait patterns compromising their independence and quality of life. Among all gait alterations due to PD, reduced step length, increased cadence, and decreased ground-reaction force during the loading response and push-off phases are the most common. Wearable biofeedback technologies offer the possibility to provide correlated single or multi-modal stimuli associated with specific gait events or gait performance, hence promoting subjects' awareness of their gait disturbances. Moreover, the portability and applicability in clinical and home settings for gait rehabilitation increase the efficiency in the management of PD. The Wearable Vibrotactile Bidirectional Interface (BI) is a biofeedback device designed to extract gait features in real-time and deliver a customized vibrotactile stimulus at the waist of PD subjects synchronously with specific gait phases. The aims of this study were to measure the effect of the BI on gait parameters usually compromised by the typical bradykinetic gait and to assess its usability and safety in clinical practice. METHODS: In this case series, seven subjects (age: 70.4 ± 8.1 years; H&Y: 2.7 ± 0.3) used the BI and performed a test on a 10-meter walkway (10mWT) and a two-minute walk test (2MWT) as pre-training (Pre-trn) and post-training (Post-trn) assessments. Gait tests were executed in random order with (Bf) and without (No-Bf) the activation of the biofeedback stimulus. All subjects performed three training sessions of 40 min to familiarize themselves with the BI during walking activities. A descriptive analysis of gait parameters (i.e., gait speed, step length, cadence, walking distance, double-support phase) was carried out. The 2-sided Wilcoxon sign-test was used to assess differences between Bf and No-Bf assessments (p < 0.05). RESULTS: After training subjects improved gait speed (Pre-trn_No-Bf: 0.72(0.59,0.72) m/sec; Post-trn_Bf: 0.95(0.69,0.98) m/sec; p = 0.043) and step length (Pre-trn_No-Bf: 0.87(0.81,0.96) meters; Post-trn_Bf: 1.05(0.96,1.14) meters; p = 0.023) using the biofeedback during the 10mWT. Similarly, subjects' walking distance improved (Pre-trn_No-Bf: 97.5 (80.3,110.8) meters; Post-trn_Bf: 118.5(99.3,129.3) meters; p = 0.028) and the duration of the double-support phase decreased (Pre-trn_No-Bf: 29.7(26.8,31.7) %; Post-trn_Bf: 27.2(24.6,28.7) %; p = 0.018) during the 2MWT. An immediate effect of the BI was detected in cadence (Pre-trn_No-Bf: 108(103.8,116.7) step/min; Pre-trn_Bf: 101.4(96.3,111.4) step/min; p = 0.028) at Pre-trn, and in walking distance at Post-trn (Post-trn_No-Bf: 112.5(97.5,124.5) meters; Post-trn_Bf: 118.5(99.3,129.3) meters; p = 0.043). SUS scores were 77.5 in five subjects and 80.3 in two subjects. In terms of safety, all subjects completed the protocol without any adverse events. CONCLUSION: The BI seems to be usable and safe for PD users. Temporal gait parameters have been measured during clinical walking tests providing detailed outcomes. A short period of training with the BI suggests improvements in the gait patterns of people with PD. This research serves as preliminary support for future integration of the BI as an instrument for clinical assessment and rehabilitation in people with PD, both in hospital and remote environments. TRIAL REGISTRATION: The study protocol was registered (DGDMF.VI/P/I.5.i.m.2/2019/1297) and approved by the General Directorate of Medical Devices and Pharmaceutical Service of the Italian Ministry of Health and by the ethics committee of the Lombardy region (Milan, Italy).

Cerebellar tDCS combined with augmented reality treadmill for freezing of gait in Parkinson's disease: a randomized controlled trial.

BACKGROUND: Parkinson's disease (PD) is often accompanied by gait disorders and freezing of gait (FoG), disabling symptoms that are resistant to conventional dopamine treatments. Given the cerebellum's connectivity with the motor cortex and basal ganglia, and its implication in PD, combining transcranial direct current stimulation targeting the cerebellum (ctDCS) with physical exercise might improve gait and balance. OBJECTIVE: This study aimed to evaluate the effectiveness of a novel rehabilitation approach that combines noninvasive cerebellar stimulation with motor-cognitive training via an augmented reality treadmill (C-Mill VR+) in individuals with PD and FoG. METHODS: Seventeen individuals with PD exhibiting FoG were enrolled in a randomized controlled trial. The participants were randomly assigned to a group receiving motor-cognitive training on the C-Mill VR+ with either ctDCS or sham ctDCS. Assessments were conducted pre-intervention (T0), post-intervention (T1) after 10 sessions, and at 4-week follow-up (T2), using various clinical scales. Additionally, C-Mill assessments of postural stability and gait were conducted at T0 and T1. RESULTS: Although no significant time*group interactions were observed for any of the clinical variables measured, some were found in the C-Mill measures. Specifically, right lower limb sway in static conditions, both with eyes open (OAD) and eyes closed (OCD), significantly improved at T1 in the ctDCS group compared with the sham group. CONCLUSIONS: C-Mill outcomes indicate that the combined treatment may enhance motor control. Participants who received ctDCS along with augmented reality motor-cognitive training showed better postural stability.

The impact of PD Check-In on self-management skills for maintenance of speech after intensive treatment.

BACKGROUND: Maintenance of speech outcomes following speech-language therapy (SLT) in Parkinson's disease (PD) is an unmet expectation of people with PD (PWPD) and poorly defined in SLT practice. PD Check-In, a model for supported self-managed maintenance of speech following Lee Silverman Voice Treatment (LSVT) LOUD was investigated. AIMS: To investigate the impact of the semi-structured component of PD Check-In on the adoption of self-management concepts and behaviours and the identification of facilitators, barriers and strategies for speech maintenance by PWPD over 24 months post-treatment. METHODS AND PROCEDURE: Following LSVT LOUD, 16 PWPD participated in individual PD Check-In semi-structured discussions with a SLT at 6 and 12 weeks, and 6, 12 and 24 months post treatment. A two-stage qualitative content analysis was applied: directed content analysis using categories from the theoretical framework of PD Check-In followed by inductive content analysis to identify subcategories. OUTCOMES AND RESULTS: Statements from PWPD indicated adoption of seven concepts of self-management across participants and across time. Six concepts from the theoretical framework of PD Check-In (partnerships, self-reflection, maintenance barriers and facilitators, revision of LSVT LOUD skill, goal setting and maintenance strategies), and one new category, participation, emerged from the analysis. Self-reflection, maintenance facilitators and barriers and participation were most prevalent in discussions. PWPD identified facilitators, barriers and strategies for maintenance across time points. CONCLUSIONS AND IMPLICATIONS: Statements from PWPD indicated a positive impact of SLT-supported self-management of speech using self-tailored strategies for sustainable maintenance according to their individual circumstances and needs. WHAT THIS PAPER ADDS: What is already known on this subject People with Parkinson's disease (PWPD) have expressed their need for speech-language therapy (SLT) services that are accessible for the duration of the condition and responsive to their expectation of maintaining speech following treatment. Outcomes for maintenance of the treatment effect following Lee Silverman Voice Treatment (LSVT) LOUD are variable. What this paper adds to existing knowledge This study presents the outcomes of five PD Check-In interventions delivered in semi-structured discussions between PWPD and a SLT over 24 months following LSVT LOUD for the development of self-management skills and behaviours. PWPD adopted self-management positively using self-tailored strategies for sustainable maintenance according to their individual circumstances and needs. What are the potential or actual clinical implications of this work? PWPD responded positively to the individual development of self-management skills and behaviours over time. Individuality and flexible responsivity are features of PD Check-In which resonate with PWPD and speak to SLT supported self-managed maintenance of speech as a long-term model for PD.