Possible improvement of social adjustment after subthalamic deep brain stimulation in people with Parkinson's disease? A systematic review and meta-analysis.

Interactions with others need social adjustment (i.e., the constant accommodation to changing social situations). Mixed evidence indicates positive as well as negative changes in social adjustment after subthalamic nucleus deep brain stimulation (STN-DBS) in people with Parkinson's Disease (PwPD). To date, however, no meta-analysis of these changes exists. Thus, the study aim was to review evidence of the effects of STN-DBS on social adjustment in PwPD. For this purpose, a systematic literature search in MEDLINE was conducted. The meta-analysis was performed using a random effects model and standardized mean differences (SMDs) with 95% confidence intervals (CIs). The MINORS tool was used to assess the methodological quality of the studies. The initial literature search identified 13,124 articles, of which 1,550 full texts were assessed for eligibility. Eight studies were finally included; for seven articles sufficient data for a meta-analysis was available. Most studies found mild impairment in social adjustment impairment pre-surgery. The meta-analysis revealed no significant changes but a statistical trend towards improvement in social adjustment up to six months (SMD = 0.25; 95%CI=-0.03,0.53; P = 0.08) and over 12 months (SMD = 0.26; 95%CI=-0.03,0.55; P = 0.07) post-surgery. Methodological quality was moderate in 87.5% of the studies and good in 12.5%. While mild impairment in social adjustment pre-surgery was reported in most studies, the data indicate that STN-DBS might yield beneficial effects toward this outcome. However, not enough data yet exists to draw firm conclusions. As a crucial skill for everyday functioning, social adjustment should be more often defined as an outcome in STN-DBS trials in PwPD and should be considered in clinical routines.

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.

Can Physical Exercise Be Considered as a Promising Enhancer of Global Cognition in People with Parkinson's Disease? Results of a Systematic Review and Meta-Analysis.

Background: Physical exercise interventions are known to improve quality of life, motor and non-motor symptoms in people with Parkinson's disease (PD). However, systematic reviews and meta-analyses on cognitive outcomes are rare. Objective: To perform a systematic review and meta-analysis of physical exercise intervention effects compared with passive and active control groups (CGs) on global cognition in people with PD. Methods: A literature search was performed for randomized controlled trials (RCTs) on physical exercise interventions in PD using nine databases. We included RCTs reporting global cognition outcomes. A meta-analysis was performed using random-effects models and standardized mean differences (SMDs) with 95% confidence intervals (CIs). Bias was assessed with the revised Cochrane Risk of Bias tool and the certainty of evidence was rated using the GRADE approach. Results: Seventeen studies (ten with passive, seven with active CGs) were included in the systematic review. Exercise interventions varied considerably between studies. The meta-analysis included nine studies with 236 people with PD (seven with passive, two with active CGs). The SMD was 0.33 (95% CI 0.00; 0.65) demonstrating a small effect (p = 0.05) in favor of physical exercise. Compared with passive CGs, physical exercise had a small non-significant effect (SMD = 0.22, 95% CI -0.14;0.58, p = 0.24). Compared with active CGs, physical exercise had a medium significant effect (SMD = 0.72, 95% CI 0.12;1.33, p = 0.02). Conclusions: Physical exercise may increase global cognition in people with PD, but the evidence is very uncertain. Further large-scale RCTs are needed to confirm this finding and to identify the most effective type of physical exercise for improving cognition.

Physical Exercise as a Potential Treatment for Fatigue in Parkinson's Disease? A Systematic Review and Meta-Analysis of Pharmacological and Non-Pharmacological Interventions.

BACKGROUND: Fatigue is one of the most common and debilitating non-motor symptoms among patients with Parkinson's disease (PD) and significantly impacts quality of life. Therefore, effective treatment options are needed. OBJECTIVE: To provide an update on randomized controlled trials (RCTs) including pharmacological and non-pharmacological (but non-surgical) treatments that examine the effects of fatigue on PD patients. METHODS: We searched the MEDLINE, EMBASE, PsycINFO, CENTRAL, and CINAHL databases for (cross-over) RCTs on pharmacological and non-pharmacological interventions for treating fatigue in PD patients until May 2021. Meta-analyses for random-effects models were calculated when two or more studies on the same treatment option were available using standardized mean differences (SMDs) with 95% confidence intervals (CIs). RESULTS: Fourteen pharmacological and 16 non-pharmacological intervention RCTs were identified. For pharmacological approaches, a meta-analysis could only be performed for modafinil compared to placebo (n = 2) revealing a non-significant effect on fatigue (SMD = - 0.21, 95% CI - 0.74-0.31, p = 0.43). Regarding non-pharmacological approaches, physical exercise (n = 8) following different training approaches versus passive or placebo control groups showed a small significant effect (SMD = - 0.37, 95% CI - 0.69- - 0.05, p = 0.02) which could not be demonstrated for acupuncture vs. sham-acupuncture (SMD = 0.16, 95% CI - 0.19-0.50, p = 0.37). CONCLUSION: Physical exercise may be a promising strategy to treat fatigue in PD patients. Further research is required to examine the efficacy of this treatment strategy and further interventions. Future studies should differentiate treatment effects on physical and mental fatigue as the different underlying mechanisms of these symptoms may lead to different treatment responses. More effort is required to develop, evaluate, and implement holistic fatigue management strategies for PD patients.

Assessing safety and treatment efficacy of running on intervertebral discs (ASTEROID) in adults with chronic low back pain: protocol for a randomised controlled trial.

Poor intervertebral disc (IVD) health is associated with low back pain (LBP). This 12-week parallel randomised controlled trial will evaluate the efficacy of a progressive interval running programme on IVD health and other clinical outcomes in adults with chronic LBP. Participants will be randomised to either a digitally delivered progressive interval running programme or waitlist control. Participants randomised to the running programme will receive three individually tailored 30 min community-based sessions per week over 12 weeks. The waitlist control will undergo no formal intervention. All participants will be assessed at baseline, 6 and 12 weeks. Primary outcomes are IVD health (lumbar IVD T2 via MRI), average LBP intensity over the prior week (100-point visual analogue scale) and disability (Oswestry Disability Index). Secondary outcomes include a range of clinical measures. All outcomes will be analysed using linear mixed models. This study has received ethical approval from the Deakin University Human Research Ethics Committee (ID: 2022-162). All participants will provide informed written consent before participation. Regardless of the results, the findings of this study will be disseminated, and anonymised data will be shared via an online repository. This will be the first study to evaluate whether a progressive interval running programme can improve IVD health in adults with chronic LBP. Identifying conservative options to improve IVD health in this susceptible population group has the potential to markedly reduce the burden of disease. This study was registered via the Australian New Zealand Clinical Trials Registry on 29 September 2022 (ACTRN12622001276741).

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 156 RCTs with a total of 7939 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 71 (3196 participants), and 55 (3283 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 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 (71 studies; 3196 participants) suggests that dance has a moderate beneficial effect on the severity of motor signs (mean difference (MD) -10.32, 95% confidence interval (CI) -15.54 to -4.96; high confidence), and aqua-based, gait/balance/functional, and multi-domain training might have a moderate beneficial effect on the severity of motor signs (aqua-based: MD -7.77, 95% CI -13.27 to -2.28; gait/balance/functional: MD -7.37, 95% CI -11.39 to -3.35; multi-domain: MD -6.97, 95% CI -10.32 to -3.62; low confidence). The evidence also suggests that mind-body training and endurance training might have a small beneficial effect on the severity of motor signs (mind-body: MD -6.57, 95% CI -10.18 to -2.81; endurance: MD -6.43, 95% CI -10.72 to -2.28; low confidence). Flexibility training might have a trivial or no effect on the severity of motor signs (MD 2.01, 95% CI -4.82 to 8.98; low confidence). The evidence is very uncertain about the effects of strength/resistance training and "Lee Silverman Voice training BIG" (LSVT BIG) on the severity of motor signs (strength/resistance: MD -6.97, 95% CI -11.93 to -2.01; LSVT BIG: MD -5.49, 95% CI -14.74 to 3.62; very low confidence). Quality of life The evidence from the NMA (55 studies; 3283 participants) suggests that aqua-based training probably has a large beneficial effect on QoL (MD -14.98, 95% CI -23.26 to -6.52; moderate confidence). The evidence also suggests that endurance training might have a moderate beneficial effect, and that gait/balance/functional and multi-domain training might have a small beneficial effect on QoL (endurance: MD -9.16, 95% CI -15.68 to -2.82; gait/balance/functional: MD -5.64, 95% CI -10.04 to -1.23; multi-domain: MD -5.29, 95% CI -9.34 to -1.06; low confidence). The evidence is very uncertain about the effects of mind-body training, gaming, strength/resistance training, dance, LSVT BIG, and flexibility training on QoL (mind-body: MD -8.81, 95% CI -14.62 to -3.00; gaming: MD -7.05, 95% CI -18.50 to 4.41; strength/resistance: MD -6.34, 95% CI -12.33 to -0.35; dance: MD -4.05, 95% CI -11.28 to 3.00; LSVT BIG: MD 2.29, 95% CI -16.03 to 20.44; flexibility: MD 1.23, 95% CI -11.45 to 13.92; 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.

Effects of Resistance Training on Motor- and Non-Motor Symptoms in Patients with Parkinson's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Previous reviews indicated positive effects of resistance training (RT) on motor outcomes in Parkinson's disease (PD). However, inconsistencies between the included studies exist, and non-motor outcomes have only scarcely been considered in a review on RT in PD. OBJECTIVE: To analyze the RT effects on motor- and non-motor outcomes in PD patients compared to passive and physically active control groups (i.e., other structured physical interventions). METHODS: We searched CENTRAL, MEDLINE, EMBASE, and CINAHL for randomized controlled trials of RT in PD. After identifying 18 studies, a meta-analysis was conducted for the outcomes muscle strength, motor impairment, freezing of gait (FoG), mobility and balance, quality of life (QoL), depression, cognition, and adverse events. Meta-analyses with random models were calculated using mean differences (MD) or standardized mean differences (SMD) with 95% confidence intervals (CI). RESULTS: When comparing RT with passive control groups, the meta-analyses showed significant large effects on muscle strength (SMD = -0.84, 95% CI -1.29--0.39, p = 0.0003), motor impairment (SMD = -0.81, 95% CI -1.34--0.27, p = 0.003), mobility and balance (MD = -1.81, 95% CI -3.13--0.49, p = 0.007), and small significant effects on QoL (SMD = -0.48, 95% CI -0.86--0.10, p = 0.01). RT compared with physically active control groups reached no significant results for any outcome. CONCLUSIONS: RT improves muscle strength, motor impairment, mobility and balance, QoL, and depression in PD patients. However, it is not superior to other physically active interventions. Therefore, exercise is important for PD patients but according to this analysis, its type is of secondary interest.