Cochrane Haematology, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Medical Psychology, Neuropsychology and Gender Studies and Center for Neuropsychological Diagnostics and Intervention (CeNDI), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Cochrane Database Syst Rev. 2023 Jan 5;1(1):CD013856. doi: 10.1002/14651858.CD013856.pub2.
Physical exercise is effective in managing Parkinson's disease (PD), but the relative benefit of different exercise types remains unclear.
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).
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.
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.
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.
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.
运动锻炼对帕金森病（PD）的管理是有效的，但不同运动类型的相对益处仍不清楚。
比较成人 PD 患者不同类型的身体锻炼在运动体征严重程度、生活质量（QoL）和不良事件发生方面的效果，并使用网络荟萃分析（NMA）生成具有临床意义的治疗排序。
一位经验丰富的信息专家对 CENTRAL、MEDLINE、Embase 和其他五个数据库进行了系统检索，检索时间截至 2021 年 5 月 17 日。我们还检索了试验注册处、会议论文集和确定研究的参考文献列表，截至该日期。
我们纳入了将成人 PD 患者的一种身体锻炼与另一种锻炼、对照组或两者进行比较的随机对照试验（RCT）。
两位综述作者独立提取数据。第三位作者参与了意见分歧的情况。我们对干预措施进行了分类，并使用 NMAs 分析了它们对运动体征严重程度、QoL、冻结步态和功能移动性和平衡的影响，干预后持续 6 周。两位综述作者使用风险偏倚 2 工具（RoB 2）独立评估了风险偏倚，并使用 CINeMA 方法对运动体征严重程度和 QoL 的结果评估了证据的置信度。我们咨询了第三位综述作者，以解决任何分歧。由于不良事件报告存在异质性，我们对安全性数据进行了叙述性总结，并使用 GRADE 方法对证据的置信度进行了评级。
我们纳入了 156 项 RCT，共纳入了 7939 名参与者，其中大多数患有轻度至中度疾病，且没有严重认知障碍。每项研究的参与者人数较少（平均 51 人，范围为 10 至 474 人）。包括 71 项（3196 名参与者）试验的 NMAs 对运动体征严重程度和 QoL 进行了分析，包括 55 项（3283 名参与者）试验的 NMA。85 项研究（5192 名参与者）提供了安全性数据。在这里，我们呈现主要结果。我们观察到与对照组相比，我们综述中包含的大多数类型的身体锻炼都有有益的效果。对运动体征严重程度和 QoL 的影响分别用统一帕金森病评定量表（UPDRS-M）和帕金森病问卷 39 （PDQ-39）的运动量表来表示。这两个量表的得分越高表示症状负担越重。因此，负估计值反映了改善（最小临床重要差异：UPDRS-M 为-2.5，PDQ-39 为-4.72）。运动体征严重程度从 71 项研究（3196 名参与者）的 NMA（统一帕金森病评定量表）中，舞蹈对运动体征严重程度有中度有益的影响（平均差异（MD）-10.32，95%置信区间（CI）-15.54 至-4.96；高置信度），水基、步态/平衡/功能和多领域训练可能对运动体征严重程度有中度有益的影响（水基：MD-7.77，95%CI-13.27 至-2.28；步态/平衡/功能：MD-7.37，95%CI-11.39 至-3.35；多领域：MD-6.97，95%CI-10.32 至-3.62；低置信度）。证据还表明，身心训练和耐力训练可能对运动体征严重程度有较小的有益影响（身心训练：MD-6.57，95%CI-10.18 至-2.81；耐力训练：MD-6.43，95%CI-10.72 至-2.28；低置信度）。灵活性训练可能对运动体征严重程度没有影响或影响很小（MD2.01，95%CI-4.82 至 8.98；低置信度）。证据非常不确定强度/阻力训练和“Lee Silverman 声音训练 BIG”（LSVT BIG）对运动体征严重程度的影响（强度/阻力训练：MD-6.97，95%CI-11.93 至-2.01；LSVT BIG：MD-5.49，95%CI-14.74 至 3.62；非常低置信度）。生活质量从 55 项研究（3283 名参与者）的 NMA 中，我们发现水上训练可能对 QoL 有较大的有益影响（MD-14.98，95%CI-23.26 至-6.52；中等置信度）。证据还表明，耐力训练可能有中度有益的影响，而步态/平衡/功能和多领域训练可能对 QoL 有较小的有益影响（耐力训练：MD-9.16，95%CI-15.68 至-2.82；步态/平衡/功能：MD-5.64，95%CI-10.04 至-1.23；多领域：MD-5.29，95%CI-9.34 至-1.06；低置信度）。证据非常不确定身心训练、游戏、强度/阻力训练、舞蹈、LSVT BIG 和灵活性训练对 QoL 的影响（身心训练：MD-8.81，95%CI-14.62 至-3.00；游戏：MD-7.05，95%CI-18.50 至 4.41；强度/阻力训练：MD-6.34，95%CI-12.33 至-0.35；舞蹈：MD-4.05，95%CI-11.28 至 3.00；LSVT BIG：MD2.29，95%CI-16.03 至 20.44；灵活性：MD1.23，95%CI-11.45 至 13.92；非常低置信度）。不良事件只有 85 项研究（5192 名参与者）提供了一些安全性数据，主要是干预组的安全性数据。40 项研究没有发生任何不良事件，4 项研究没有发生严重不良事件。28 项研究发生了不良事件。最常报告的事件是跌倒（18 项研究）和疼痛（10 项研究）。证据非常不确定运动锻炼对不良事件风险的影响（非常低置信度）。在所有结局中，我们观察到干预之间的差异很小。
我们发现，对于纳入本综述的大多数类型的身体锻炼，PD 患者的运动体征严重程度和 QoL 都有有益的效果，但我们对这些干预措施之间的差异证据很少。因此，我们的综述强调了身体锻炼对我们主要结局运动体征严重程度和 QoL 的重要性，而具体的运动类型可能是次要的。值得注意的是，这一结论与特定运动症状可能通过 PD 特异性方案得到更有效治疗的观点是一致的。尽管关于锻炼对不良事件风险的影响的证据非常不确定，但纳入的干预措施被描述为相对安全。需要更大规模、精心设计的研究来提高证据的可信度。招募病情严重程度和认知障碍较高的患者的额外研究可能有助于将我们的发现扩展到更广泛的 PD 人群。
