Rotondo Rossella, Proietti Stefania, Perluigi Marzia, Padua Elvira, Stocchi Fabrizio, Fini Massimo, Stocchi Vilberto, Volpe Daniele, De Pandis Maria Francesca
San Raffaele Cassino, Cassino, Italy.
Unit of Clinical and Molecular Epidemiology, IRCCS San Raffaele Roma, Rome, Italy.
Ageing Res Rev. 2023 Dec;92:102089. doi: 10.1016/j.arr.2023.102089. Epub 2023 Oct 14.
Parkinson's disease (PD) is a neurodegenerative disorder, characterized by motor and non-motor symptoms, that still lacks of a disease-modifying treatment. Consistent evidence proved the benefits of physical therapy on motor and non-motor symptoms in PD patients, leading the scientific community to propose physical activity as disease-modifying therapy for PD and suggesting the involvement of neurotrophic factors (NFs) as key mediators of neuroplasticity. However, the lack of standardized exercise training and methodological flaws of clinical trials have limited the evidence demonstrating the exercise-induced changes in serum and plasma neurotrophic factors concentration. A systematic search, covering 20 years of research in this field and including randomized and non-randomized controlled trials (RCTs and non-RCTs), which reported changes in serum and plasma NFs after a specific intervention, were reviewed. Pooled effect sizes (p-ESs) and 95% confidence intervals (95%CIs) were calculated using a random effects model with R software. A total of 18 articles, of which exercise programs of interventions were codified in terms of type, intensity and duration adopting a standardisation methodology, were included in the systematic review. Six papers, describing the effect of different training programs on BDNF and IGF-1 levels, were included and independently analysed in two meta-analyses. Quantitative analysis for BDNF indicated a statistically significant improvement in serum concentration of PD patients (MD: 5.99 ng/mL; 95%IC: 0.15 -11.83; I = 77%) performing physical activity compared with control conditions in RCTs. Preliminary evidence supported the hypothesis that a moderate intensity aerobic exercise (MIAE) would be necessary to induce the changes in NFs. However, sensitivity analysis of meta-analysis and the few studies included in subgroup analysis did not support these results. Alongside, meta-analysis followed by sensitivity analysis revealed a potential change in serum IGF-1 (MD: 33.47 ng/mL; 95%IC: 8.09-58.85) in PD patients performing physical activity with respect controls in RCT studies. Considering the limited evidence to support or refute the increase in NFs levels in PD patients performing physical activity, there is a need to develop a rigorous controlled randomized trial, with standardization for loading intensity of physical activity, greater sample size, and a correct stratification of PD patients to establish a well-defined correlation between physical activity and NFs levels.
帕金森病（PD）是一种神经退行性疾病，以运动和非运动症状为特征，目前仍缺乏疾病修饰治疗方法。一致的证据证明了物理治疗对帕金森病患者运动和非运动症状的益处，促使科学界提出体育活动作为帕金森病的疾病修饰疗法，并表明神经营养因子（NFs）作为神经可塑性的关键介质参与其中。然而，缺乏标准化的运动训练以及临床试验的方法学缺陷限制了证明运动引起血清和血浆神经营养因子浓度变化的证据。我们对该领域20年的研究进行了系统检索，包括随机和非随机对照试验（RCT和非RCT），这些试验报告了特定干预后血清和血浆NFs的变化，并进行了综述。使用R软件的随机效应模型计算合并效应量（p-ESs）和95%置信区间（95%CIs）。共有18篇文章被纳入系统评价，其中干预的运动项目根据类型、强度和持续时间采用标准化方法进行了编码。6篇描述不同训练方案对BDNF和IGF-1水平影响的论文被纳入，并在两项荟萃分析中进行独立分析。对BDNF的定量分析表明，与RCT中的对照条件相比，进行体育活动的帕金森病患者血清浓度有统计学意义的改善（MD：5.99 ng/mL；95%IC：0.15 - 11.83；I = 77%）。初步证据支持这样的假设，即中等强度有氧运动（MIAE）对于诱导NFs的变化是必要的。然而，荟萃分析的敏感性分析以及亚组分析中纳入的少数研究并不支持这些结果。此外，荟萃分析及随后的敏感性分析显示，在RCT研究中，进行体育活动的帕金森病患者与对照组相比，血清IGF-1有潜在变化（MD：33.47 ng/mL；95%IC：8.09 - 58.85）。考虑到支持或反驳进行体育活动的帕金森病患者NFs水平升高的证据有限，有必要开展一项严格控制的随机试验，对体育活动的负荷强度进行标准化，增加样本量，并对帕金森病患者进行正确分层，以建立体育活动与NFs水平之间明确的相关性。
