The prevalence of Parkinson disease (PD) is growing fast, amplifying the quest for disease-modifying therapies in early disease phases where pathology is still limited. Lifestyle interventions offer a promising avenue for preventing progression from prodromal to manifest PD. We illustrate this primarily for 1 specific lifestyle intervention, namely aerobic exercise because the case for the other main lifestyle factor (dietary interventions) to modify the course of prodromal PD is currently less persuasive. Various observations have hinted at the disease-modifying potential of exercise. First, studies in rodents with experimental parkinsonism showed that exercise elicits adaptive neuroplasticity in basal ganglia circuitries. Second, exercise is associated with a reduced risk of developing PD, suggesting a disease-modifying potential. Third, 2 large trials in persons with manifest PD indicate that exercise can help to stabilize motor parkinsonism, although this could also reflect a symptomatic effect. In addition, exercise seems to be a feasible intervention, given its minimal risk of side effects. Theoretical risks include an increase in fall incidents and cardiovascular complications, but these concerns seem to be acceptably low. Innovative approaches using gamification elements indicate that adequate long-term compliance with regular exercise programs can be achieved, although more work remains necessary to demonstrate enduring adherence for multiple years. Advances in digital technology can be used to deliver the exercise intervention in the participant's own living environment and also to measure the outcomes remotely, which will help to further boost long-term compliance. When delivering exercise to prodromal participants, outcome measures should focus not just on phenoconversion to manifest PD (which may well take many years to occur) but also on measurable intermediate outcomes, such as physical fitness or prodromal nonmotor symptoms. Taken together, there seems to be sufficient evidence to advocate the first judicious attempt of investigating exercise as a disease-modifying treatment in prodromal PD.

中文翻译：

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预防帕金森病的生活方式干预：行动指南。

帕金森病 (PD) 的患病率正在快速增长，在病理学仍然有限的早期疾病阶段扩大了对疾病修饰疗法的探索。生活方式干预为预防从前驱期进展为表现性 PD 提供了一条有希望的途径。我们主要针对 1 种特定的生活方式干预，即有氧运动来说明这一点，因为其他主要生活方式因素（饮食干预）来改变前驱 PD 病程的情况目前不太有说服力。各种观察都暗示了运动改变疾病的潜力。首先，对患有实验性帕金森症的啮齿动物的研究表明，运动会引起基底神经节回路的适应性神经可塑性。其次，运动与降低患 PD 的风险有关，这表明运动具有改善疾病的潜力。第三，2 项针对明显 PD 患者的大型试验表明，运动有助于稳定运动性帕金森症，尽管这也可能反映症状效应。此外，鉴于其副作用风险最小，运动似乎是一种可行的干预措施。理论上的风险包括跌倒事件和心血管并发症的增加，但这些担忧似乎低到可以接受。使用游戏化元素的创新方法表明，可以实现对定期锻炼计划的充分长期遵守，尽管仍然需要做更多的工作来证明多年的持久坚持。数字技术的进步可用于在参与者自己的生活环境中提供锻炼干预，也可用于远程测量结果，这将有助于进一步提高长期合规性。在为前驱参与者提供锻炼时，结果测量不仅应关注表型转化为表现 PD（这可能需要很多年才能发生），还应关注可测量的中间结果，例如身体健康或前驱非运动症状。总而言之，似乎有足够的证据支持第一次明智的尝试，将运动作为前驱 PD 的疾病缓解治疗进行调查。