1)山东体育学院研究生教育学院,济南 250102;2)上海体育大学运动健康学院,上海200438
泰山学者工程(tstp20250540)资助项目。
1)College of Graduate Education, Shandong Sport University, Jinan 250102, China;2)School of Exercise and Health, Shanghai University of Sport, Shanghai 200438, China
This work was supported by a grant from TaiShan Scholars (tstp20250540).
帕金森病(Parkinson’s disease,PD)作为全球第二大神经退行性疾病,其患病率随老龄化进程加速而持续攀升。传统运动疗法可通过抑制α突触核蛋白病理性聚集、增强线粒体自噬及调节神经炎症等机制改善运动与非运动症状,但其疗效在PD患者中呈现显著异质性。究其根源:a. PD的遗传背景、分子病理与临床表现呈现高度异质性;b. 临床表型与疾病分期进一步加剧运动干预的复杂性;c. 运动干预应答的个体差异以及对运动参数配置的动态需求。基于此,本文从PD流行病学负担、运动干预疗效异质性以及疾病发病机制等方面描述PD患者为何需要精准运动干预(Why);基于遗传、表型、分期特征设计分层干预路径,并整合技术赋能工具阐述如何构建精准运动干预策略(How);通过运动类型、强度、频率等维度的个性化适配策略叙述运动干预参数的基本配置(What)。
Parkinson"s disease (PD), the second most common neurodegenerative disorder worldwide, presents significant heterogeneity in clinical manifestations, genetic background, and response to interventions. While conventional exercise therapies demonstrate benefits in alleviating motor and non-motor symptoms through mechanisms such as modulating α-synuclein aggregation, enhancing mitophagy, and reducing neuroinflammation, their efficacy varies considerably among individuals. This variability may stem from endogenous factors such as genetic background, clinical phenotypes, stages of pathological progression, as well as exogenous factors like the type, intensity, and frequency of movement. Thus, this review first discusses the necessity of precise exercise interventions for PD patients, focusing on the epidemiological burden, heterogeneity in disease mechanisms, and differences in intervention response (Why). Next, we systematically explain how to develop precise exercise intervention strategies by stratifying interventions based on genetic background, clinical phenotype, and disease stage, combined with technological aids (How). Genetically, mutations in genes such as GBA1, PRKN, PINK1, and SNCA dictate distinct molecular pathologies—including lysosomal dysfunction, impaired mitophagy, and α-synuclein aggregation—which necessitate tailored exercise regimens. For instance, patients with PRKN/PINK1 mutations may benefit from moderate-intensity endurance training to support mitochondrial biogenesis without exacerbating oxidative stress, whereas carriers of GBA1 mutations might require exercises focusing on enhancing lysosomal function and managing oxidative damage. Clinically, patients are stratified into tremor-dominant (TD) and postural instability/gait difficulty (PIGD) subtypes, which demand divergent exercise priorities: coordinative, rhythm-based activities like dance or Tai Chi for TD-PD to engage cerebellar circuits, versus targeted balance and strength training, potentially aided by virtual reality, for PIGD-PD to mitigate axial symptoms and fall risk. Furthermore, intervention strategies must evolve with disease progression: high-intensity exercise is prioritized in early stages to leverage neuroplasticity and potential disease modification, while mid- and late-stage management focuses on functional maintenance, fall prevention, and compensatory strategies, respectively. Critical to implementing this framework is the adoption of digital biomarkers via wearable technology (e.g., inertial sensors, smartwatches), which enables continuous, objective monitoring of gait, tremor, and physiological responses. This facilitates a closed-loop feedback system, allowing for the remote adjustment of exercise parameters (intensity, frequency, duration) in real-time, thus optimizing efficacy and ensuring safety. Finally, we detail how to configure exercise parameters through personalized adaptation (What), including exercise type, intensity, frequency and dose. Higher volumes of physical activity are associated with reduced PD risk and slower progression, though optimal thresholds remain incompletely defined. Aerobic exercise improves cardiovascular fitness and may aid clearance of pathogenic proteins; resistance training counters sarcopenia and bradykinesia; balance training reduces falls; and mind-body exercises (e.g., Tai Chi) integrate motor and cognitive components. Multimodal regimens are often most beneficial. High-intensity aerobic exercise appears particularly effective in early PD, enhancing neural connectivity and mitigating disease progression in randomized trials. Most evidence supports supervised sessions occurring 3–5 times per week, lasting 30–60 min, adapted to individual tolerance and disease stage. In conclusion, this narrative review outlines a comprehensive precision medicine framework for exercise intervention in PD, moving beyond symptomatic management towards targeting underlying pathophysiology. By stratifying patients based on genetic, phenotypic, and staging characteristics, and by leveraging digital technology for dynamic personalization, exercise therapy can be transformed into a more potent, individualized, and disease-modifying strategy. Future research must validate these biomarker-driven approaches in large-scale trials and establish definitive guidelines for translating precision exercise into clinical practice.
周子贵,颜敏,温潇,王慧,刘国强,田雪文.帕金森病精准运动干预的多维体系:基于遗传分型、运动亚型、临床分期和可穿戴生物标志物的动态调控[J].生物化学与生物物理进展,,():
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