Mechanisms of motor symptom improvement by long-term Tai Chi training in Parkinson's disease patients.
Li Gen,Huang Pei,Cui Shi-Shuang,Tan Yu-Yan,He Ya-Chao,Shen Xin,Jiang Qin-Ying,Huang Ping,He Gui-Ying,Li Bin-Yin,Li Yu-Xin,Xu Jin,Wang Zheng,Chen Sheng-Di
Translational neurodegeneration
BACKGROUND:Tai Chi has been shown to improve motor symptoms in Parkinson's disease (PD), but its long-term effects and the related mechanisms remain to be elucidated. In this study, we investigated the effects of long-term Tai Chi training on motor symptoms in PD and the underlying mechanisms. METHODS:Ninety-five early-stage PD patients were enrolled and randomly divided into Tai Chi (n = 32), brisk walking (n = 31) and no-exercise (n = 32) groups. At baseline, 6 months and 12 months during one-year intervention, all participants underwent motor symptom evaluation by Berg balance scale (BBS), Unified PD rating-scale (UPDRS), Timed Up and Go test (TUG) and 3D gait analysis, functional magnetic resonance imaging (fMRI), plasma cytokine and metabolomics analysis, and blood Huntingtin interaction protein 2 (HIP2) mRNA level analysis. Longitudinal self-changes were calculated using repeated measures ANOVA. GEE (generalized estimating equations) was used to assess factors associated with the longitudinal data of rating scales. Switch rates were used for fMRI analysis. False discovery rate correction was used for multiple correction. RESULTS:Participants in the Tai Chi group had better performance in BBS, UPDRS, TUG and step width. Besides, Tai Chi was advantageous over brisk walking in improving BBS and step width. The improved BBS was correlated with enhanced visual network function and downregulation of interleukin-1β. The improvements in UPDRS were associated with enhanced default mode network function, decreased L-malic acid and 3-phosphoglyceric acid, and increased adenosine and HIP2 mRNA levels. In addition, arginine biosynthesis, urea cycle, tricarboxylic acid cycle and beta oxidation of very-long-chain fatty acids were also improved by Tai Chi training. CONCLUSIONS:Long-term Tai Chi training improves motor function, especially gait and balance, in PD. The underlying mechanisms may include enhanced brain network function, reduced inflammation, improved amino acid metabolism, energy metabolism and neurotransmitter metabolism, and decreased vulnerability to dopaminergic degeneration. Trial registration This study has been registered at Chinese Clinical Trial Registry (Registration number: ChiCTR2000036036; Registration date: August 22, 2020).
10.1186/s40035-022-00280-7
Tai chi and postural stability in patients with Parkinson's disease.
Li Fuzhong,Harmer Peter,Fitzgerald Kathleen,Eckstrom Elizabeth,Stock Ronald,Galver Johnny,Maddalozzo Gianni,Batya Sara S
The New England journal of medicine
BACKGROUND:Patients with Parkinson's disease have substantially impaired balance, leading to diminished functional ability and an increased risk of falling. Although exercise is routinely encouraged by health care providers, few programs have been proven effective. METHODS:We conducted a randomized, controlled trial to determine whether a tailored tai chi program could improve postural control in patients with idiopathic Parkinson's disease. We randomly assigned 195 patients with stage 1 to 4 disease on the Hoehn and Yahr staging scale (which ranges from 1 to 5, with higher stages indicating more severe disease) to one of three groups: tai chi, resistance training, or stretching. The patients participated in 60-minute exercise sessions twice weekly for 24 weeks. The primary outcomes were changes from baseline in the limits-of-stability test (maximum excursion and directional control; range, 0 to 100%). Secondary outcomes included measures of gait and strength, scores on functional-reach and timed up-and-go tests, motor scores on the Unified Parkinson's Disease Rating Scale, and number of falls. RESULTS:The tai chi group performed consistently better than the resistance-training and stretching groups in maximum excursion (between-group difference in the change from baseline, 5.55 percentage points; 95% confidence interval [CI], 1.12 to 9.97; and 11.98 percentage points; 95% CI, 7.21 to 16.74, respectively) and in directional control (10.45 percentage points; 95% CI, 3.89 to 17.00; and 11.38 percentage points; 95% CI, 5.50 to 17.27, respectively). The tai chi group also performed better than the stretching group in all secondary outcomes and outperformed the resistance-training group in stride length and functional reach. Tai chi lowered the incidence of falls as compared with stretching but not as compared with resistance training. The effects of tai chi training were maintained at 3 months after the intervention. No serious adverse events were observed. CONCLUSIONS:Tai chi training appears to reduce balance impairments in patients with mild-to-moderate Parkinson's disease, with additional benefits of improved functional capacity and reduced falls. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00611481.).
10.1056/NEJMoa1107911
Exercise and gait/movement analyses in treatment and diagnosis of Parkinson's Disease.
Ageing research reviews
Cardinal motor symptoms in Parkinson's disease (PD) include bradykinesia, rest tremor and/or rigidity. This symptomatology can additionally encompass abnormal gait, balance and postural patterns at advanced stages of the disease. Besides pharmacological and surgical therapies, physical exercise represents an important strategy for the management of these advanced impairments. Traditionally, diagnosis and classification of such abnormalities have relied on partially subjective evaluations performed by neurologists during short and temporally scattered hospital appointments. Emerging sports medical methods, including wearable sensor-based movement assessment and computational-statistical analysis, are paving the way for more objective and systematic diagnoses in everyday life conditions. These approaches hold promise to facilitate customizing clinical trials to specific PD groups, as well as personalizing neuromodulation therapies and exercise prescriptions for each individual, remotely and regularly, according to disease progression or specific motor symptoms. We aim to summarize exercise benefits for PD with a specific emphasis on gait and balance deficits, and to provide an overview of recent advances in movement analysis approaches, notably from the sports science community, with value for diagnosis and prognosis. Although such techniques are becoming increasingly available, their standardization and optimization for clinical purposes is critically missing, especially in their translation to complex neurodegenerative disorders such as PD. We highlight the importance of integrating state-of-the-art gait and movement analysis approaches, in combination with other motor, electrophysiological or neural biomarkers, to improve the understanding of the diversity of PD phenotypes, their response to therapies and the dynamics of their disease progression.
10.1016/j.arr.2023.102147
The effects of exercise dose on patients with Parkinson's disease: a systematic review and meta-analysis of randomized controlled trials.
Journal of neurology
OBJECTIVE:The effects of different exercise doses on motor function, balance, mobility, and quality of life (QOL) in patients with Parkinson's disease (PD) were evaluated. METHOD:The exercise intervention dose was evaluated based on the recommendations of the American College of Sports Medicine (ACSM) for developing and maintaining cardiorespiratory health, muscle strength, and physical function for PD patients and classified into high ACSM compliance and low or uncertain ACSM compliance. The impact of ACSM compliance on Unified Parkinson's Disease Rating Scale, Part III (UPDRS-III), Berg Balance Scale (BBS), Timed Up and Go (TUG), and 39-item Parkinson's Disease Questionnaire (PDQ-39) in patients with PD was compared using the standardized mean difference (SMD) along with the corresponding 95% confidence interval (95% CI). RESULTS:A total of 26 articles were included, comprising 32 studies. Twenty-one studies were classified as high ACSM compliance, and 11 studies were classified as low or uncertain ACSM compliance. For the four outcome measures, the SMD ratio of exercise interventions with high ACSM compliance to those with low or uncertain ACSM compliance was as follows: UPDRS-III (- 0.74: - 0.17), TUG (- 0.62: - 0.17), PDQ-39 (- 0.58: - 0.31), and BBS (0.51: 0.52). CONCLUSION:The results suggest that compared with exercise interventions with low or uncertain ACSM compliance, exercise interventions with high ACSM compliance had a more significant improvement effect on motor function, mobility, and QOL in PD patients. However, the effect on balance was not as pronounced, and further research is needed to validate these findings.
10.1007/s00415-023-11887-9
Treadmill exercise ameliorates dopaminergic neuronal loss through suppressing microglial activation in Parkinson's disease mice.
Sung Yun-Hee,Kim Shin-Chul,Hong Hoon-Pyo,Park Chang-Youl,Shin Mal-Soon,Kim Chang-Ju,Seo Jin-Hee,Kim Dae-Young,Kim Dong-Je,Cho Han-Jin
Life sciences
AIMS:Parkinson's disease is a debilitating neurodegenerative disorder characterized by the gradual loss of dopaminergic neurons. We investigated the effects of treadmill exercise on dopaminergic neuronal loss and microglial activation using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/P)-induced Parkinson's disease mice. MAIN METHODS:Parkinson's disease was induced in mice by injection of MPTP/P. The mice in the exercise groups were put on a treadmill to run for 30min/day, five times per week for four weeks. Motor balance and coordination was measured using rota-rod test. Expressions of inducible nitric oxide synthase (iNOS) and phosphorylated extracellular signal-regulated kinase (p-ERK), phosphorylated NH(2)-terminal kinase (p-JNK), phosphorylated p-38 (p-p38), CD200, and CD200 receptor were determined by western blotting. Expressions of tyrosine hydroxylase (TH) and CD11b were evaluated by immunohistochemistry. KEY FINDINGS:Parkinson's disease mice displayed poor motor balance and coordination with loss of nigrostriatal dopaminergic neurons. iNOS expression was enhanced via up-regulation of phosphorylated mitogen-activated protein kinases (p-MAPKs) signaling, such as p-ERK, p-JNK, and p-p-38 in the Parkinson's disease mice. Microglial activation was also observed in the Parkinson's disease mice, showing increased CD11b expression with suppressed CD200 and CD200 receptor expressions. Treadmill exercise prevented the loss of nigrostriatal dopaminergic neurons, and ameliorated the motor balance and coordination dysfunction in the Parkinson's disease mice. Treadmill exercise suppressed iNOS expression via down-regulation of MAPKs and also inhibited microglial activation in the Parkinson's disease mice. SIGNIFICANCE:Treadmill exercise prevented dopaminergic neuronal loss by inhibiting brain inflammation through suppression of microglial activation in the Parkinson's disease mice.
10.1016/j.lfs.2012.10.003
Exercise as medicine in Parkinson's disease.
Journal of neurology, neurosurgery, and psychiatry
Parkinson's disease (PD) is an incurable and progressive neurological disorder leading to deleterious motor and non-motor consequences. Presently, no pharmacological agents can prevent PD evolution or progression, while pharmacological symptomatic treatments have limited effects in certain domains and cause side effects. Identification of interventions that prevent, slow, halt or mitigate the disease is therefore pivotal. Exercise is safe and represents a cornerstone in PD rehabilitation, but exercise may have even more fundamental benefits that could change clinical practice. In PD, the existing knowledge base supports exercise as (1) a protective lifestyle factor preventing the disease (ie, primary prevention), (2) a potential disease-modifying therapy (ie, secondary prevention) and (3) an effective symptomatic treatment (ie, tertiary prevention). Based on current evidence, a paradigm shift is proposed, stating that exercise should be individually prescribed as medicine to persons with PD at an early disease stage, alongside conventional medical treatment.
10.1136/jnnp-2023-332974
Addition of a non-immersive virtual reality component to treadmill training to reduce fall risk in older adults (V-TIME): a randomised controlled trial.
Mirelman Anat,Rochester Lynn,Maidan Inbal,Del Din Silvia,Alcock Lisa,Nieuwhof Freek,Rikkert Marcel Olde,Bloem Bastiaan R,Pelosin Elisa,Avanzino Laura,Abbruzzese Giovanni,Dockx Kim,Bekkers Esther,Giladi Nir,Nieuwboer Alice,Hausdorff Jeffrey M
Lancet (London, England)
BACKGROUND:Age-associated motor and cognitive deficits increase the risk of falls, a major cause of morbidity and mortality. Because of the significant ramifications of falls, many interventions have been proposed, but few have aimed to prevent falls via an integrated approach targeting both motor and cognitive function. We aimed to test the hypothesis that an intervention combining treadmill training with non-immersive virtual reality (VR) to target both cognitive aspects of safe ambulation and mobility would lead to fewer falls than would treadmill training alone. METHODS:We carried out this randomised controlled trial at five clinical centres across five countries (Belgium, Israel, Italy, the Netherlands, and the UK). Adults aged 60-90 years with a high risk of falls based on a history of two or more falls in the 6 months before the study and with varied motor and cognitive deficits were randomly assigned by use of computer-based allocation to receive 6 weeks of either treadmill training plus VR or treadmill training alone. Randomisation was stratified by subgroups of patients (those with a history of idiopathic falls, those with mild cognitive impairment, and those with Parkinson's disease) and sex, with stratification per clinical site. Group allocation was done by a third party not involved in onsite study procedures. Both groups aimed to train three times per week for 6 weeks, with each session lasting about 45 min and structured training progression individualised to the participant's level of performance. The VR system consisted of a motion-capture camera and a computer-generated simulation projected on to a large screen, which was specifically designed to reduce fall risk in older adults by including real-life challenges such as obstacles, multiple pathways, and distracters that required continual adjustment of steps. The primary outcome was the incident rate of falls during the 6 months after the end of training, which was assessed in a modified intention-to-treat population. Safety was assessed in all patients who were assigned a treatment. This study is registered with ClinicalTrials.gov, NCT01732653. FINDINGS:Between Jan 6, 2013, and April 3, 2015, 302 adults were randomly assigned to either the treadmill training plus VR group (n=154) or treadmill training alone group (n=148). Data from 282 (93%) participants were included in the prespecified, modified intention-to-treat analysis. Before training, the incident rate of falls was similar in both groups (10·7 [SD 35·6] falls per 6 months for treadmill training alone vs 11·9 [39·5] falls per 6 months for treadmill training plus VR). In the 6 months after training, the incident rate was significantly lower in the treadmill training plus VR group than it had been before training (6·00 [95% CI 4·36-8·25] falls per 6 months; p<0·0001 vs before training), whereas the incident rate did not decrease significantly in the treadmill training alone group (8·27 [5·55-12·31] falls per 6 months; p=0·49). 6 months after the end of training, the incident rate of falls was also significantly lower in the treadmill training plus VR group than in the treadmill training group (incident rate ratio 0·58, 95% CI 0·36-0·96; p=0·033). No serious training-related adverse events occurred. INTERPRETATION:In a diverse group of older adults at high risk for falls, treadmill training plus VR led to reduced fall rates compared with treadmill training alone. FUNDING:European Commission.
10.1016/S0140-6736(16)31325-3
Treadmill exercise reduces α-synuclein spreading via PPARα.
Cell reports
This study underlines the importance of treadmill exercise in reducing α-synuclein (α-syn) spreading in the A53T brain and protecting nigral dopaminergic neurons. Preformed α-syn fibril (PFF) seeding in the internal capsule of young A53T α-syn mice leads to increased spreading of α-syn to substantia nigra and motor cortex and concomitant loss of nigral dopaminergic neurons. However, regular treadmill exercise decreases α-syn spreading in the brain and protects nigral dopaminergic neurons in PFF-seeded mice. Accordingly, treadmill exercise also mitigates α-synucleinopathy in aged A53T mice. While investigating this mechanism, we have observed that treadmill exercise induces the activation of peroxisome proliferator-activated receptor α (PPARα) in the brain to stimulate lysosomal biogenesis via TFEB. Accordingly, treadmill exercise remains unable to stimulate TFEB and reduce α-synucleinopathy in A53T mice lacking PPARα, and fenofibrate, a prototype PPARα agonist, reduces α-synucleinopathy. These results delineate a beneficial function of treadmill exercise in reducing α-syn spreading in the brain via PPARα.
10.1016/j.celrep.2022.111058