Review articleThe benefits and mechanisms of exercise training for Parkinson's disease
Graphical abstract
Introduction
Parkinson's disease (PD), a progressive neurodegenerative disorder, is mainly associated with many factors [1]. First, the strongest genetic risk factor of PD is a mutation in the gene encoding β-glucocerebrosidase [2]. According to previous studies, mutations of the LRRK2 gene have been found in familial and sporadic PD, and mutations of the SNCA gene (the alpha-synuclein gene) are regarded as risk factors for PD [3,4]. Furthermore, the influence of environmental factors on genetically susceptible persons plays a crucial role in the process of PD development [5]. For instance, xenobiotic exposure, such as transitional metal deposits going into vulnerable central nervous system areas, seems to interact with the genes which are regarded as risk factors for PD [5]. In addition, central nervous system infection and craniocerebral trauma, as well as exposure to pesticides and fungicides, such as rotenone and paraquat, seem to be associated with the pathological process of PD [[6], [7], [8]].
PD mainly occurs in adults who are 60 years or older, and its occurrence in men is higher than in women [9,10]. As the second most common neurodegenerative disorder, PD impacts at least 6 million people worldwide [11]. PD patients have motor and nonmotor disorders that prevent them from participating in exercise activities [12]. Motor disorders have received more attention from researchers and clinicians [13] and major motor symptoms include tremor, bradykinesia (hypokinesia or akinesia), plastic-type muscular rigidity and postural instability [14]. PD patients also have other kinds of typical motor disorders, including frozen gait, altered gait patterns and motor coordination dysfunctions [15]. Besides motor symptoms, nonmotor symptoms also influence quality of life and can include cognitive dysfunction, sleep disorder, anxiety, depression and fatigue [16]. There is an increasing amount of evidence indicating that nonmotor disorders can significantly affect quality of life, lead to disability, and cause more health-associated problems compared with a motor disorder [17]. There are also other types of symptoms that seriously affect the quality of life in PD patients, including loss of energy, negative emotions, and loss of control over one's own health [18,19]. Above all, the dysfunction caused by PD makes patients lose the ability to perform daily life activities and hence lose their independence [20].
Clinically, there are two types of treatments for PD: surgical therapy (deep brain stimulation) and medication (levodopa, dopamine agonists) [21]. l-dopa, the gold standard medication for PD motor symptoms, is a precursor of dopamine that can easily pass through the blood–brain barrier [14]. Other medications are also available, which are commonly related to L-dopa, and are classified in line with the mechanism of action so as to increase dopamine generation; these medications include catechol-o-methyl transferase (COMT) inhibitors, monoamine oxidase-B (MAO-B), and dopaminergic agonists for instance pramipexole (amantadine) [22]. Pharmacological therapy can improve PD patients' motor symptoms, but over time, the effect of dopaminergic treatments gradually diminishes, and several characteristics of motor control are resistant to pharmacological therapy [23]. Additionally, the existing medication treatments can only relieve symptoms and hence are unable to stop disease progression [24]. In recent years, two novel treatments for PD patients have emerged, including neurotrophic factor treatment and cell transplantation, but these two strategies mainly depend on highly invasive stereotaxic surgery that is accompanied by safety problems and side effects [25]. Under these circumstances, exercise, as a complementary and nonpharmacological therapy, is gaining more and more attention for the treatment of PD [26].
In 1992, Sasco et al. first reported a link between exercise and PD, and they found that exercise intervention in adulthood significantly reduced the risk of developing PD for the rest of one's lifetime [27]. Subsequently, several large-scale epidemiological research studies confirmed this beneficial role of exercise for PD [28,29]. Furthermore, Lau et al. indicated that exercise can potentially decrease the risk of worsening neurological deficits in PD [30]. As a complementary and alternative treatment, exercise can both improve the motor and nonmotor symptoms of PD patients [31]. In clinical studies, various types of exercise training, such as aerobic exercise, gait training, balance training, progressive resistance training and complementary exercise, have been used. In this review, we summarise the roles of different types of exercise training for PD patients and the related mechanisms in providing PD patients with an optimised exercise therapy and how this can delay disease progression and improve quality of life, thus benefiting the increasing number of PD patients.
Section snippets
Dysfunctions of PD
PD patients have both motor and nonmotor dysfunctions that prevent them from performing normal daily activities, and four of these dysfunctions are most common, including postural instability, gait disorder, freezing of gait, and cognitive impairments.
The involved mechanisms of exercise training in animal experiments
In recent years, researchers have conducted a series of studies to investigate the mechanisms of exercise training for PD. According to animal research, aerobic exercise exerts neurorestorative and neuroprotective effects, possibly through regulating neurotrophic factors to support synapse formation and angiogenesis, inhibiting oxidative stress and improving mitochondrial function [75]. For instance, exercise on a treadmill can increase the level of brain-derived neurotrophic factor (BDNF) and
Conclusion
Overall, various types of exercise therapy have been reported as having therapeutic effects on motor disorders and nonmotor disorders in patients with PD. Among the different kinds of exercise interventions, aerobic exercise is the most widely studied treatment and has positive effects on motor, quality of life, cognition and emotion. In addition, some new types of techniques have been used in the treatment of PD. For instance, VR technology provides patients with visual, auditory and
Declaration of competing interest
The authors declare no conflicts of interest.
References (171)
- et al.
Parkinson’s disease
Lancet (London, England)
(2015) - et al.
Prevalence and treatment of non-motor symptoms in Parkinson’s disease
Parkinsonism Relat. Disord.
(2007) - et al.
Psychosis, apathy, depression and anxiety in Parkinson’s disease
Neurobiol. Dis.
(2012) - et al.
Emerging therapies for Parkinson’s disease: from bench to bedside
Pharmacol. Ther.
(2014) - et al.
Exercise as a therapeutic intervention for motor and non-motor symptoms in Parkinson’s disease: evidence from rodent models
Prog. Neurobiol.
(2019) - et al.
Progressive resistance exercise improves strength and physical performance in people with mild to moderate Parkinson’s disease: a systematic review
J. Phys.
(2013) - et al.
Effects of exercise on gait and motor imagery in people with Parkinson disease and freezing of gait
Parkinsonism Relat. Disord.
(2018) - et al.
Walking capacity in mild to moderate Parkinson’s disease
Arch. Phys. Med. Rehabil.
(2006) Mild cognitive impairment is common in Parkinson’s disease patients with normal mini-mental state examination (MMSE) scores
Parkinsonism Relat. Disord.
(2009)Motor dual-tasking deficits predict falls in Parkinson’s disease: a prospective study
Parkinsonism Relat. Disord.
(2016)
The impact of Parkinson’s disease on sequence learning: perceptual pattern learning and executive function
Brain Cogn.
Dual-task-related neural connectivity changes in patients with Parkinson' disease
Neuroscience
Advances in the pharmacological treatment of Parkinson’s disease: targeting neurotransmitter systems
Trends Neurosci.
A convergent model for cognitive dysfunctions in Parkinson's disease: the critical dopamine-acetylcholine synaptic balance
The Lancet. Neurology
Peripheral cytokines profile in Parkinson’s disease
Brain Behav. Immun.
Pathogenesis-targeted, disease-modifying therapies in Parkinson disease
Neurotherapeutics: The Journal of the American Society for Experimental NeuroTherapeutics
Triggering endogenous neuroprotective processes through exercise in models of dopamine deficiency
Parkinsonism Relat. Disord.
Exercise exerts neuroprotective effects on Parkinson’s disease model of rats
Brain Res.
Treadmill exercise activates Nrf2 antioxidant system to protect the nigrostriatal dopaminergic neurons from MPP+ toxicity
Exp. Neurol.
Study on effect of striatal mGluR2/3 in alleviating motor dysfunction in rat PD model treated by exercise therapy
Front. Aging Neurosci.
Physical training exerts neuroprotective effects in the regulation of neurochemical factors in an animal model of Parkinson's disease
Neuroscience
The effect of exercise training in improving motor performance and corticomotor excitability in people with early Parkinson’s disease
Arch. Phys. Med. Rehabil.
Enhancing both motor and cognitive functioning in Parkinson’s disease: aerobic exercise as a rehabilitative intervention
Brain Cogn.
Influence of aerobic exercise training on the neural correlates of motor learning in Parkinson's disease individuals
Neuroimage Clin
Biomedicine. Parkinson’s–divergent causes, convergent mechanisms
Science (New York, N.Y.)
Multicenter analysis of glucocerebrosidase mutations in Parkinson’s disease
N. Engl. J. Med.
Type and frequency of mutations in the LRRK2 gene in familial and sporadic Parkinson's disease
Brain: a journal of neurology
The genetic background of Parkinson’s disease: current progress and future prospects
Acta Neurol. Scand.
Prevention of progression in Parkinson’s disease
Biometals
Head injury and Parkinson's disease: a population-based study
Movement disorders: official journal of the Movement Disorder Society
CNS infections, sepsis and risk of Parkinson’s disease
Int. J. Epidemiol.
Rotenone, paraquat, and Parkinson’s disease
Environ. Health Perspect.
Effects of a group protocol on physical activity and associated changes in mood and health locus of control in adults with Parkinson disease and reduced mobility
Perm J
Epidemiology and etiology of Parkinson’s disease: a review of the evidence
Eur. J. Epidemiol.
A tandem cycling program: feasibility and physical performance outcomes in people with Parkinson disease
Journal of Neurologic Physical Therapy: JNPT
Effects of qigong exercise on non-motor symptoms and inflammatory status in Parkinson’s disease: a protocol for a randomized controlled trial
Medicines (Basel)
Physical exercise for Parkinson’s disease: clinical and experimental evidence
Clin. Pract. Epidemiol. Ment. Health
Parkinson’s disease: clinical features and diagnosis
J. Neurol. Neurosurg. Psychiatry
Health-related quality of life in early Parkinson’s disease: the impact of nonmotor symptoms
Movement Disorders: Official Journal of the Movement Disorder Society
Quantifying the profile and progression of impairments, activity, participation, and quality of life in people with Parkinson disease: protocol for a prospective cohort study
BMC Geriatr.
A 12-week cycling training regimen improves upper limb functions in people with Parkinson’s disease
Front. Hum. Neurosci.
The Movement Disorder Society evidence-based medicine review update: treatments for the motor symptoms of Parkinson’s disease
Movement Disorders: Official Journal of the Movement Disorder Society
Progression of gait dysfunction in incident Parkinson’s disease: impact of medication and phenotype
Movement Disorders: Official Journal of the Movement Disorder Society
Effects of exercise on mobility in people with Parkinson’s disease
Movement Disorders: Official Journal of the Movement Disorder Society
The role of physical exercise in the occurrence of Parkinson’s disease
Arch. Neurol.
Physical activities and future risk of Parkinson disease
Neurology
Physical activity and risk of Parkinson's disease in the Swedish National March Cohort
Brain: a journal of neurology
Neuroprotective effects and mechanisms of exercise in a chronic mouse model of Parkinson’s disease with moderate neurodegeneration
Eur. J. Neurosci.
The effectiveness of exercise interventions for people with Parkinson’s disease: a systematic review and meta-analysis
Movement Disorders: Official Journal of the Movement Disorder Society
Cited by (91)
Exercise and gait/movement analyses in treatment and diagnosis of Parkinson's Disease
2024, Ageing Research ReviewsEffects of three physical exercise modalities on respiratory function of older adults with Parkinson's disease: A randomized clinical trial
2023, Journal of Bodywork and Movement TherapiesExercise training has a protective effect in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mice model with improved neural and intestinal pathology and modified intestinal flora
2023, Behavioural Brain ResearchCitation Excerpt :Therefore, regulation of the intestinal flora may be a good perspective to develop therapeutic approaches for PD. It is now recognized that different types of exercise training have a significant effect on motor disorders and non-motor disorders and improve the degeneration of the central nervous system [19]. However, different exercise interventions affect gut microbes differently [20].