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Exercise-Induced Neuroplasticity in Human Parkinson’s disease: What is the Evidence Telling Us?
... Physical exercise has been recommended since the times of Hippocrates and Galen as a general measure for health and disease prevention (27), but its mechanism has been completely unknown for centuries. At present, some of the potential mechanisms have been studied both in experimental animal models (28)(29)(30), and in patients with neurodegenerative diseases as well as controls (31)(32)(33)(34). ...
... Potential mechanisms include neuronal survival and plasticity, neurogenesis, epigenetic modifications, angiogenesis, autophagy, and the synthesis and release of neurotrophins (28)(29)(30)(31)(32)(33)(34)(35). ...
... Possibly, the most interesting and testable mechanism includes the release of Brain Derived Neurotrophic Factor (BDNF) (28)(29)(30)(31)(32)(33)(34), suffice is to recall that BDNF is a crucial neurotrophic factor with multiple roles on regulation of neurophysiological processes (35), including survival of striatal neurons (36). Physical exercise increases plasma BDNF levels in individuals with neurodegenerative disorders (34); and interestingly, BDNF receptor blockade prevents the beneficial effects of exercise in animal models (29). ...
... and as an adjunct to levodopa treatment (Fox et al., 2011). There is a growing body of evidence in support of PA and exercise interventions for producing an array of positive effects in PwPD, including improvements in motor and cognitive functions, anxiety and health related quality of life (HRQOL) (Ahlskog, 2011(Ahlskog, , 2018Bloem, de Vries, & Ebersbach, 2015;Foltynie & Langston, 2018;Hirsch, Iyer, & Sanjak, 2016;Kwok et al., 2019;Lauzé, Daneault, & Duval, 2016;Petzinger et al., 2016;Schenkman et al., 2018). In addition, PA is recommended as a secondary prevention approach to injury prevention and health promotion to delay onset and slow progression of disability (Rimmer & Lai, 2017) and to reduce risk of cognitive decline (Geneva: World Health Organization, 2019). ...
... Exercise programs are important for early implementation given their capability to affect brain structure and function, induce neuroplasticity changes, and improve motor symptoms (Hirsch et al., 2016;LaHue et al., 2016;Schenkman et al., 2018). In addition, exercise can improve non-motor symptoms, including cognition, mood, and sleep, which can appear years before motor symptoms (Reynolds et al., 2016). ...
... There is a wide array of positive effects that come when people with PD (PwPD) engage in PA, including improvements in impairments in body functions and structures (motor and mental functions, and PD clinical symptom presentation), and in activity limitations (occupational performance in ADLs and instrumental activities of daily living (IADLs) (Goodwin, Richards, Taylor, Taylor, & Campbell, 2008;Lauzé et al., 2016;Sturkenboom et al., 2011). Aerobic exercise has also been shown to have effects on brain structure and function in PD (Ahlskog, 2018;Fisher et al., 2013;Hirsch et al., 2016;Hou et al., 2017;Petzinger et al., 2016). Although there is a growing body of evidence in support of the positive effects of PA in these areas, it is unclear how PA engagement affects participation, and in particular occupational performance in other areas such as work, leisure, and social life (LaHue et al., 2016). ...
PURPOSE Parkinson’s Disease (PD) is a progressive neurodegenerative disorder. Engagement in exercise and physical activity (PA) produce positive effects in people with PD (PwPD), including improvements in motor and cognitive functions. PwPD are 1/3 less active than healthy adults and PA levels decline. Study aim was to evaluate feasibility, acceptability and preliminary efficacy for PA levels, self-efficacy, motivation, and self-perception of performance.
DESIGN: Single arm cohort feasibility study was conducted over 4 months. An occupational therapist (OT) delivered 6 individual (remote or in-person) sessions to provide directed support regarding PA and exercise habits, with check-ins on the other weeks.
METHOD: Sessions utilized workbook-based approach to provide disease-specific education and guide goal setting. Fitbit Charge 2 devices were provided to track progress towards goals and to facilitate therapist coaching. Outcome measures included retention and adherence rates, implementation fidelity, intervention acceptability (TFA questionnaire and PAS-HCCQ), PA levels, time spent in planned versus unplanned activity (Brunel), exercise motivation (BREQ-2), self-efficacy (Norman scale), and perception of and satisfaction with active recreation (mCOPM). Mean differences (post-pre) were calculated for each participant for each measure and then a group mean change with 95% CI, as well as Cohen’s d to calculate effect size.
RESULTS: 61 individuals were contacted. 13 participants with Hoehn and Yahr (H&Y) Stages I-II (mean (SD) age = 61.69 (9.14)) were enrolled. 92% of participants completed all 6 sessions. Intervention delivery had high fidelity and acceptability. Post-intervention improvements seen in self-efficacy (MD = 5.55; 95% CI -1.74-12.74; d = 0.33); identified regulation of motivation (MD = 0.21; 95% CI -0.14-0.55; d = 0.48); planned PA (MD =; 95% CI -0.28-0.98; d = 0.45); and % time in MVPA (MD = 0.79%; 95% CI 0.62-2.38; d = 0.49). Significant improvement in perceptions of performance (MD = 3.09; 95% CI 2.12-4.06; d = 1.63) and satisfaction (MD = .58; 95% CI 1.72-4.06; d = 1.63).
CONCLUSION: Findings suggest Pre-Active PD is feasible and acceptable for PwPD H&Y stage I-II, and may improve exercise levels, self-efficacy, motivation, and planned PA. Future research needed to address limitations and evaluate comparative effectiveness in larger sample size.
... Exercise increases neuroprotection in animal models through biological mechanisms such as preventing the loss of dopamine cells and increasing neurotrophic factors [19][20][21]. It is considered neurorestorative because it has been shown to downregulate dopamine transporter thus increasing dopamine in the extracellular space [22], particularly important for PwPD who exhibit decreased dopamine levels [18,22]. Increased cerebral blood flow, which increases angiogenesis and altered blood brain barrier permeability, is one example of how exercise may provide a component of neuroprotection and promote general brain health [18,20,23]. ...
... Exercise increases neuroprotection in animal models through biological mechanisms such as preventing the loss of dopamine cells and increasing neurotrophic factors [19][20][21]. It is considered neurorestorative because it has been shown to downregulate dopamine transporter thus increasing dopamine in the extracellular space [22], particularly important for PwPD who exhibit decreased dopamine levels [18,22]. Increased cerebral blood flow, which increases angiogenesis and altered blood brain barrier permeability, is one example of how exercise may provide a component of neuroprotection and promote general brain health [18,20,23]. ...
Introduction
The purpose of this study was to evaluate change in motor function, gait speed, dynamic balance, balance confidence, and quality of life (QoL) in nine participants with Parkinson's disease (PwPD) completing Lee Silverman Voice Treatment BIG (LSVT-BIG), an external cueing and task-based intervention. Although supported as an efficacious treatment in PwPD, there is limited research examining clinically meaningful change in outcome measures related to external cueing and task-based interventions.
Materials and Methods
This was a case series of nine PwPD (age range 64-76 years, 55% male) who completed the LSVT-BIG protocol. Disease duration ranged from 1 to 17 years and was classified as moderate in all participants (Hoehn and Yahr = 2 or 3). Outcome measures included motor function (MDS-UPDRS Part III Motor), gait speed, dynamic balance (MiniBEST), Activities-specific Balance Confidence (ABC), and Summary Index for PD Quality of Life 39 (PDQ-SI). Assessments were completed at baseline (BASE), end of treatment (EOT), and 4 weeks after EOT (EOT+4).
Results
Minimal detectable change (MDC) or minimal clinical important difference (MCID) was observed in one or more outcome measures in 8 of 9 participants at EOT and EOT+4 across domains of motor function (67%, 78%), gait speed (78%, 67%), balance confidence (44%, 33%), quality of life (44%, 78%), and dynamic balance (22%, 22%). Discussion. In this case series, 8 of 9 participants showed MDC or MCID changes across multiple functional domains. Improvements were observed immediately post (EOT) and 4-week post-treatment (EOT+4) suggesting a temporal component of the LSVT-BIG impact on functional change. Future research should include clinical trials to examine additional external cueing and task-based intervention efficacy with consideration of intensity, frequency, and mode of delivery across disease severity.
... 6 Thus, several non-pharmacological therapies have been used to control disease symptoms, which consequently help maintain independence level and QoL of individuals with PD. 1,7,8 Among the therapies for Parkinson's disease (PD), physical exercise has been described as a stimulus for the synthesis of endogenous neurotrophic factors such as glutamate receptors and neurotrophic factors including insulinlike growth factor 1 (IGF-1), vascular endothelial growth factor (VEGF), cerebral dopaminergic neurotrophic factor (CDNF), brain-derived neurotrophic factor (BDNF), and glia cell line-derived neurotrophic factor (GDNF). 9 Aquatic training has been increasingly used for physical rehabilitation in professional practice. Although some studies have analyzed the effects of aquatic training on the treatment of PD and other neurodegenerative diseases, 1,10,11 little detailed research has been done on the advantages, disadvantages, and precautions related to the practice of this physical activity. ...
... This enhances integration between balance and coordination systems, which may favor the individuals' neuroplasticity. 9 Regarding the PDQ-39 scale, which is used to evaluate QoL of individuals with PD, the results obtained did not show significant values after the training program. However, a greater decrease on the averages of the EG when compared to the CG was observed; thus, indicating a higher QoL reported by the individuals assessed. ...
Objectives
Parkinson’s disease (PD) is a neurodegenerative disorder that impacts the dopaminergic neurons of the substantia nigra, leading to motor and non-motor symptoms, as well as changes in activities of daily living (ADL) and quality of life (QoL). Aquatic physical exercises and dual-task physical exercises have been used to manage PD symptoms. The aim of this study was to investigate the effects of a dual-task aquatic exercise program on the ADL, motor symptoms, and QoL of individuals with PD.
Methods
A randomized controlled trial with a parallel group design was employed, and participants were randomized into 2 groups: a control group and an experimental group. The intervention was a 10-week program consisting of twice-weekly 40-minute aquatic dual-task exercises. Pre-intervention evaluations of ADL, motor function, and QoL were conducted at baseline (AS1), immediately after the intervention (AS2), and 3 months post-intervention (follow-up—AS3). The Unified Parkinson’s Disease Rating Scale (UPDRS) II and III sections and the Parkinson’s Disease Questionnaire 39 (PDQ-39) were utilized for outcome measures.
Results
A total of 25 individuals completed the study. The experimental group showed significant improvements in both the UPDRS II (ADL) and III (motor function) sections ( P’s < .05), but there was no significant difference in PDQ-39 scores. Additionally, significant differences were observed in the experimental group between the AS2 and AS3 time periods ( P < .05) for both UPDRS II and III scores ( P < .05).
Conclusions
Aquatic dual-task training may be effective in improving both ADL and motor functions in individuals with PD. Furthermore, the combination of aquatic environment and dual-task exercises may represent a promising approach to maintaining and improving the functionality of individuals with PD.
... Because of this reason, it is necessary to assess the effectiveness of other treatment methods. Although PD is progressive in nature, physical exercises is an important element in the rehabilitation of patients with PD for improving or maintaining function and slowing the disease progression [10][11][12][13][14]. Previous studies have reported the positive effect of stretching and resistance training in patients with PD [10][11][12]. ...
... Because of this reason, it is necessary to assess the effectiveness of other treatment methods. Although PD is progressive in nature, physical exercises is an important element in the rehabilitation of patients with PD for improving or maintaining function and slowing the disease progression [10][11][12][13][14]. Previous studies have reported the positive effect of stretching and resistance training in patients with PD [10][11][12]. Besides, numerous studies have demonstrated that mind-body exercises (MBE) (Tai-chi, Qigong, yoga, Pilates, and dance) were complementary to traditional therapy and considered as a potentially promising approach for conquering PD [9,15]. ...
Background
Several studies have investigated the effect of mind–body exercise (MBE) on functional performance and health-related quality of life (HRQoL) in Parkinson’s disease (PD), but it is still very difficult for clinicians to make informed decision on the best mind–body exercise for PD.PurposeWe analyzed the relative efficacy of MBE (yoga, Tai-Chi, Pilates, Qigong, and dance) in improving functional performance and HRQoL in patients with PD.MethodsA systematic review of randomized controlled trials (RCTs) was performed using network meta-analysis (NMA), searching the following databases: Cochrane, Web of Science, and PubMed using specific keywords until December 28, 2021, assessing the effects of MBE on functional performance and HRQoL in patients with PD.ResultsThis review included 60 RCTs with 2037 participants. A ranking of MBE for modifying various aspects of functional performance and HRQoL was achieved. Pairwise NMA showed Pilates to be the most effective in improving functional mobility (MD: − 3.81; 95% CI (− 1.55, − 6.07) and balance performance (SMD: 2.83; 95% CI (1.87, 3.78). Yoga (MD: − 5.95; 95% CI (− 8.73, − 3.16) and dance (MD: − 5.87; 95% CI (− 8.73, − 3.01) to be the most effective in improving motor function, whereas Qigong (MD: 0.32; 95% CI (0.00, 0.64) was most effective in improving gait speed. Considering HRQoL, dance was found to be the most effective (SMD: − 0.36; 95% CI (− 0.70, -0.01).ConclusionMBE should be considered an effective strategy for improving functional performance and HRQoL in patients with PD. The most effective MBE intervention varied with the functional performance domain. Dance was an effective exercise for improving HRQoL among people with PD.PROSPERO registration IDCRD42022301030.
... In limb motor control, an increasing number of studies have evaluated activity-based methods for inducing neuroplastic changes to enhance limb motor recovery through dynamic or sustained motor activity. The therapeutic benefits of continuous motor activity on limb motor function has been demonstrated in both healthy individuals and in individuals with neurologic diseases (Fisher et al. 2008;Hirsch et al. 2016;Petzinger et al. 2013). For example, Fisher et al. (2008) found that a treadmill training exercise protocol both modified cortical excitability and improved parameters of gait (i.e., speed, stride length, weight distribution, etc.) in participants with Parkinson's disease (PD). ...
... Our hypothesis was that neuroplastic changes induced by continuous chewing and speech prior to the nonword repetition task would impact subsequent speech performance and be associated with reduced inhibition, as measured by TMS. The context for this study is the emerging literature suggesting that sustained motor activities induce neuroplastic changes that support learning and motor rehabilitation (Fisher et al. 2008;Hirsch et al. 2016;Petzinger et al. 2013). The primary findings of this work were the following: (1) speech accuracy and performance improved significantly across repetitions of the novel speech motor learning task; (2) speech accuracy and performance during the nonword repetition task was enhanced when it followed 10 min of continuous chewing; (3) in contrast, speech accuracy and performance was degraded when it followed 10 min of continuous talking; and (4) condition effects on task performance were not associated with detectible changes in cortical excitability as measured by the cSP of lip motor cortex. ...
Sustained limb motor activity has been used as a therapeutic tool for improving rehabilitation outcomes and is thought to be mediated by neuroplastic changes associated with activity-induced cortical excitability. Although prior research has reported enhancing effects of continuous chewing and swallowing activity on learning, the potential beneficial effects of sustained oromotor activity on speech improvements is not well-documented. This exploratory study was designed to examine the effects of continuous oromotor activity on subsequent speech learning. Twenty neurologically healthy young adults engaged in periods of continuous chewing and speech after which they completed a novel speech motor learning task. The motor learning task was designed to elicit improvements in accuracy and efficiency of speech performance across repetitions of eight-syllable nonwords. In addition, transcranial magnetic stimulation was used to measure the cortical silent period (cSP) of the lip motor cortex before and after the periods of continuous oromotor behaviors. All repetitions of the nonword task were recorded acoustically and kinematically using a three-dimensional motion capture system. Productions were analyzed for accuracy and duration, as well as lip movement distance and speed. A control condition estimated baseline improvement rates in speech performance. Results revealed improved speech performance following 10 min of chewing. In contrast, speech performance following 10 min of continuous speech was degraded. There was no change in the cSP as a result of either oromotor activity. The clinical implications of these findings are discussed in the context of speech rehabilitation and neuromodulation.
... Animal studies suggest that exercise may induce neuroplastic changes in PD [7][8][9][10], but only a few studies have been conducted on humans with PD. A handful of reviews have reported on this topic previously [3,4,[11][12][13], but only one was conducted and reported in a systematic manner [4]. Further, they either included both human and animal studies [3,[11][12][13] or focused on one neuroplastic outcome only [4]. ...
... A handful of reviews have reported on this topic previously [3,4,[11][12][13], but only one was conducted and reported in a systematic manner [4]. Further, they either included both human and animal studies [3,[11][12][13] or focused on one neuroplastic outcome only [4]. ...
Parkinson’s disease (PD) is a neurodegenerative disorder for which there is currently only symptomatic treatment. During the last decade, there has been an increased interest in investigating physical exercise as a neuroprotective mechanism in PD. Animal studies have suggested that exercise may in fact induce neuroplastic changes, but evidence in humans is still scarce. A handful of reviews have previously reported on exercise-induced neuroplasticity in humans with PD, but few have been systematic, or have mixed studies on both animals and humans, or focused on one neuroplastic outcome only. Here, we provide a systematic review and metasynthesis of the published studies on humans in this research field where we have also included different methods of evaluating neuroplasticity. Our results indicate that various forms of physical exercise may lead to changes in various markers of neuroplasticity. A narrative synthesis suggests that brain function and structure can be altered in a positive direction after an exercise period, whereas a meta-analysis on neurochemical adaptations after exercise points in disparate directions. Finally, a GRADE analysis showed that the current overall level of evidence for exercise-induced neuroplasticity in people with PD is very low. Our results demonstrate that even though the results in this area point in a positive direction, researchers need to provide studies of higher quality using more rigorous methodology.
... Acupuncture [36][37][38] and exercise [39,40] have both been shown in recent studies to have potential neuroplastic and neuroprotective effects in PD Prior to this study, we established a complex therapy (MARS-PD) to enhance the synergistic effects of acupuncture and exercise [16]. The goal of this randomized controlled trial is to assess MARS-PD's clinical efficacy, safety, and cost-effectiveness. ...
Background
Parkinson’s disease (PD) patients face a substantial unmet need for disease-modifying interventions. Potential approaches such as exercise and acupuncture have been investigated to slow PD progression. To address this unmet need, we developed a novel therapeutic approach that integrates acupuncture and exercise: the Meridian Activation Remedy System for PD patients (MARS-PD). Building upon promising outcomes observed in our preliminary pilot study, where MARS-PD exhibited a large clinically important difference on the Movement Disorder Society Unified Parkinson’s Disease Rating Scale Part III (MDS-UPDRS Part III), we embark on a randomized controlled trial with the primary objective of examining the efficacy, safety, and economic impact of MARS-PD.
Methods
In this single-center, assessor and statistician-blinded, parallel-group randomized controlled trial, we aim to investigate the clinical efficacy of MARS-PD through 16 interventions administered over 8 weeks in 88 PD patients. Participants will be randomly assigned to the experimental (n = 44) or control (n = 44) groups. The experimental group will receive MARS-PD intervention alongside standard care, while the control group will solely receive standard care. The intervention period spans 8 weeks, followed by a 12-week post-intervention follow-up. The primary endpoint is the change in MDS-UPDRS Part III score from baseline to the conclusion of the 8-week intervention. Secondary outcomes encompass various assessments, including MDS-UPDRS, International Physical Activity Questionnaire Short Form, Parkinson Self Questionnaire, Parkinson’s Disease Sleep Scale, Timed Up and Go test, GAITRite metrics, Functional Near-Infrared Spectroscopy measurements, smart band outcomes, gut microbiome analysis results, and iris connective tissue texture.
Discussion
Previous studies by the authors have indicated MARS-PD’s safety and benefits for PD patients. Building upon this foundation, our current study aims to provide a more comprehensive and detailed confirmation of the efficacy of MARS-PD.
Trial registration
cris.nih.go.kr KCT0006646 –First posted on 7 October 2021; ClinicalTrials.gov NCT05621772 –First posted on 11 November 2022.
... Physical activity (PA) has been hailed as "the new medicine" for Parkinson's; PA is no longer viewed as a complementary intervention, but of equal importance to medication [9]. The interest in PA has been fuelled by the association between PA and the reduced risk of developing Parkinson's [10] and the potential to attenuate symptom progression [11,12]. Systematic reviews highlight that PA results in improved strength, balance, gait, and physical capacity [13][14][15][16], as well as improved motor and non-motor symptoms [17][18][19][20][21][22]. ...
Research has shown that physical activity has a range of benefits for people living with Parkinson’s (PLwP), improving muscle strength, balance, flexibility, and walking, as well as non-motor symptoms such as mood. Parkinson’s Beats is a form of cardio-drumming, specifically adapted for PLwP, and requires no previous experience nor skills. Nineteen PLwP (aged between 55 and 80) took part in the regular Parkinson’s Beats sessions in-person or online. Focus group discussions took place after twelve weeks to understand the impacts of Parkinson’s Beats. Through the framework analysis, six themes and fifteen subthemes were generated. Participants reported a range of benefits of cardio-drumming, including improved fitness and movement, positive mood, the flow experience, and enhanced social wellbeing. A few barriers to participation were also reported. Future research is justified, and best practice guidelines are needed to inform healthcare professionals, PLwP and their care givers.
... Kempermann et al. (2018) demonstrated that an increase in neurotrophins, such as BDNF, results in an increase in neuroplasticity [62]. Because of this finding, with the increases in BDNF following either acute or regular exercise [63], studies have found a potential correlation between exerciseinduced BDNF and increases in neuroplasticity [59,61,62,64]. For example, three cognitive rehabilitation sessions per week for one month in patients with PD involving paper and pencil exercises have shown improvements in serum BDNF levels and cognition [65]. ...
The growing incidence of Parkinson’s Disease (PD) is a major burden on the healthcare system. PD is caused by the degeneration of dopaminergic neurons and is known for its effects on motor function and sleep. Sleep is vital for maintaining proper homeostasis and clearing the brain of metabolic waste. Adequate time spent in each sleep stage can help maintain homeostatic function; however, patients with PD appear to exhibit sleep impairments. Although medications enhance the function of remaining dopaminergic neurons and reduce motor symptoms, their potential to improve sleep is still under question. Recently, research has shifted towards exercise protocols to help improve sleep in patients with PD. This review aims to provide an overview of how sleep is impaired in patients with PD, such as experiencing a reduction in time spent in slow-wave sleep, and how exercise can help restore normal sleep function. A PubMed search summarized the relevant research on the effects of aerobic and resistance exercise on sleep in patients with PD. Both high and low-intensity aerobic and resistance exercises, along with exercises related to balance and coordination, have been shown to improve some aspects of sleep. Neurochemically, sleeping leads to an increase in toxin clearance, including α-synuclein. Furthermore, exercise appears to enhance the concentration of brain-derived neurotrophic factors, which has preliminary evidence to suggest correlations to time spent in slow-wave sleep. More research is needed to further elucidate the physiological mechanism pertaining to sleep and exercise in patients with PD.
... The mechanisms for the functional benefits observed in our study are probably multiple and complex. Studies suggested that physiologic use of exercise can be an important component of neuroplastic changes in the human PD brain and support the central hypothesis that selfproduced activity is important in slowing, halting the symptoms of PD (Hirsch et al., 2016). Therefore, it is possible that these types of non-pharmacological interventions could preserve, or help restore motor and cognitive effectiveness in PD (Bherer et al., 2013). ...
... It is highly improbable as a result of calcium, fat, lactose, protein, or vitamin D. According to one hypothesis, milk consumption decreases uric acid and is hence hazardous [46]. Other potential pathways include changes in microbiota triggered by dairy foods or lactose intolerance, which might promote inflammatory responses in the intestine and porosity but which have yet to be properly investigated [47]. ...
Background: Parkinson's disease is a complicated, gradually progressive neurological illness characterized by locomotor and non-motor symptomatology that impedes daily activities. Despite significant advances in symptomatic therapies with various extents of negative effects, there are currently no disease-modifying medicinal alternatives. Symptoms worsen, creating an additional strain that reduces living quality and creates the perception that prescription drugs are no longer productive. Objective: Adopting healthy lifestyle habits can help patients feel more empowered, promote well-ness, relieve symptoms, and potentially slow neurodegeneration. Nutrition, intellectual stimulation, physical exercise, and stress reduction are all examples of lifestyle habits that improve cognitive health and life satisfaction. We discuss how changes in lifestyle, nutrition, yoga, exercise, and acupuncture can help with managing the disease's symptoms.
... It is highly improbable as a result of calcium, fat, lactose, protein, or vitamin D. According to one hypothesis, milk consumption decreases uric acid and is hence hazardous [46]. Other potential pathways include changes in microbiota triggered by dairy foods or lactose intolerance, which might promote inflammatory responses in the intestine and porosity but which have yet to be properly investigated [47]. ...
Background
Parkinson's disease is a complicated, gradually progressive neurological illness characterized by locomotor and non-motor symptomatology that impedes daily activities. Despite significant advances in symptomatic therapies with various extents of negative effects, there are currently no disease-modifying medicinal alternatives. Symptoms worsen, creating an additional strain that reduces living quality and creates the perception that prescription drugs are no longer productive.
Objective
Adopting healthy lifestyle habits can help patients feel more empowered, promote wellness, relieve symptoms, and potentially slow neurodegeneration. Nutrition, intellectual stimulation, physical exercise, and stress reduction are all examples of lifestyle habits that improve cognitive health and life satisfaction. We discuss how changes in lifestyle, nutrition, yoga, exercise, and acupuncture can help with managing the disease's symptoms.
Method
We searched Google Scholar for various research papers and review articles from publishers, such as Bentham Science, Elsevier, Taylor and Francis, Springer Nature, and others for gathering the data for the study.
Result
Pesticide exposure, environmental hazards, dietary choices, stress, and anxiety all have an indirect or immediate influence on the commencement of Parkinson's disease. Naturopathic remedies, such as nutraceuticals, yoga, exercise, and acupuncture, have been shown to help with Parkinson's disease management.
Conclusion
Various preclinical and clinical studies have shown that the various factors mentioned are beneficial in the management of the disease, but more research is needed to validate the extent to which such factors are beneficial.
... Research supports exercise-induced neuroplasticity through the enhancement of trophic factors (e.g., brain-derived neurotrophic factor [BDNF]), potentially slowing down PD progression and improving brain function [16,17]. Although there is evidence suggesting that both intervention and individual session duration may influence neurotrophic factor levels [18], brain structure and function [17], most studies in PwP have focused on short interventions (<12 weeks) without evaluating more chronic changes in BDNF, or comparing them to other populations (e.g., PwP that are non-exercisers or healthy adults) [19]. Hence, there is a need to develop long-term interventions and treatment regimes that elicit long-lasting benefits for PwP. ...
Introduction: Individuals with Parkinson’s Disease (PD) can develop a range of motor and non-motor symptoms
due to its progressive nature and lack of effective treatments. Exercise interventions, such as multimodal (MM)
programmes, may improve and sustain physical or cognitive function in PD. However, studies usually evaluate
physical performance, cognition, and neuroprotective biomarkers separately and over short observation periods.
Methods: Part one evaluates the effects of a weekly community-based MM exercise class (60 min) on physical
function in people with PD (PwP). Exercise participants (MM-EX; age 65 ± 9 years; Hoehn and Yahr (H&Y) scale
≤ IV) completed a battery of functional assessments every 4 months for one (n = 27), two (n = 20) and three
years (n = 15). In part two, cognition and brain-derived neurotrophic factor (BDNF) levels were assessed over 6-
to-8 months and compared to aged-matched non-active PwP (na-PD, n = 16; age 68 ± 7 years; H&Y scale ≤ III)
and healthy older adults (HOA, n = 18; age 61 ± 6 years).
Results: MM-EX significantly improved walking capacity (5% improvement after 8 months), functional mobility
(11% after 4 months), lower extremity strength (15% after 4 months) and bilateral grip strength (9% after 28
months), overall, maintaining physical function across 3 years. Group comparisons showed that only MM-EX
significantly improved their mobility, lower extremity strength, cognition and BDNF levels.
Conclusion: Weekly attendance to a community-based MM exercise group session can improve and maintain
physical and cognitive function in PD, with the potential to promote neuroprotection.
... Exercise is defined as a subcategory of physical activity and includes those activities that are planned, structured, repetitive, purposive in nature, and intended to improve one or more components of physical fitness [12]. However, in humans with PD, there is a paucity of evidence suggesting a neuroprotective effect of exercise [13]. Hence it was necessary to create application which was portable and user efficient. ...
National projections indicate that the number of people over 60 years old is expected to increase, bringing with it an increase in the number of people affected by Parkinson's Disease (PD). This makes PD an important public health problem. Therefore, the development of effective approaches for intervention in people with Parkinson's disease needs to be more thoroughly investigated. End-to-end application will make exercising at home more convenient for patients. We can project prescribed exercises and determine whether the patient is completing them correctly. The Flutter app enables patients to register themselves, communicate with specialists over the app, and make virtual appointments. The pose detection library will help us detect angles of the exercises, and determine whether patients are performing them correctly
... Self-selected training speed when overriding the motor's assistance was 10% faster during the VR-enhanced compared to the Non-VR condition, a finding expected to have important clinical implications. Research from the neurosciences has pointed to the importance of performing many step-like movements each day to not only improve walking, but also promote lasting neuroplastic change (Hirsch et al., 2016;Shimada et al., 2017). In the current study, the 10% faster training speed during VR-enhanced ICARE training equated to a similar increase in number of step-like movements compared to the Non-VR condition. ...
Virtual reality (VR) gaming is promising in sustaining children’s participation during intensive physical rehabilitation. This study investigated how integration of a custom active serious gaming with a robot-motorized elliptical impacted children’s perception of engagement (Intrinsic Motivation Inventory), physiologic effort (i.e., exercise speed, heart rate, lower extremity muscle activation), and joint kinematics while overriding the motor’s assistance. Compared to Non-VR condition, during the VR-enhanced condition participants’ perceived engagement was 23% greater ( p = 0.01), self-selected speed was 10% faster ( p = 0.02), heart rate was 7% higher ( p = 0.08) and muscle demands increased. Sagittal plane kinematics demonstrated only a small change at the knee. This study demonstrated that VR plays an essential role in promoting greater engagement and physiologic effort in children performing a cyclic locomotor rehabilitation task, without causing any adverse events or substantial disruption in lower extremity joint kinematics. The outcomes of this study provide a foundation for understanding the role of future VR-enhanced interventions and research studies that weigh/balance the need to physiologically challenge a child during training with the value of promoting task-related training to help promote recovery of walking.
... Another important aspect of lifestyle as a therapeutic option for targeting the microbiome is exercise, which was shown to decrease the risk for neurodegeneration, induce neurorestorative and neuroprotective effects, and modulate disease progression in animal and human observational studies [172,173]. In this respect, a variety of rodent model studies revealed alterations of the gut microbiome following different forms of exercise, in interaction with, but also independently from dietary changes [174,175]. ...
Neurodegenerative diseases such as Parkinson’s (PD) and Alzheimer’s disease (AD), the prevalence of which is rapidly rising due to an aging world population and westernization of lifestyles, are expected to put a strong socioeconomic burden on health systems worldwide. Clinical trials of therapies against PD and AD have only shown limited success so far. Therefore, research has extended its scope to a systems medicine point of view, with a particular focus on the gastrointestinal–brain axis as a potential main actor in disease development and progression. Microbiome and metabolome studies have already revealed important insights into disease mechanisms. Both the microbiome and metabolome can be easily manipulated by dietary and lifestyle interventions, and might thus offer novel, readily available therapeutic options to prevent the onset as well as the progression of PD and AD. This review summarizes our current knowledge on the interplay between microbiota, metabolites, and neurodegeneration along the gastrointestinal–brain axis. We further illustrate state-of-the art methods of microbiome and metabolome research as well as metabolic modeling that facilitate the identification of disease pathomechanisms. We conclude with therapeutic options to modulate microbiome composition to prevent or delay neurodegeneration and illustrate potential future research directions to fight PD and AD.
... Large prospective studies also show that the risk of PD is significantly reduced by midlife exercise [7,8]. In addition to neuroprotective benefits, there is an increasing body of evidence that exercise may promote neural plasticity and slow disease progression in PD [9][10][11]. There is some thought that exercise may also help non-motor symptoms of fatigue, depression, and cognition, although more studies are needed to clarify this. ...
... Another important aspect of lifestyle as a therapeutic option for targeting the microbiome is exercise which was shown to decrease the risk for neurodegeneration, induce neurorestorative and neuroprotective effects and modulate disease progression in animal and human observational studies [148,149]. In this respect, a variety of rodent model studies revealed alterations of the gut microbiome following different forms of exercise, in interaction with but also independently from dietary changes [150,151]. ...
Due to the aging of the world population and westernization of lifestyles, the prevalence of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD) is rapidly rising and is expected to put a strong socioeconomic burden on health systems worldwide. Due to the limited success of clinical trials of therapies against neurodegenerative diseases, research has extended its scope to a systems medicine point of view, with a particular focus on the gastrointestinal-brain axis as a potential main actor in disease development and progression. Microbiome as well as metabolome studies along the gastrointestinal-brain axis have already revealed important insights into disease pathomechanisms. Both the microbiome and metabolome can be easily manipulated by dietary and lifestyle interventions, and might thus offer novel, readily available therapeutic options to prevent the onset as well as the progression of PD and AD. This review summarizes our current knowledge on the association between microbiota, metabolites, and neurodegeneration in light of the gastrointestinal-brain axis. In this context, we also illustrate state-of-the art methods of microbiome and metabolome research as well as metabolic modeling that facilitate the identification of disease pathomechanisms. We conclude our review with therapeutic options to modulate microbiome composition to prevent or delay neurodegeneration and illustrate potential future research directions to fight PD and AD.
... [13]. Additionally, ET increases corticomotor excitability and the levels of brain-derived neurotrophic factor, and changes brain grey matter volume [14]. ...
Background
Evidence has demonstrated that endurance training (ET) reduces the motor signs of Parkinson’s disease (PD). However, there has not been a comprehensive meta-analysis of studies to date.
Objective
The aim of this study was to compare the effect of ET versus nonactive and active control conditions on motor signs as assessed by either the Unified Parkinson’s Disease Rating Scale part III (UPDRS-III) or Movement Disorder Society-UPDRS-III (MDS-UPDRS-III).
Methods
A random-effect meta-analysis model using standardized mean differences (Hedges’ g) determined treatment effects. Moderators (e.g., combined endurance and physical therapy training [CEPTT]) and meta-regressors (e.g., number of sessions) were used for sub-analyses. Methodological quality was assessed by the Physiotherapy Evidence Database.
Results
Twenty-seven randomized controlled trials (RCTs) met inclusion criteria (1152 participants). ET is effective in decreasing UPDRS-III scores when compared with nonactive and active control conditions (g = − 0.68 and g = − 0.33, respectively). This decrease was greater (within- and between-groups average of − 8.0 and − 6.8 point reduction on UPDRS-III scores, respectively) than the moderate range of clinically important changes to UPDRS-III scores (− 4.5 to − 6.7 points) suggested for PD. Although considerable heterogeneity was observed between RCTs (I² = 74%), some moderators that increased the effect of ET on motor signs decreased the heterogeneity of the analyses, such as CEPTT (I² = 21%), intensity based on treadmill speed (I² = 0%), self-perceived exertion rate (I² = 33%), and studies composed of individuals with PD and freezing of gait (I² = 0%). Meta-regression did not produce significant relationships between ET dosage and UPDRS-III scores.
Conclusions
ET is effective in decreasing UPDRS-III scores. Questions remain about the dose–response relationship between ET and reduction in motor signs.
... 27 Likewise, Hirsch et al. support the hypothesis that a balance and resistance training programme, carried out under appropriate supervision, is pleasant and effective and a relatively safe way to improve muscle strength and balance in individuals with Parkinson's; such a programme can also reduce the risk of falls in the home and in the comunity, with a greater likelihood of long-term independence. 28 The +Model K. Palheta de Lima, C. Nascimento da Silva, N. Ferreira de Seixas et al. objective of the study was to evaluate the immediate shortterm effects of 2 exercise programmes and establish how a specific rehabilitation programme could affect the muscle strength and balance in individuals with Parkinson's. When the core deficit of each patient with Parkinson's is analysed, the physiopathology of the disease also has to be considered so that the most coherent intervention is used. ...
Background
Physical exercise has contributed significantly to the quality of life of the population. Therefore, countless specialists have established relationships between t people who perform physical exercise and success in the treatment of diseases, such as Parkinson’s disease in older adults.
Objective
The aim of this research is to analyse the influence of resistance training in the correlation of balance and postural control in people with Parkinson’s disease.
Method
A systematic review was conducted according to the recommendations of the Preferred Reporting Items for Systematic Reviews And Meta-Analyses (PRISMA), in consultation with the PubMed, Scielo, BVS (Lilacs), ScienceDirect and Cochrane databases, based on the influence of resistance training on postural balance and control in older adults with Parkinson’s disease, highlighting as the main assessment tool the Movement Disorders Society — Unified Parkinson’s Disease Rating Scale.
Results
After searching the selected databases and considering the inclusion and exclusion criteria of this study, 10 studies were selected to compose this review and a total of 556 participants were pooled. It was observed that most of the interventions (60%) had a duration of approximately 30−45 min over eight to twelve weeks, the most used measuring instruments were the BESTest (Balance Evaluation System Test), FOG-Q (Freezing of Gait Questionnaire) and the MDS-UPDRS (Movement Disorders Society-Unified Parkinson’s Disease Rating Scale).
Conclusion
Physical exercise plays a fundamental role in the intervention and prevention of Parkinson’s disease symptoms with regard to balance, strength, and quality of life.
... Asimismo, Hirsch et al. (2016) argumentaron que la hipótesis de un programa de entrenamiento de equilibrio y resistencia, realizado bajo una supervisión adecuada, es efectivo y placentero, es una forma relativamente segura de mejorar la fuerza muscular y el equilibrio en personas con párkinson y puede reducir el riesgo de caídas en el hogar y en la comunidad, con una mayor probabilidad de independencia a largo plazo 28 . El estudio tuvo como objetivo evaluar los efectos inmediatos a corto plazo de 2 programas de ejercicio y determinar cómo un programa de rehabilitación específico puede influir en la fuerza muscular y el equilibrio en personas con párkinson. ...
Resumen
Introducción
La práctica de ejercicio físico ha contribuido significativamente a la calidad de vida de la población, por ello, innumerables especialistas han establecido relaciones entre los practicantes de ejercicio físico y el éxito en el tratamiento de enfermedades, como es el caso de la enfermedad de Parkinson en el anciano.
Objetivo
El objetivo de esta investigación es analizar la influencia de la práctica del entrenamiento de resistencia en la correlación del equilibrio y el control postural en personas con párkinson.
Método
Revisión sistemática de acuerdo con las recomendaciones de los artículos Preferred Reporting Items for Systematic Reviews And Meta-Analyses (PRISMA), en consulta con las bases de datos PubMed, Scielo, BVS (Lilacs), ScienceDirect y Cochrane, basados en la influencia del entrenamiento de resistencia en el equilibrio y el control postural en ancianos con párkinson, destacando la principal herramienta de evaluación del Movimiento Sociedad de Trastornos, escala unificada de calificación de la enfermedad de Parkinson.
Resultados
Después de realizar búsquedas en las bases de datos seleccionadas y considerar los criterios de inclusión y exclusión de este estudio, se seleccionaron 10 estudios para componer esta revisión y se acumularon un total de 556 participantes. Se observó que la mayoría de las intervenciones (60%) tuvieron una duración de aproximadamente 30-45 min durante 8 a 12 semanas, los instrumentos de medición más utilizados fueron las puntuaciones Balance Evaluation System Test (BESTest), Freezing of Gait Questionnaire (FOG-Q) y Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS).
Conclusión
El ejercicio físico desempeña un papel fundamental en la intervención y prevención de los síntomas de la enfermedad de Parkinson en lo que respecta al equilibrio, la fuerza y la calidad de vida.
... However, our understanding of how exercise improves mobility, balance, motor control, and gait parameters such as speed, rhythmicity, and stride length needs to be expanded (Figure 1). It is now widely acknowledged that exercise benefits mobility not just by improving physiological function, such as muscle strength and balance (Robertson et al., 2002;Liu-Ambrose et al., 2008, 2013, but also through neural mechanisms (e.g., enhanced neuroplasticity, maintenance of white and gray matter integrity and volume in motor brain areas) (Shepherd, 2001;Colcombe et al., 2003Colcombe et al., , 2006Forrester et al., 2008;Quaney et al., 2009;Petzinger et al., 2010Petzinger et al., , 2013Mang et al., 2013;Perrey, 2013;Duchesne et al., 2016;Hirsch et al., 2016;Nepveu et al., 2017;Steib et al., 2018). Nevertheless, studies providing direct evidence are few (Fisher et al., 2008;Skriver et al., 2014;Bolandzadeh et al., 2015;Ostadan et al., 2016;Hsu et al., 2017a,b;Dal Maso et al., 2018;Hübner et al., 2018;Lehmann et al., 2020). ...
Neural mechanisms, such as enhanced neuroplasticity within the motor system, underpin exercise-induced motor improvements. Being a key mediator of motor plasticity, brain-derived neurotrophic factor (BDNF) is likely to play an important role in mediating exercise positive effects on motor function. Difficulties in assessing brain BDNF levels in humans have drawn attention to quantification of blood BDNF and raise the question of whether peripheral BDNF contributes to exercise-related motor improvements. Methodological and non-methodological factors influence measurements of blood BDNF introducing a substantial variability that complicates result interpretation and leads to inconsistencies among studies. Here, we discuss methodology-related issues and approaches emerging from current findings to reduce variability and increase result reproducibility.
... Studies have shown the importance of intensive care and how exercise induces neuroplasticity in PWP's, which causes improvement in both motor and cognitive circuitry. (Hirsch et al., 2016;Petzinger et al., 2013). ...
Background:
Intensive, multi-disciplinary, rehabilitation programs for patients with Parkinson's disease (PWPs) have shown to be effective. However, most programs are based on in-patient service, which is expensive.
Objective:
To demonstrate the feasibility of a multidisciplinary, intensive, outpatient rehabilitation program (MIOR) for moderate to advanced Parkinson's Disease (H&Y≥2).
Method:
The MIOR program takes place at a community rehabilitation center ('Ezra Le'Marpe'), 3 times a week, 5 hours, 8 weeks, and includes 20 PWPs in each cycle. The multi-disciplinary team includes physical, occupational, speech and hydro therapists. Additional activities include, social work groups, boxing, dancing and bridge.
Results:
Data was collected retroactively for the first two years. Data analysis includes 158 patient files who completed the program (mean disease duration 10.1±6 and mean H&Y stage 2.8±0.67). Assessments were performed at the beginning and end of the intervention. Positive results were collected: improvement in number of falls (p < 0.0001), Functional Independence Measure (p < 0.0001), quality of life (p < 0.01), balance (p < 0.0001), upper limb function (p < 0.0001) and paragraph reading vocal intensity (p < 0.01).
Conclusions:
MIOR is a feasible program, showing positive results in moderate to advanced PWP's, improving quality of life, daily function, and motor performance. The current outcomes demonstrate feasibility of MIOR in addition to medical treatment.
... For example, brain neurotrophic factors can induce neuronal protection and repair mechanisms in the dopaminergic system, which, in turn, increases angiogenesis and functional compensation mechanisms via glutamatergic and serotonergic circuits [26][27][28] . In PD patients, it has been shown that an exercise-induced increase of neurotrophic factors is associated with increased gray matter volume and symptomatic changes 16,27,29 . ...
The lack of physical exercise during the COVID-19 pandemic-related quarantine measures is challenging, especially for patients with Parkinson’s disease (PD). Without regular exercise not only patients, but also nursing staff and physicians soon noticed a deterioration of motor and non-motor symptoms. Reduced functional mobility, increased falls, increased frailty, and decreased quality of life were identified as consequences of increased sedentary behavior. This work overviews the current literature on problems of supplying conventional physiotherapy and the potential of telerehabilitation, allied health services, and patient-initiated exercise for PD patients during the COVID-19 period. We discuss recent studies on approaches that can improve remote provision of exercise to patients, including telerehabilitation, motivational tools, apps, exergaming, and virtual reality (VR) exercise. Additionally, we provide a case report about a 69-year-old PD patient who took part in a 12-week guided climbing course for PD patients prior to the pandemic and found a solution to continue her climbing training independently with an outdoor rope ladder. This case can serve as a best practice example for non-instructed, creative, and patient-initiated exercise in the domestic environment in difficult times, as are the current. Overall, many recent studies on telemedicine, telerehabilitation, and patient-initiated exercises have been published, giving rise to optimism that facilitating remote exercise can help PD patients maintain physical mobility and emotional well-being, even in phases such as the COVID-19 pandemic. The pandemic itself may even boost the need to establish comprehensive and easy-to-do telerehabilitation programs.
... Brain alterations associated with motor deficits include reduced gray matter volume and thickness in the prefrontal, parietal, and motor cortices (Good et al., 2001;Jernigan et al., 2001;Resnick et al., 2003;Salat et al., 2004;Kennedy and Raz, 2005;Rosano et al., 2007a), decreased white matter integrity, particularly of the prefronto-subcortical bundles and corpus callosum (Sullivan et al., 2002;Ota et al., 2006;Zahr et al., 2009;Srikanth et al., 2010;Van Impe et al., 2012;BC et al., 2019), and lower dopaminergic neurotransmission due to a decline in dopamine levels and in the availability of its receptors and transporters (Carlsson and Winblad, 1976;Suhara et al., 1991;Rinne et al., 1993;Volkow et al., 1996Volkow et al., , 1998Wang et al., 1998;Kaasinen et al., 2000Kaasinen et al., , 2002Inoue et al., 2001;Cham et al., 2007Cham et al., , 2008Bohnen et al., 2009;Ishibashi et al., 2009). Exercise can delay and ameliorate age-and disease-induced brain changes by reducing the progression of white matter lesions and decline of gray and white matter volume, and by stimulating neuroplasticity which, in turn, promotes motor learning or re-learning during rehabilitation (Vaynman and Gomez-Pinilla, 2005;Colcombe et al., 2006;Forrester et al., 2008;Quaney et al., 2009;Petzinger et al., 2010Petzinger et al., , 2013Ruscheweyh et al., 2011;Erickson et al., 2011;Mang et al., 2013;Bolandzadeh et al., 2015;Hirsch et al., 2016;Nepveu et al., 2017;Steib et al., 2018) (Fig. 1). ...
Exercise is a promising, cost-effective intervention to augment successful aging and neurorehabilitation. Decline of gray and white matter accompanies physiological aging and contributes to motor deficits in older adults. Exercise is believed to reduce atrophy within the motor system and induce neuroplasticity which in turn helps preserve motor function during aging and promote re-learning of motor skills, for example after stroke. To fully exploit the benefits of exercise, it is crucial to gain a greater understanding of the neurophysiological and molecular mechanisms underlying exercise-induced brain changes that prime neuroplasticity and thus contribute to postponing, slowing and ameliorating age- and disease-related impairments in motor function. This knowledge will allow us to develop more effective, personalized exercise protocols that meet individual needs, thereby increasing the utility of exercise strategies in clinical and non-clinical settings. Here, we review findings from studies that investigated neurophysiological and molecular changes associated with acute or long-term exercise in healthy, young adults and in healthy, postmenopausal women.
... Excitingly, in recent years, clinical studies have demonstrated that treatment with antiparkinsonian drugs may increase BDNF levels [50]. Similarly, exercise therapy can trigger several plasticity-related events in the human PD brain, including corticomotor excitation and changes in BDNF levels [51]. In general, BDNF may be a potential biomarker for evaluating cognitive changes in PD and other neurological syndromes associated with cognitive decline [47]. ...
As the global population ages, the incidence of neurodegenerative diseases has risen. Furthermore, it has been suggested that depression, especially in elderly people, may also be an indication of latent neurodegeneration. Stroke, Alzheimer’s disease (AD), and Parkinson’s disease (PD) are usually accompanied by depression. The urgent challenge is further enforced by psychiatric comorbid conditions, particularly the feeling of despair in these patients. Fortunately, as our understanding of the neurobiological substrates of maladies affecting the central nervous system (CNS) has increased, more therapeutic options and novel potential biological mechanisms have been presented: (1) Neurodegenerative diseases share some similarities in their pathological characteristics, including changes in neuron structure or function and neuronal plasticity. (2) MicroRNAs (miRNAs) are small noncoding RNAs that contribute to the pathogenesis of diverse neurological disease. (3) One ubiquitous neurotrophin, brain-derived neurotrophic factor (BDNF), is crucial for the development of the nervous system. Accumulating data have indicated that miRNAs not only are related to BDNF regulation but also can directly bind with the 3 ′ -UTR of BDNF to regulate BDNF and participate in neuroplasticity. In this short review, we present evidence of shared biological substrates among stroke, AD, PD, and depression and summarize the possible influencing mechanisms of acupuncture on the neuroplasticity of these diseases. We discuss neuroplasticity underscored by the roles of miRNAs and BDNF, which might further reveal the potential biological mechanism of neurodegenerative diseases and depression by acupuncture.
... Further, using these techniques in conjunction with yoga likely amplifies these gains, as exercise has now been shown to increase the density of striatal dopamine receptors (Fisher et al., 2013), expand grey matter volume within the basal ganglia and other cortical structures (Sehm et al., 2014), and enhance the release of neurotrophic factors within humans (Frazzitta et al., 2014). Acknowledging that research concerning exercise-induced neuroplasticity in Parkinson's patients is still in its infancy (for reviews see Hirsch et al., 2016;Johansson et al., 2020;Petzinger et al., 2013), accumulating evidence, including data offered by the current study, suggest that combined psychophysical programs can offer a neuroprotective effect in PD patients. Future research should continue to examine the effectiveness of such programs by testing patients in both the "ON" and "OFF" medication state to better parse distinct therapeutic advantages of pharmacology and exercise. ...
This study compared the effectiveness of two proprioceptive exercise programs for persons diagnosed with Parkinson’s disease (PD). Thirty-three patients with mild to moderate PD were randomly assigned to a yoga meditation program (YoMed) or to an established proprioceptive training program (PRO). Both interventions included twice weekly sessions (45 minutes each), spanning a 12-week period. Outcome measures included: joint position sense (JPS 45 °, JPS 55 °, JPS 65 °) and joint kinesthesia (JK Flex and JK Ext ), the Tinetti Balance Assessment Tool (TIN), Falls Efficacy Scale (FES), Balance Error Scoring System (BESS), dynamic posturography (DMA and TIME) and the Timed Up-and-Go Test (TUG). Test administrators were blinded to group affiliation. Significant between-group differences favoring the YoMed group were observed for TIN ( p = 0.01, d = 0.77) and JK Flex ( p = 0.05, d = −0.72). DMA and TIME scores significantly improved for both groups, and no adverse events were reported. These findings indicate that the YoMed program is safe and effective for patients with PD. Researchers should continue to examine the clinical efficacy of mind-body techniques to improve movement control and body awareness in this population.
... In addition, several meta-analyses and systematic reviews have concluded that exercise and physical therapy improve many Parkinson disease-specific motor and nonmotor symptoms [2][3][4][5][6]. Importantly, there are several lines of evidence, using rodent Parkinson disease models and in humans with Parkinson disease, that suggest a possible disease-modifying effect of exercise on Parkinson disease [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. ...
Background
Many people with Parkinson disease do not have access to exercise programs that are specifically tailored to their needs and capabilities. This mobile app allows people with Parkinson disease to access Parkinson disease–specific exercises that are individually tailored using in-app demographic questions and performance tests which are fed into an algorithm which in turn produces a video-guided exercise program.
Objective
To test the feasibility, safety, and signal of efficacy of a mobile app that facilitates exercise for people with Parkinson disease.
MethodsA prospective, single-cohort design of people with Parkinson disease who had downloaded the 9zest app for exercise was used for this 12-week pilot study. Participants, who were recruited online, were encouraged to exercise with the full automated app for ≥150 minutes each week. The primary endpoints were feasibility (app usage and usability questions) and safety (adverse events and falls). The primary endpoints for signal of efficacy were a comparison of the in-app baseline and 8-week outcomes on the 30-second Sit-To-Stand (STS) test, Timed Up and Go (TUG) test, and the Parkinson’s Disease Questionnaire 8 (PDQ8).
ResultsFor feasibility, of the 28 participants that completed the study, 12 participants averaged >150 minutes of app usage per week (3 averaged 120-150, 4 averaged 90-120, and 9 averaged less than 90 minutes). A majority of participants (>74%) felt the exercise was of value (16/19; 9 nonrespondents), provided adequate instruction (14/19; 9 nonrespondents), and was appropriate for level of function (16/19; 9 nonrespondents). For safety, there were no serious adverse events that occurred during the app-guided exercise. There were 4 reports of strain/sprain injuries while using the app among 3 participants, none of which necessitated medical attention. For signal of efficacy, there was improvement for each of the primary endpoints: STS (P=.01), TUG (P
... Also, our findings suggest that a combination of modifiable environment and lifestyle factors contribute to their differential expression. Prior epidemiological studies have confirmed the beneficial effects of regular physical exercise [31,32], although we cannot exclude that those in the mPD group reported lower physical activity at baseline due to their older age at PD onset or other selection biases. On the other end, detrimental effects associated with exposure to pesticide are well documented [33,34], although ours stand in contrast with a reported association with tremordominant PD [35]. ...
Objective
We sought to evaluate demographic, clinical, and habits/occupational variables between phenotypic extremes in Parkinson’s disease (PD).Methods
Databases from nine movement disorders centers across seven countries were retrospectively searched for subjects meeting criteria for very slowly progressive, benign, PD (bPD) and rapidly progressive, malignant, PD (mPD). bPD was defined as Hoehn and Yahr (H&Y) stage ≤ 3, normal cognitive function, and Schwab and England (S&E) score ≥ 70 after ≥ 20 years of PD (≥ 10 years if older than 60 at PD onset); mPD as H&Y > 3, S&E score < 70, and cognitive impairment within 10 years from PD onset. We performed between-group analysis of demographic, habits/occupational, and clinical features at baseline and follow-up and unsupervised data-driven analysis of the clinical homogeneity of bPD and mPD.ResultsAt onset, bPD subjects (n = 210) were younger, had a single limb affected, lower severity and greater asymmetry of symptoms, and lower prevalence of depression than mPD (n = 155). bPD was associated with active smoking and physical activity, mPD with agricultural occupation. At follow-up, mPD showed higher prevalence of depression, hallucinations, dysautonomia, and REM behaviour disorder. Interestingly, the odds of mPD were significantly reduced by the presence of dyskinesia and wearing-off. Data-driven analysis confirmed the independent clustering of bPD and mPD, with age at onset emerging as a critical discriminant between the two groups (< 46-year-old vs. > 68-year-old).Conclusions
Phenotypic PD extremes showed distinct demographic, clinical, and habits/occupational factors. Motor complications may be conceived as markers of therapeutic success given their attenuating effects on the odds of mPD.
... Exercise improves the health of the brain, including increased expression of neurotrophic factors, greater blood flow, altered immune response, increased neurogenesis, and altered metabolism [44]. Such changes may enhance the neuronal circuitry between the basal ganglia and its cortical and thalamic connections, ultimately improving motor, nonmotor, and cognitive behavior in patients with PD [45]. ...
Parkinson disease (PD) is a chronic neurodegenerative condition that leads to progressive disability. PD-related reductions in muscle strength have been reported to be associated with lower functional performance and balance confidence with an increased risk of falls. Progressive resistance training (PRT) improves strength, balance, and functional abilities. This umbrella review examines the efficacy of PRT regarding muscular strength in PD patients. The PubMed, PEDro, Scopus, and Cochrane Library databases were searched from January 2009 to August 2019 for systematic reviews and meta-analyses conducted in English. The populations included had diagnoses of PD and consisted of males and females aged >18 years old. Outcomes measured were muscle strength and enhanced physical function. Eight papers (six systematic reviews and meta-analyses and two systematic reviews) were considered relevant for qualitative analysis. In six of the eight studies, the reported severity of PD was mild to moderate. Each study analyzed how PRT elicited positive effects on muscle strength in PD patients, suggesting 10 weeks on average of progressive resistance exercises for the upper and lower limbs two to three times per week. However, none of the studies considered the postworkout follow-up, and there was no detailed evidence about the value of PRT in preventing falls. The possibility of PRT exercises being effective for increasing muscle strength in patients with PD, but without comorbidities or severe disability, is discussed. Overall, this review suggests that PRT should be included in rehabilitation programs for PD patients, in combination with balance training for postural control and other types of exercise, in order to preserve cardiorespiratory fitness and improve endurance in daily life activities.
... It applies, therefore, to any work that necessarily involves a movement of the body. Due to the characteristics of the patients, the selected motor task was pedaling, which consisted of indoor cycling [37,38] for a period of 60 seconds and undertaken in the sitting position. e patient, seated in a chair with armrests, adjusts the pedals and performs a small warm-up before starting the test. ...
Introduction. Cognitive decline usually coexists with motor impairment in PD. Multitask settings provide appropriate measures to evaluate the complex interaction between motor and cognitive impairments. The main objective was to analyze which concurrent task, i. e., motor or hybrid motor-cognitive, in combination with a cognitive task better differentiates between PD patients with mild and moderate levels of disease. Methods. Thirty-seven individuals (19 male and 18 female) with idiopathic PD performed dual and triple tasks combining a cognitive task (phonemic fluency) with motor (pedaling) and/or cognitive-motor hybrid (tracking) tasks. Mild and moderate disability PD groups were specified considering the Hoehn and Yahr scale. Mixed ANOVA analyses for each of the concurrent task were carried out to test differences between the single and dual or triple condition performances comparing the low and high PD disability groups. Supplementary mixed ANCOVA analysis was performed considering the cognitive status as the covariate. Results. The only significant differences between disability PD groups were found for performances in the cognitive-motor hybrid (tracking) task, both in dual and triple conditions. Our results showed a better performance for the mild rather than for the moderate disability group in the single condition task and a significant decline of the mild disability group in the dual and triple condition when compared to the levels of those shown by the moderate disability group. The group-condition interaction remained significant when the cognitive status was statistically controlled. Conclusion. The hybrid of motor-cognitive task combining with a cognitive task (i. e., fluency) successfully differentiated between mild and moderate PD patients in the context of dual and triple multitask sets even when the cognitive status was statistically controlled. Our results highlight the importance of jointly measuring the complex interplay between motor and cognitive skills in PD.
1. Introduction
Parkinson’s disease (PD) is mainly characterized by the progressive impairment of motor abilities [1]. However, cognitive decline usually coexists with motor impairment as a consequence of the neurodegenerative progression [2]. Despite the relationship between cognitive and motor impairments in PD [3], cognitive performance is usually measured regardless of the motor impairment or as with other nonmotor features of the illness, does not receive adequate attention [4].
The interaction between the motor and cognitive components seems to determine the functional capacity and should be considered simultaneously in the evaluation of the progression of PD [5]. Thus, voluntary movements in everyday life rarely are wholly automatic and therefore impose cognitive demands that could impair cognitive performance [6]. Conversely, because of loss of movement automaticity in PD, higher demands in attentional resources seem to be expected to maintain movement amplitude, rhythm, or posture [7, 8]. As some attentional resources must be allocated to the voluntary movement, performing a concurrent cognitive task may well interfere in the motor performance of PD patients [9].
The concurrent-task paradigm (multitask setting) constitutes an appropriate paradigm to evaluate the reciprocal influences between the motor and cognitive components because reciprocal costs can easily be estimated considering how the performance in both motor and cognitive tasks is hindered in concurrent condition regarding its performances in the single condition. The analysis of the relationships between cognitive and motor impairments in PD should be useful to assess the progression of symptoms, optimize the effectiveness of interventions, and finally, improve the patient’s quality of life [10]. The concurrent-task paradigm provides a way of measuring the ability to share attentional resources in order to attend to the requirements of the two or more concurrent tasks (e.g., usually two, “dual,” or at most, three concurrent tasks, “triple”) devoted to the measurement of either cognitive, motoric, or both skills [11]. Since PD leads to a loss of automaticity in motor actions that compete for the available attentional resources, execution in the dual condition is expected to decline, particularly when the concurrent tasks impose high motor and cognitive demands. Despite the subsidiary motor and cognitive processes that are generally involved in most experimental tasks (e.g., perceptual processes and motor responses), the most demanding cognitive or motor component of a task corresponds to those that rely on voluntary processes, more resource-consuming, and those that can be considered core processes to achieve the main task-goal.
As far as we know, no study has been conducted to analyze the influence of the triple condition in patients with PD, but considering what has been reported for healthy older adults [12], a decline in performance compared to that observed in the dual condition could be expected also in PD patients.
Some studies carried out on healthy older adults have pointed out that the multitasking costs (i. e., performance worseness in the concurrent condition compared to the single condition) were higher in motor-cognitive than in motor-motor task sets [13–15]. Evidence from research in PD patients is not conclusive. Thus, although some studies found increased dual costs in motor-cognitive dual task sets [14, 16], some evidence pointed out similar dual task costs for motor-motor and motor-cognitive dual task sets [17]. Even when higher dual costs are associated with motor-cognitive dual task sets, it is not clear which of the concurrent tasks, cognitive or motor, might lead higher dual costs. In addition, the specific effects that a more hybrid motor-cognitive concurrent task could impose on the cognitive load when it is performed in a multitask setting should also be considered. Measurement of dual costs should be made carefully in order to prevent confounding the dual effect with differential demands associated to the disability level [18–20] or interference between processing mechanisms involved in both concurrent tasks [21]. Thus, multitask costs could be artificially increased when concurrent tasks involve similar processes for the input processing (e. g., visual and auditory), the selection of responses or the stimulus-response mapping according to the task response-criteria. In these conditions, the organization of the mental-set will be more difficult, and concurrent performance will be more prone to error and slowness [21].
Our aim was to elucidate which concurrent task (i. e., motor or hybrid motor-cognitive) in combination with a cognitive task is better to differentiate between PD patients with mild and moderate levels of disease [22]. Three tasks, namely, phonemic fluency (cognitive), pedaling (motor), and tracking (hybrid), were performed in single, dual (fluency-pedaling; fluency-tracking), and triple (fluency-pedaling-tracking) conditions. Single, dual, and triple performances were compared between mild and moderate disability PD groups, with cognitive status statistically controlled for. Among the concurrent cognitive tasks used in PD patients, verbal fluency tasks have been extensively studied [23, 24]. Unlike action fluency [25–28], phonemic fluency seems to be relatively unimpaired in PD [23, 24]. Regarding motor tasks, automated motor activities such as cycling or pedaling are good candidates for concurrent tasks since they provide purer motor measures and prevent cognitive interference in motor performance. Results have shown that these tasks seem to be largely preserved in PD patients [29, 30], and even improvements in dual costs have been reported for several cognitive measures in patients with PD [31, 32] and other motor concurrent tasks in healthy older adults [11], when this concurrent task is implemented in dual paradigms. The tracking test is a simple task that requires visuospatial and fine motor skills to quickly cross a series of circles arranged sequentially. This task was developed specifically to reliably measure dual-tasking ability in clinical practice [33] and unlikely to interfere with the main cognitive (i. e., lexical access) and motor (i. e., automated lower limb movement) processing mechanisms, respectively, involved in fluency and in pedaling.
In light of dual task taxonomy by McIsaac et al. [11], higher dual costs are expected for concurrent tasks showing higher complexity and novelty. Therefore, fluency-tracking should be more likely to show dual costs than fluency-pedaling and also be more likely to be observed in the Fluency and Tracking concurrent tasks because more complexity and novelty are implicit here than in the pedaling task. A higher cost should be expected in triple rather than in dual conditions because of the difficulty to increase and also in the advanced rather than in the early stages of PD. Group differences and dual or triple costs should be reduced or removed for the cognitive concurrent task and even for the hybrid cognitive-motor task when general cognitive status is statically controlled.
2. Methodology
2.1. Participants
Thirty-seven individuals (19 male and 18 female) with idiopathic PD were recruited for this baseline analysis. All patients with PD had been clinically diagnosed with idiopathic PD by a neurologist and were tested in the practical ON levodopa state, after ingesting antiparkinsonian medication (they reported that levodopa had taken its full effect). Subjects were recruited from Parkinson associations. They were invited to participate if they were between the ages of 50 and 85 years, were on levodopa treatment, experienced motor response fluctuations, and were able to ambulate independently. Five patients were excluded because they did not complete all the tasks.
Participants were classified as mild disability (stages I and II of the disease) and moderate disability (stages III and IV) according to the Hoehn and Yahr scale [22]. This scale is used internationally for the global assessment of PD and was designed to measure impairments associated with the disease progression. None of the participants presented severe disability (stage V).
All patients gave their written informed consent to participate in this study according to the Declaration of Helsinki. The protocol of this study was approved by the Research Ethics Committee of the Faculty of Education and Sport Sciences and then assigned code number 12-2205-17.
2.2. Assessment
2.2.1. Gait
This variable was assessed using the Walk protocol with Wiva® sensors [34], a set of wireless inertial detection devices placed in the L4-L5 spinal segment. Wiva® sensors include an accelerometer, a magnetometer, and a gyroscope that allow professionals and practitioners to gather information about spatiotemporal parameters of the gait achieved during the Walk protocol. The Walk protocol consists of the patient moving in a straight line along a corridor of 80 cm for a distance of 10 m at a constant speed. This protocol is repeated twice, and the average of the obtained data is recorded. Variables recorded are stride speed (m/s), cadence (strides/min), stride length (m), simple support duration (s), double support duration (s), and gait cycle duration (s). All thes information was saved and sent to a PC via Bluetooth with Biomech Study 2011 v.1.1.
2.2.2. Cognitive Status
The cognitive status of the participants was measured with the Montreal Cognitive Assessment (MoCA) [35]. The MoCA test is a widely used tool comprising 22 items and employed to screen patients with suspected mild cognitive impairment. The total score for the MoCA ranges from 0 to 30 points. It includes items from the following cognitive domains: memory, naming, language, visuospatial/executive functions, abstraction, attention/concentration/calculation, and orientation. In this study, we used Spanish normative scores for age and educational level [36].
2.2.3. Motor Task
Tasks that mainly involve a mechanical or repetitive physical movement by the patient are representative of pure motor tasks. It applies, therefore, to any work that necessarily involves a movement of the body. Due to the characteristics of the patients, the selected motor task was pedaling, which consisted of indoor cycling [37, 38] for a period of 60 seconds and undertaken in the sitting position. The patient, seated in a chair with armrests, adjusts the pedals and performs a small warm-up before starting the test. The test consists of a series of cycles (without resistance) back and forth to become familiar with indoor cycling. Then, the cycle counter is set to “0” and the participant is told that he/she must pedal continuously for 60 seconds at a constant pace and at a cadence that allows the subject to speak at the same time that he/she is pedaling.
2.2.4. Cognitive Task
The cognitive task chosen for the development of the study was a phonemic verbal fluency task. Verbal fluency tasks are often included in neuropsychological assessment to indicate cognitive impairment in persons with neurodegenerative diseases such as PD [39]. The task undertaken in this study was a task of phonemic fluency, in which each patient had to say as many words as possible over 60 seconds, having to start them by the assigned letters P, R, or M, having indicated previously that no proper names or words derived from others were valid (verbal conjugations and words from the same family). The frequency of Spanish words that begin with the letters P, R, and M is similar. To avoid the learning effect, each letter was used only in one of the experimental conditions.
2.2.5. Motor-Cognitive Task
The task administered consists of using a pencil to draw a line through circles arranged in a path around a sheet of A3 paper containing 319 circles [33]. After a practice trial, the participants have 60 seconds to go through the circles along the path without lifting the pencil. The number of circles crossed with the pencil within the 60 seconds is calculated.
2.2.6. Dual and Triple Tasks
The same measures were recorded in the phonemic fluency (number of correct words), tracking (number of circles crossed) and pedaling (number of pedal strokes) in the simple, dual and triple conditions. The phonemic fluency was measured by the number of correct words starting with the designated letter produced in 60 seconds. In the tracking task, the number of circles crossed with the pencil within the 60 seconds was recorded. In the pedaling task, the number of pedal strokes was recorded after the 60 seconds.
2.2.7. Procedure
The tasks were performed by each patient individually, in a spacious and comfortable location and always supervised by the evaluators. The patients sat in a chair without armrests with a height of 47 cm and with the backrest fixed to the wall. In front of the patients was a desk 72 cm high. Tasks were administered to the participants seven days a week and always in the morning. The protocol was carried out within two weeks, and all measurements for each patient were taken on the same day.
All the tasks and conditions were applicable to the sample participants [40]. Tasks were performed first in the single condition and in the following order: (1) phonemic fluency, (2) tracking, and (3) pedaling. Subsequently, the tasks were performed in the dual mode in a counterbalanced manner, combining them as follows: phonemic fluency + tracking and phonemic fluency + pedaling or phonemic fluency + pedaling and phonemic fluency + tracking. Finally, for the triple-task condition, participants were asked to perform the phonemic fluency, the tracking, and the pedaling tasks simultaneously. In these dual and triple conditions, participants were asked to perform the phonemic fluency jointly with the another concurrent task (either with tracking or with pedaling task) for 60 s.
2.2.8. Statistical Analysis
A descriptive analysis was carried out through measurements of central tendency (mean) and dispersion (standard deviation) to describe the sample, thus stratifying the description according to the stage in which the sample is located. Student’s t-tests were conducted by comparing mild and moderate disability groups for age (years), years of education, MoCA score, and gait: spatiotemporal parameters, phonemic fluency (simple, dual with tracking, dual with pedaling, and triple), tracking (simple, dual, and triple), and pedaling (simple, dual, and triple). Mixed ANOVA analyses were performed to test group differences (mild and moderate disability) between single and dual conditions for phonemic fluency, tracking, and pedaling tasks in the following combinations: phonemic fluency-tracking and phonemic fluency-pedaling, considering the MoCA total score as the covariate. Similarly, mixed ANOVA analyses were also performed to test group differences between single and triple conditions for each of the following tasks: phonemic fluency, tracking, and pedaling, also controlling for MoCA total score. The estimated marginal means represented in the figures correspond to the average scores for each level of combination of the factors considered (i.e., disability and condition), adjusted for the covariate of the cognitive status. Multiple-comparison post hoc Bonferroni correction was used to evaluate pairwise significant comparisons. The alpha value was established at .05 for all analyses, and the partial eta squared value is reported as an estimate of effect size in the mixed ANCOVAs.
3. Results
3.1. Group Comparisons
Comparisons between groups with mild and moderate disability are shown in Table 1. Although, in general, performances were better in the mild disability group, significant differences were only reached in stride speed, tracking in the single condition, and pedaling in both the single and the triple conditions.
Mild disability
Moderate disability
t
Age (years)
69.42 (10.64)
71.00 (7.38)
−0.46
Years of education
9.36 (2.43)
11.15 (4.24)
−1.51
MoCA score
18.90 (7.53)
17.23 (8.52)
0.58
Gait (spatiotemporal parameters)
Stride speed (m/s)
0.83 (0.28)
0.63 (0.22)
2.19
Cadence (strides/min)
91.56 (11.27)
78.34 (14.71)
1.44
Stride length (m)
1.09 (0.23)
1.04 (0.22)
0.61
Simple support duration (s)
0.75 (0.09)
0.71 (0.08)
0.18
Double support duration (s)
0.23 (0.08)
0.24 (0.07)
−0.87
Gait cycle duration (s)
1.26 (0.16)
1.49 (0.42)
−0.90
Phonemic fluency
Single
6.89 (4.20)
5.77 (4.71)
0.71
Dual (with tracking)
5.26 (4.23)
3.69 (3.59)
1.10
Dual (with pedaling)
7.21 (5.01)
5.46 (4.20)
1.03
Triple
5.42 (3.66)
3.41 (3.68)
1.48
Tracking
Single
53.05 (29.77)
27.23 (17.32)
2.81
Dual
35.74 (26.46)
27.69 (18.93)
0.94
Triple
32.42 (24.33)
25.17 (20.29)
0.86
Pedaling
Single
71.95 (24.86)
48.62 (20.65)
2.79
Dual
51.05 (16.70)
39.08 (19.34)
1.87
Triple
38.10 (17.97)
16.75 (14.67)
3.45
; .
... PD is one of the most common progressive neurodegenerative disorders, leading to loss of motor function and decreased quality of life. A study showed that exercise can trigger several plasticity-related events in the brain of PD patients, including cortical motor excitement, increasing and decreasing gray matter volume, and altering BDNF levels [2]. Increasing evidence supports the role of exercise in improving both motor and non-motor outcomes in PD [3], [4]. ...
A kind of wearable exoskeleton soft rehabilitation glove is proposed for the dementia in Parkinson's disease (PD) patients with loss of hand function, limited range of motion, and insufficient finger muscle strength to carry out rehabilitation exercise training in a passive or auxiliary way. A novel soft joint structure based on composite fabric material is introduced for the design of the soft glove with bionic method, and experiments are conducted to verify the effeteness of the proposed soft rehabilitation glove. The test results showed that when the fluid pressure was 0.42 MPa, the joint angle of MCP, PIP and DIP could be up to 81 °, 98 °, 72 °, and produce output torque of 1.18Nm, 1.44Nm and 1.82Nm respectively, which meets the requirements of the hand rehabilitation. A dynamic rehabilitation-training test of the rehabilitation glove was also carried out, and the results showed that the movement frequency of soft fingers could reach 30 times/min, which is sufficient for repetitive flexion/extension exercise. In order to verify the grasping characteristics of the soft glove for irregular objects, experiments were carried out. The experimental results showed that the bionic soft glove was dexterous in grasping, which conforms to the universal grasping characteristics of human hands, has the function of assisting daily life (ADL), and meets the requirements of rehabilitation.
Pharmacological treatments in Parkinson’s disease (PD), albeit effective in alleviating many motor symptoms, have limited effects in non-motor signatures as cognitive impairment, as well as in other aspects included postural instability. Consequently, complementary interventions are nowadays a prerogative of clinical practice managing PD symptomatology. In this pilot longitudinal study, we recruited twenty-four PD patients participating in one of two interventions: adapted Argentine Tango or group-based physiotherapy. Participants underwent a motor and neuropsychological evaluation before and after four months of activities, carried out twice a week. We found a general stabilization of motor and cognitive abilities, with significant improvements in several motor skills, mainly pertaining to static and dynamic balance, similarly in both groups. At cognitive level, we measured a significant improvement in both groups in the Action Naming task. Interestingly, only PD patients in the Tango group improved their performance in the test measuring facial emotion recognition. These findings highlight the crucial role that physical activities have in the stabilization and slowdown of disease’s progression in PD. They further highlight the beneficial effects of a group-based physical intervention, which, especially in the case of Tango, could lead to behavioral ameliorations in domains other than the motor, such as emotion recognition.
The inpatient Parkinson’s disease multimodal complex treatment (PD-MCT) was applied more than 15,000 times in 2022, in Germany. This number is increasing as is Parkinson’s disease (PD), which affects more than 400,000 people in Germany and leads to 100,000 disability-adjusted life years. In recent years, several observational studies have been conducted on the effectiveness of this kind of multidisciplinary care.
To summarize and discuss the evidence on the nature, benefits and potential of PD-MCT.
A narrative review of selected empirical findings was carried out.
The PD-MCT frequently lasts for 2–3 weeks and aims to maintain the quality of life of people with PD. Disease symptoms and activities of daily living are jointly improved by pharmacological strategies and activating therapies (physiotherapy, occupational therapy, speech and language therapy, physical training, art therapy). The PD-MCT is a useful measure to avoid or mitigate crisis situations in the course of the disease. A total of eight observational studies (n = 1246) have shown good effectiveness with a total mean improvement of the International Parkinson and Movement Disorder Society unified Parkinson’s disease rating scale III (MDS-UPDRS III) by 7.8 points. The transfer of effects into everyday life through intensive and specialized community-based care must be ensured in order to achieve sustained effects on the quality of life. Ideally, this transfer can be supported by integrated PD networks and digital technologies in the future.
There is potential for development in the standardization, patient selection and quality assurance of PD-MCT as well as in the embedding in care structures such as PD networks. Open research questions include a precise definition of the target group and higher quality evidence of short-term and long-term effectiveness.
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.
Introduction:
Exercise therapy may increase brain-derived neurotrophic factor (BDNF) levels and improve clinical outcomes in people living with Parkinson's disease (PD). This systematic review was performed to investigate the effect of exercise therapy on BDNF levels and clinical outcomes in human PD and to discuss mechanisms proposed by authors.
Method:
A search on the literature was performed on PubMed up to December 2023 using the following key words: Parkinson's disease AND exercise, exercise therapy, neurological rehabilitation AND brain-derived neurotrophic factor, brain-derived neurotrophic factor/blood, brain-derived neurotrophic factor/cerebrospinal fluid AND randomized clinical trial, intervention study. Only randomized clinical trials comparing an exercise intervention to treatment as usual, usual care (UC), sham intervention, or no intervention were included.
Results:
A meta-analysis of BDNF outcomes with pooled data from five trials (N = 216 participants) resulted in a significant standardized mean difference (SMD) of 1.20 [95% CI 0.53 to 1.87; Z = 3.52, p = 0.0004, I2 = 77%], favoring exercise using motorized treadmill, Speedflex machine, rowing machine, and non-specified exercise. Significant improvements were found in Unified Parkinson's Disease Rating Scale (UPDRS), UPDRS-III, 6 Minute Walk Test (6MWT), and Berg Balance Scale (BBS). Methodological quality of trials was categorized as "good" in three trials, "fair" in one trial, and "poor" in one trial.
Conclusion:
Key results of this systematic review are that exercise therapy is effective in raising serum BDNF levels and seems effective in alleviating PD motor symptoms. Exercise therapy confers neuroplastic effects on Parkinson brain, mediated, in part, by BDNF.
Background
‘PD Warrior’ (PDW) is a popular exercise program for Parkinson's disease; however, there are no published studies on the outcomes of the program.
Aims
To investigate short‐term functional and quality of life (QoL) outcomes after the PDW 10‐week program in a pilot study of individuals with early Parkinson's Disease (PD).
Methods
Twenty individuals with PD (Hoehn & Yahr 1–3) attending a hospital outpatient clinic were recruited into the PDW 10‐week program, comprising a weekly 1‐h supervised class complemented by an individualised daily home exercise program. Participants had the following assessments at baseline and after completion of the program: Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) Part III, timed up‐and‐go (TUG), 10‐m walk test (10mWT), 6‐min walking test (6MWT), balance tests, fine motor skills, 7‐day Parkinson's KinetiGraph (PKG) and PDQ‐39 QoL scale.
Results
Seventeen individuals completed the program. Significant improvements were observed in MDS‐UPDRS motor score ( P = 0.019, d = 0.68, MCID 7); 6MWT distance ( P < 0.001, d = 1.16); walking time during motor or cognitive dual tasking ( P = 0.006, d = 0.77; P = 0.005, d = 0.79, respectively); and the PDQ‐39 emotional well‐being subdomain ( P = 0.009; MCID 4.2); as well as improvements trending to significance in bradykinesia ( P = 0.025, d = 0.73), 10mWT walking time ( P = 0.023, d = 0.61) and borderline improvement in balance ( P = 0.056, d = 0.50).
Conclusions
The outcomes of this study support the efficacy of the PDW program in individuals with early PD and provide justification for future trials and investigation of its effects.
Purpose:
The study aims to assess the efficacy of robot-assisted rehabilitation training on upper and lower limb motor function and fatigue in Parkinson's disease (PD), and to explore the best-acting robotic rehabilitation program.
Methods:
We searched studies in seven databases and the search period was from the build to 30 June 2023. Two researchers independently screened studies and assessed the quality of the studies for data extraction.
Results:
A total of 21 studies were included, 18 studies related to lower limbs rehabilitation and 3 studies related to upper limbs rehabilitation, involving a total of 787 participants. The results showed that robot-assisted rehabilitation significantly improved indicators of lower limb motor function UPDRS Part III (WMD = -3.58, 95% CI = -5.91 to -1.25, p = 0.003) and BBS (WMD = 4.24, 95% CI = 2.88 to 5.54, p < 0.001), as well as non-motor symptoms of fatigue (WMD = -13.39, 95% CI = -17.92 to -8.86, p < 0.001) in PD patients. At the level of upper limb function, there was no statistically significant difference in the outcome measures of PFS (WMD = -0.25, 95% CI = -4.44 to 3.93, p = 0.9) and BBT (WMD = 1.73, 95% CI = -2.85 to 6.33, p = 0.458).
Conclusion:
Robot-assisted rehabilitation significantly improved motor function, fatigue, and balance confidence in PD patients, but current evidence doesn't show that intelligent rehabilitation systems improve upper limb function. In particular, robotics combined with virtual reality worked best.
A Doença de Parkinson (DP) é uma doença crônica que atinge cerca de 6,1 milhões de pessoas e que figura em primeiro lugar no ranking das afecções neurodegenerativas que mais crescem em quantidade de portadores no mundo (DORSEY et al, 2018). A DP, que é majoritariamente conhecida por seus sintomas motores, hoje possui um quadro clínico ampliado, com sintomas neuropsiquiátricos, autonômicos e sensoriais. Até o momento, o tratamento da DP é feito majoritariamente com levodopa (L-DOPA), que, no início, é eficaz para os sintomas motores. Entretanto, a terapia não interrompe a progressão da doença e com o tempo pode perder a eficácia, necessitando de ajustes e complementações com outros fármacos e terapias. Assim, o objetivo deste estudo é compilar as terapias para a Doença de Parkinson que atualmente estão sendo pesquisadas por testes clínicos no contexto brasileiro. Para tal, foi realizada uma revisão integrativa da literatura científica, tendo como base artigos disponibilizados nas seguintes plataformas: Scientific Eletronic Library Online – SCIELO, a U.S. National Library of Medicine (NLM) - PubMed e ScienceDirect. Visa-se, por meio disso, reunir informações úteis para o tratamento clínico mais amplo/holístico de pacientes com doença de Parkinson. Os estudos demonstraram o valor da estimulação cerebral profunda (ECP), da L-DOPA para além dos sintomas motores, dos exercícios e do manejo de quedas no tratamento da doença. Mesmo assim, esses resultados são estimulantes para que se continue pesquisando terapias alternativas para a DP.
Background:
Parkinson's disease (PD) is a progressive, neurodegenerative disease with motor symptoms that are well understood, but non-motor symptoms may be present and appear at different temporal stages of the disease. Physical activity based on dance movements is emerging as a complementary therapeutic approach to a range of PD symptoms as a multidimensional activity that requires rhythmic synchronization and more neuromuscular functions.
Objective:
To evaluate the effects of physical activity based on dance movements on the movement, executive functions, depressive symptoms, quality of life, and severity of PD in individuals diagnosed with PD.
Methods:
13 individuals with PD (Hoehn & Yahr I-III, MDS-UPDRS 67.62 ± 20.83), underwent physical activity based on dance movements (2x week for 6 months). Participants were assessed at baseline and after 6 months on movement (POMA, TUG and MDS-UPDRS Part III), executive function (FAB), depressive symptoms (MADRS), quality of life (PDQ-39), and severity of PD (MDS-UPDRS TOTAL). Student's t-test was used to compare pre and post-intervention results.
Results:
We observed a significant improvement in the movement (balance and gait) by the POMA test, p = 0.0207, executive function by the FAB test, p = 0.0074, abstract reasoning and inhibitory control by the FAB, Conceptualization test, p = 0.0062, and Inhibitory Control, p = 0.0064, depressive symptoms assessed by the MADRS test significantly reduced, p = 0.0214, and the quality of life by the PDQ-39 had a significant increase after the intervention, p = 0.0006, showed significant improvements between the pre-and post-intervention periods of physical activity based on dance movements.
Conclusion:
Physical activity based on dance movements contributed to significant improvements in movement (balance and gait), executive functions, especially in cognitive flexibility and inhibitory control, and the quality of life too. Sensorimotor integration, most cognitive processing and social skills may have contributed to the results.
Trial registration:
The study was registered in the Brazilian registry of clinical trials: RBR-3bhbrb5.
Background: Parkinson’s disease (PD) is a neurodegenerative disease in which the progressive loss of dopaminergic neurons (DA) leads to initially sporadic and eventually widespread damage of the nervous system resulting in significant musculoskeletal and cognitive deterioration. Loss of motor function alongside increasing cognitive impairment is part of the natural disease progression. Gait is often considered an automatic activity; however, walking is the result of a delicate balance of multiple systems which maintain the body’s center of mass over an ever-changing base of support. It is a complex motor behavior that requires components of attention and memory to prevent falls and injury. In addition, evidence points to the critical role of salient visual information to gait adaptability. There is a growing understanding that treatment for PD needs to address movement as it occurs naturally and walking needs to be practiced in more complex environments than traditional therapy has provided.
Methods
In this single-blinded randomized-controlled pilot study, an immersive treadmill training was piloted to determine feasibility and preliminary efficacy on gait and cognition in people with PD. Eighteen participants with Hoehn and Yahr stages I-III PD were randomized to either an intervention or a waitlist control group. Following baseline data collection, the intervention group trained for 30 min, three times/week for 4 weeks on a split belt treadmill combined with a first-person immersive video game targeting visuospatial skills and working memory. Assessment was repeated after 4 weeks of training for the experimental group and 1-month after baseline for the control group. Primary motor outcomes were captured with the APDM Opal sensors during 6 MWT, TUG, and TUG Cognitive. Secondary outcomes of cognition were measured with the Montreal Cognitive Assessment (MoCA), Verbal Fluency (Fruit, Vegetable, and Animal) and the Symbol Digit Modality Test (SDMT). Within subject differences were calculated using the Wilcoxon Signed Ranked Test and between subject comparisons were analyzed using the Mann Whitney U -test.
Results
This novel treadmill training program was well-tolerated with all participants in the intervention group completing 4 weeks of training three times a week without any adverse effects. After immersive cognitive motor training, the experimental group made clinically relevant improvements in gait speed and walking distance during the 6 MWT while members of the control group showed no change or decreased gait speed and walking distance over the 1-month trial. In addition, the experimental group demonstrated significant improvement for the TUG Cognitive ( p = 0.05) and those changes were greater than the control group (between group p = 0.040). The experimental group also improved scores on MoCA ( p = 0.007) and SDMT ( p = 0.01) cognitive outcome measures while the control group did not.
Conclusion
The use of immersive gaming technology to engage specific areas of cognition related to gait is feasible in PD. The treadmill training program paired with a customized interactive video game improved walking velocity in addition to non-significant but consistent improvements in other gait measures and cognitive performance in participants with early to mid-stage PD.
Importance
The protective effects of physical activity (PA) against Parkinson disease (PD) development have been suggested; however, the association of PA with mortality in PD has rarely been investigated.
Objective
To evaluate the association between PA and mortality in individuals with PD and determine how the amount and maintenance of PA are associated with mortality.
Design, Setting, and Participants
This nationwide population-based cohort study used Korean National Health Insurance System data. Participants were included from January 1, 2010, and December 31, 2013, and were followed up until December 31, 2017. Data were analyzed from September 2020 to March 2021. Individuals who were newly diagnosed with PD were selected using the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code G20 and registration code V124 in the program for rare intractable diseases in 2010 through 2013. Individuals who underwent health checkups within 2 years before and after the PD diagnosis were enrolled. Those aged younger than 40 years or with missing data were excluded.
Exposures
Physical activity levels were collected using self-reported questionnaires.
Main Outcomes and Measures
All-cause mortality.
Results
A total of 45 923 individuals were identified; 10 987 were enrolled, and 34 individuals younger than 40 years and 254 with missing data were excluded. A total of 10 699 individuals with PD were included; 4925 (46%) were male and 5774 (54%) were female, and the mean (SD) age was 69.2 (8.8) years. During the 8-year follow-up period, there were 1823 deaths (17%). The mortality rate was lower among individuals who were physically active vs inactive at all PA intensities (vigorous: hazard ratio [HR], 0.80 [95% CI, 0.69-0.93]; moderate: HR, 0.66 [95% CI, 0.55-0.78]; light: HR, 0.81 [95% CI, 0.73-0.90]). There was a significant inverse dose-response association between the total amount of PA and mortality (HRs: vigorous, 0.80 [95% CI, 0.69-0.93]; moderate, 0.66 [95% CI, 0.55-0.78]; light, 0.81 [95% CI, 0.73-0.90]; P < .001). Moreover, maintenance of PA was associated with the mortality rate. Individuals with PD who were physically active both before and after the PD diagnosis had the greatest reduction in mortality rate across all PA intensities (HRs: vigorous, 0.66 [95% CI, 0.50-0.88]; moderate, 0.49 [95% CI, 0.32-0.75]; light, 0.76 [95% CI, 0.66-0.89]). Individuals who started PA after receiving the PD diagnosis had a lower mortality rate than those who remained physically inactive (HRs: vigorous, 0.82 [95% CI, 0.70-0.97]; moderate, 0.69 [95% CI, 0.57-0.83]; light, 0.86 [95% CI, 0.78-0.98]).
Conclusions and Relevance
This analysis found a dose-response association between PA and all-cause mortality in PD. Reverse causality may exist, and future prospective randomized clinical trials are warranted to determine the effect of PA on mortality in PD.
Background
Cognitive impairment is among the most burdensome non-motor symptoms in Parkinson’s Disease (PD) and has been associated with hippocampal atrophy. Exercise has been reported to enhance neuroplasticity in the hippocampus in correlation with an improvement of cognitive function. We here present data of the Training-PD study, which was designed to evaluate effects of an Exergaming training protocol on neuronal plasticity in PD.
Methods
We performed a six-week Exergaming training, combining visual stimulating computer games with sportive exercises in n = 17 PD patients and n = 18 matched healthy controls. Volumetric segmentation of hippocampal subfields in T1- and T2-weighted MRI images and BDNF serum levels were analyzed before and after the training protocol.
Results
PD patients showed a group-dependent significant volume increase of the left hippocampal subfields CA1, CA4/Dentate gyrus (DG) and Subiculum after the six-week training protocol. The effect was most pronounced in the left DG of PD patients, who showed a significant smaller percentual volume compared to healthy controls at baseline, but not at follow-up. Both groups showed a significant increase of serum BDNF levels after training.
Conclusions
This study indicates that Exergaming might be a suitable approach to induce hippocampal volume changes in PD patients. Further and larger studies need to verify our findings.
Introducción: La enfermedad de Parkinson (EP) es un trastorno progresivo del movimiento, neurodegenerativo caracterizado por: bradicinesia, temblor, rigidez e inestabilidad postural. Estos síntomas son asociados con trastornos no motores, síntomas neuroconductuales y disminución de la calidad de vida. Entre los tratamientos de rehabilitación para la EP se encuentra la hidroterapia, la cual ofrece ventajas mecánicas específicas y que al ser realizada en una piscina climatizada, además de proporcionar un ambiente cálido es considerada como una de las alternativas de intervención que brinda grandes beneficios a corto y largo plazo en la mejora de las habilidades motoras e incremento de la funcionalidad en las personas con EP. Objetivo: Realizar una revisión documental sobre los beneficios de la hidroterapia en la EP y en el tratamiento neurorehabilitador de la enfermedad. Método: Se efectuó una búsqueda de evidencia en bases de datos como Cochrane, Medline, Pubmed, Scopus, Science Direct, entre los años 2009 y 2020 con las siguientes palabras clave: Enfermedad de Parkinson, hidroterapia, rehabilitación neurológica, neuroplasticidad y dopamina. Resultados: Los estudios mostraron que la hidroterapia como tratamiento neurorehabilitador de la EP es efectiva y además proporciona efectos a corto y largo plazo en la ralentización de los síntomas motores, incrementando la funcionalidad y mejorando la calidad de vida. Conclusión: La hidroterapia a través de los efectos ocasionados por el ejercicio produjo mejoras en el cerebro lesionado del individuo con EP a través de la formación de nuevas redes y circuitos neuronales, abriendo campo a nuevos procesos de aprendizaje motor.
Background: Exercise has been shown to be beneficial for people with Parkinson’s (PwP), slowing the rate of decline of motor and non-motor symptoms, with emerging evidence associating exercise with a neuroprotective effect. Current exercise provision is time-limited, and delivered in the absence of strategies to support long-term adherence to exercise. With a growing Parkinson’s population, there is a need to develop long-term sustainable approaches to exercise delivery. The primary aim of this study is to assess the feasibility and acceptability of a multicomponent intervention (PDConnect) aimed at promoting physical activity, and self-management for PwP.
Methods: A convergent fixed parallel mixed methods design study will be undertaken. The study aims to recruit 30 PwP, who will be randomly allocated into two groups: (i) the usual care group will receive physiotherapy once a week for six weeks delivered via Microsoft Teams. (ii) The PDConnect group will receive physiotherapy once a week for six weeks which combines exercise, education and behaviour change interventions delivered by NHS Parkinson’s specialist physiotherapists via Microsoft Teams. This will be followed by 12 weekly sessions of group exercise delivered on Microsoft Teams by fitness instructors specially trained in Parkinson’s. Participants will be then contacted by the fitness instructors once per month for three months by video conferencing to support exercise engagement. Primary feasibility data will be collected during the study, with acceptability assessed via semi-structured interviews at the end. Secondary outcomes encompassing motor, non-motor and health and well-being measures will be assessed at baseline, at six, 18, and 30 weeks.
Discussion: This pilot study will establish whether PDConnect is feasible and acceptable to PwP. This will provide a platform for a larger evaluation to assess the effectiveness of PDConnect at increasing exercise participation and self-management within the Parkinson’s Community.
Trial registration: Registered on ISRCTN ( ISRCTN11672329 , 4 th June 2020).
Advances in medical management of Parkinson's disease (PD) have resulted in living longer with disability. Although disability worsens over the course of the disease, there are signs of disability even in the early stages. Several studies reveal an early decline in gait and balance and a high prevalence of nonmotor signs in the prodromal period that contribute to early disability. There is a growing body of evidence revealing the benefits of physical therapy and exercise to mitigate motor and nonmotor signs while improving physical function and reducing disability. The presence of early disability coupled with the benefits of exercise suggests that physical therapy should be initiated earlier in the disease. In this review, we present the evidence revealing early disability in PD and the effectiveness of physical therapy and exercise, followed by a discussion of a secondary prevention model of rehabilitation to reduce early disability and optimize long-term outcomes.
Background: Exercise has been shown to be beneficial for people with Parkinson’s (PwP), limiting the rate of decline of motor and non-motor symptoms, with emerging evidence associating exercise with a neuroprotective effect. Current exercise provision is time-limited, and delivered in the absence of strategies to support long-term adherence to exercise. With a growing Parkinson’s population, there is a need to develop long-term sustainable approaches to exercise delivery. The primary aim of this study is to assess the feasibility and acceptability of a multicomponent intervention (PDConnect) aimed at promoting physical activity, and self-management for PwP.
Methods: A convergent fixed parallel mixed methods design study will be undertaken. The study aims to recruit 30 PwP, who will be randomly allocated into two groups: (i) the usual care group will receive physiotherapy once a week for six weeks delivered via Microsoft Teams. (ii) The PDConnect group will receive physiotherapy once a week for six weeks which combines exercise, education and behaviour change interventions delivered by NHS Parkinson’s specialist physiotherapists via Microsoft Teams. This will be followed by 12 weekly sessions of group exercise delivered on Microsoft Teams by fitness instructors specially trained in Parkinson’s. Participants will be then contacted by the fitness instructors once per month for three months by video conferencing to support exercise engagement. Primary feasibility data will be collected during the study, with acceptability assessed via semi-structured interviews at the end. Secondary outcomes encompassing motor, non-motor and health and well-being measures will be assessed at baseline, at six, 18, and 30 weeks.
Discussion: This pilot study will establish whether PDConnect is feasible and acceptable to PwP. This will provide a platform for a larger evaluation to assess the effectiveness of PDConnect at increasing exercise participation and self-management within the Parkinson’s Community.
Trial registration: Registered on ISRCTN ( ISRCTN11672329 , 4 th June 2020).
DNA methylation programs gene expression and is involved in numerous biological processes. Accumulating evidence supports transgenerational inheritance of DNA methylation changes in mammals via germ cells. Our aim was to determine the effect of exercise on sperm DNA methylation.
Twenty-four men were recruited and assigned to an exercise intervention or control group. Clinical parameters were measured and sperm samples were donated by subjects before and after the 3-month time-period. Mature sperm global and genome-wide DNA methylation was assessed using an ELISA assay and the 450K BeadChip (Illumina).
Global and genome-wide sperm DNA methylation was altered after 3 months of exercise training. DNA methylation changes occurred in genes related to numerous diseases such as Schizophrenia and Parkinson's disease.
Our study provides the first evidence showing exercise training reprograms the sperm methylome. Whether these DNA methylation changes are inherited to future generations warrants attention.
Parkinson’s disease (PD) patients, besides motor dysfunctions, may also display mild cognitive deficits (MCI) which increase with disease progression. The neurotrophin brain-derived neurotrophic factor (BDNF) plays a role in the survival of dopaminergic neurons and in the regulation of synaptic connectivity. Moreover, the brain and peripheral level of this protein may be significantly reduced in PD patients. These data suggest that a cognitive rehabilitation protocol aimed at restoring cognitive deficits in PD patients may also involve changes in this neurotrophin. Thus, in this pilot study we evaluated the effect of a cognitive rehabilitation protocol focused on the training of executive functioning and measured BDNF serum levels in a group of PD patients with mild cognitive impairment, as compared to the effect of a placebo treatment (n = 7/8 group). The results showed that PD patients undergoing the cognitive rehabilitation, besides improving their cognitive performance as measured with the Zoo Map Test, also displayed increased serum BDNF levels as compared to the placebo group. These findings suggest that BDNF serum levels may represent a biomarker of the effects of cognitive rehabilitation in PD patients affected by MCI. However, the functional significance of this increase in PD as well as other neuropathological conditions remains to be determined.
Objective
This paper reviews the therapeutically beneficial effects of progressive resistance exercise training (PRET) on motor and nonmotor symptoms in Parkinson's disease (PD).
Methods
First, we perform a systematic review of the literature on the effects of PRET on motor signs of PD, functional outcomes, quality of life, and patient perceived improvement, strength, and cognition in PD. Second, we perform a meta-analysis on the motor section of the UPDRS. Finally, we discuss the results of our review and we identify current knowledge gaps regarding PRET in PD.
Conclusion
This systematic review synthesizes evidence that PRET can improve strength and motor signs of Parkinsonism in PD and may also be beneficial for physical function in individuals with PD. Further research is needed to explore the effects of PRET on nonmotor symptoms such as depression, cognitive impairment, autonomic nervous system dysfunction, and quality of life in individuals with PD.
Objective:
To examine the effects of cycloergometric interval training on parkinsonian rigidity, relaxed biceps brachii muscle tone in affected upper extremities, and serum level of brain-derived neurotrophic factor.
Design:
Case series, repeated-measures design, pilot study.
Subjects/patients:
Eleven patients with mild-to-moderate Parkinson's disease (Hoehn & Yahr scale 2.3 ± 0.72), recruited from a neurological clinic, underwent cycle training and were tested along with non-trained, healthy control subjects (n = 11) in a motor control laboratory.
Methods:
Patients underwent 8 weeks of interval training (3 × 1-h sessions weekly, consisting of a 10-min warm-up, 40 min of interval exercise, and 10-min cool-down) on a stationary cycloergometer. Parkinsonian rigidity (Unified Parkinson's Disease-Rating-Scale) in the upper extremity, resting biceps brachii muscle tone (myometric stiffness and frequency), and brain-derived neurotrophic factor level were measured 1-3 days before interval training cycle started and 6-10 days after the last training session.
Results:
Training resulted in a decrease in rigidity (p = 0.048) and biceps brachii myometric muscle stiffness (p = 0.030) and frequency (p = 0.006), and an increase in the level of brain-derived neurotrophic factor (p = 0.035) relative to pre-training values. The increase in brain-derived neurotrophic factor level correlated with improvements in parkinsonian rigidity (p = 0.025), biceps brachii myometric stiffness (p = 0.001) and frequency (p = 0.002).
Conclusion:
Training-induced alleviation of parkinsonian rigidity and muscle tone decrease may be associated with neuroplastic changes caused by a training-induced increase in the level of brain-derived neurotrophic factor.
Background:
Despite the benefits of medications and surgical interventions for Parkinson's disease (PD), these treatments are not without complications and neuroprotective strategies are still lacking. Therefore, there is a need for effective alternative approaches to treat motor and non-motor symptoms in PD. During the last decade, several studies have investigated endurance exercise training as a potential treatment for individuals with PD.
Objective:
This paper reviews the therapeutically beneficial effects of endurance exercise training on motor and non-motor symptoms in PD.
Methods:
First, we performed a systematic review of the literature on the effects of endurance exercise training on motor and non-motor signs of parkinsonism, functional outcomes including gait, balance and mobility, depression and fatigue, quality of life and perceived patient improvement, cardiorespiratory function, neurophysiological measures, and motor control measures in PD. Second we performed a meta-analysis on the motor section of the UPDRS. Then, we focused on several important factors to consider when prescribing endurance exercise training in PD such as intensity, duration, frequency, specificity and type of exercise. In addition, we identified current knowledge gaps regarding endurance exercise training in PD and made suggestions for future research.
Results:
A total of eight randomized controlled trials met the inclusion criteria and were reviewed. This systematic review synthesizes evidence that endurance exercise training at a sufficiently high level enhances cardiorespiratory capacity and endurance by improving VO2 max and gait in moderately to mildly affected individuals with PD. However, there is not yet a proven effect of endurance exercise training on specific features of PD such as motor signs of parkinsonism.
Conclusion:
Endurance exercise training improves physical conditioning in PD patients; however, to date, there is insufficient evidence to include endurance exercise training as a specific treatment for PD. There is a need for well-designed large-scale randomized controlled trials to confirm benefits and safety of endurance exercise training in PD and to explore potential benefits on the motor and non-motor signs of PD.
It has been demonstrated that physical training increases serum brain-derived neurotrophic factor (BDNF) in healthy people. The aim of this study was to establish the effect of physical training on the basal serum level of the BDNF in the Parkinson's disease patients (PD patients) in relation to their health status. Twelve PD patients (mean ± S.E.M: age 70 ± 3 years; body mass 70 ± 2 kg; height 163 ± 3 cm) performed a moderate-intensity interval training (three 1-hour training sessions weekly), lasting 8 weeks. Basal serum BDNF in the PD patients before training amounted to 10,977 ± 756 pg x mL(-1) and after 8 weeks of training it has increased to 14,206 ± 1256 pg x mL(-1) (i.e. by 34%, P=0.03). This was accompanied by an attenuation of total Unified Parkinson's Disease Rating Scale (UPDRS) (P=0.01). The training resulted also in a decrease of basal serum soluble vascular cell adhesion molecule 1 (sVCAM-1) (P=0.001) and serum tumor necrosis factor-α (TNF-α) (P=0.03) levels. We have concluded that the improvement of health status of the Parkinson's disease patients after training could be related to the increase of serum BDNF level caused by the attenuated inflammation in those patients.
Background. Exercise may decrease the risk of Parkinson’s disease (PD) in humans and reduce PD symptoms in animal
models. The beneficial effects have been linked to increased levels of neurotrophic factors. Objective. We examined whether
intensive rehabilitation treatment reduces motor disability in patients in the early stages of PD and increases brain-derived
neurotrophic factor (BDNF) serum levels. Methods. Thirty participants in the early stages of PD treated with rasagiline
were randomly assigned to 3 hours of rehabilitation treatment that included aerobic exercise for 28 days (Group 1) or to
not therapy (control; Group 2). BDNF serum levels were assessed at time T0 (baseline, before treatment), T1 (10 days),
T2 (20 days), and T3 (28 days). At T0 and T3, we assessed the Unified Parkinson’s Disease Rating Scale (UPDRS) III in both
groups, as well as the UPDRS II and total, Berg Balance Scale, and 6-minute walking test only in Group 1. Results. BDNF
levels significantly increased at T1 in Group 1, an increase that was maintained throughout the treatment period. At T3
compared to T0, UPDRS III scores significantly improved in Group 1 along with scores for UPDRS II, total, Berg Balance
Scale, and 6-minute walking test. Conclusions. Intensive rehabilitation treatment increases the BDNF levels and improves
PD signs in patients in the early stages of the disease. These results are in line with studies on animal models of PD and
healthy subjects.
The objective was to update previous evidence-based medicine reviews of treatments for motor symptoms of Parkinson's disease published between 2002 and 2005. Level I (randomized, controlled trial) reports of pharmacological, surgical, and nonpharmacological interventions for the motor symptoms of Parkinson's disease between January 2004 (2001 for nonpharmacological) and December 2010 were reviewed. Criteria for inclusion, clinical indications, ranking, efficacy conclusions, safety, and implications for clinical practice followed the original program outline and adhered to evidence-based medicine methodology. Sixty-eight new studies qualified for review. Piribedil, pramipexole, pramipexole extended release, ropinirole, rotigotine, cabergoline, and pergolide were all efficacious as symptomatic monotherapy; ropinirole prolonged release was likely efficacious. All were efficacious as a symptomatic adjunct except pramipexole extended release, for which there is insufficient evidence. For prevention/delay of motor fluctuations, pramipexole and cabergoline were efficacious, and for prevention/delay of dyskinesia, pramipexole, ropinirole, ropinirole prolonged release, and cabergoline were all efficacious, whereas pergolide was likely efficacious. Duodenal infusion of levodopa was likely efficacious in the treatment of motor complications, but the practice implication is investigational. Entacapone was nonefficacious as a symptomatic adjunct to levodopa in nonfluctuating patients and nonefficacious in the prevention/delay of motor complications. Rasagiline conclusions were revised to efficacious as a symptomatic adjunct, and as treatment for motor fluctuations. Clozapine was efficacious in dyskinesia, but because of safety issues, the practice implication is possibly useful. Bilateral subthalamic nucleus deep brain stimulation, bilateral globus pallidus stimulation, and unilateral pallidotomy were updated to efficacious for motor complications. Physical therapy was revised to likely efficacious as symptomatic adjunct therapy. This evidence-based medicine review updates the field and highlights gaps for research. © 2011 Movement Disorder Society
Cognitive abnormalities are a feature of Parkinson's disease (PD). Unlike motor symptoms that are clearly improved by dopaminergic therapy, the effect of dopamine replacement on cognition seems paradoxical. Some cognitive functions are improved whereas others are unaltered or even hindered. Our aim was to understand the effect of dopamine replacement therapy on various aspects of cognition. Whereas dorsal striatum receives dopamine input from the substantia nigra (SN), ventral striatum is innervated by dopamine-producing cells in the ventral tegmental area (VTA). In PD, degeneration of SN is substantially greater than cell loss in VTA and hence dopamine-deficiency is significantly greater in dorsal compared to ventral striatum. We suggest that dopamine supplementation improves functions mediated by dorsal striatum and impairs, or heightens to a pathological degree, operations ascribed to ventral striatum. We consider the extant literature in light of this principle. We also survey the effect of dopamine replacement on functional neuroimaging in PD relating the findings to this framework. This paper highlights the fact that currently, titration of therapy in PD is geared to optimizing dorsal striatum-mediated motor symptoms, at the expense of ventral striatum operations. Increased awareness of contrasting effects of dopamine replacement on dorsal versus ventral striatum functions will lead clinicians to survey a broader range of symptoms in determining optimal therapy, taking into account both those aspects of cognition that will be helped versus those that will be hindered by dopaminergic treatment.
The brain-derived neurotrophic factor (BDNF) is a potent inhibitor of apoptosis-mediated cell death and neurotoxin-induced degeneration of dopaminergic neurons. There is a growing body of evidence implicating BDNF in the pathogenesis of Parkinson's disease (PD), suggesting it may eventually be used in the development of neuroprotective therapies for PD. The serum BDNF of 47 PD patients and of 23 control subjects was assessed, and serum BNDF levels were significantly decreased in PD patients when compared with controls (p = 0.046). Interestingly enough, BDNF correlated positively with a longer time span of the disease, as well as with the severity of the PD symptoms and with more advanced stages of the disease. Additionally, higher BDNF levels also correlated with poor balance as assessed by the Berg Balance Scale, more time spent at the Timed Up & Go Test, reduced speed of gait and shorter distance walked during the Six-Minute Walk Test. Our results corroborate the literature regarding the involvement of BDNF in PD. We hypothesize that lower BDNF levels in early stages of the disease may be associated with pathogenic mechanisms of PD. The increase of BDNF levels with the progression of the disease may be a compensatory mechanism in more advanced stages of PD.
Since the purification of BDNF in 1982, a great deal of evidence has mounted for its central roles in brain development, physiology, and pathology. Aside from its importance in neural development and cell survival, BDNF appears essential to molecular mechanisms of synaptic plasticity. Basic activity-related changes in the central nervous system are thought to depend on BDNF modification of synaptic transmission, especially in the hippocampus and neocortex. Pathologic levels of BDNF-dependent synaptic plasticity may contribute to conditions such as epilepsy and chronic pain sensitization, whereas application of the trophic properties of BDNF may lead to novel therapeutic options in neurodegenerative diseases and perhaps even in neuropsychiatric disorders.
Studies have suggested that there are beneficial effects of exercise in patients with Parkinson's disease, but the underlying molecular mechanisms responsible for these effects are poorly understood. Studies in rodent models provide a means to examine the effects of exercise on dopaminergic neurotransmission. Using intensive treadmill exercise, we determined changes in striatal dopamine in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse. C57BL/6J mice were divided into four groups: (1) saline, (2) saline plus exercise, (3) MPTP, and (4) MPTP plus exercise. Exercise was started 5 d after MPTP lesioning and continued for 28 d. Treadmill running improved motor velocity in both exercise groups. All exercised animals also showed increased latency to fall (improved balance) using the accelerating rotarod compared with nonexercised mice. Using HPLC, we found no difference in striatal dopamine tissue levels between MPTP plus exercise compared with MPTP mice. There was an increase detected in saline plus exercise mice. Analyses using fast-scan cyclic voltammetry showed increased stimulus-evoked release and a decrease in decay of dopamine in the dorsal striatum of MPTP plus exercise mice only. Immunohistochemical staining analysis of striatal tyrosine hydroxylase and dopamine transporter proteins showed decreased expression in MPTP plus exercise mice compared with MPTP mice. There were no differences in mRNA transcript expression in midbrain dopaminergic neurons between these two groups. However, there was diminished transcript expression in saline plus exercise compared with saline mice. Our findings suggest that the benefits of treadmill exercise on motor performance may be accompanied by changes in dopaminergic neurotransmission that are different in the injured (MPTP-lesioned) compared with the noninjured (saline) nigrostriatal system.
Since 2013, a number of studies have enhanced the literature and have guided clinicians on viable treatment interventions outside of pharmacotherapy and surgery. Thirty-three randomized controlled trials and one large observational study on exercise and physiotherapy were published in this period. Four randomized controlled trials focused on dance interventions, eight on treatment of cognition and behavior, two on occupational therapy, and two on speech and language therapy (the latter two specifically addressed dysphagia). Three randomized controlled trials focused on multidisciplinary care models, one study on telemedicine, and four studies on alternative interventions, including music therapy and mindfulness. These studies attest to the marked interest in these therapeutic approaches and the increasing evidence base that places nonpharmacological treatments firmly within the integrated repertoire of treatment options in Parkinson's disease. © 2015 International Parkinson and Movement Disorder Society.
© 2015 Movement Disorder Society.
Backgroud
There is substantial interest in the impact of exercise on reduction of disability and rate of progression of Parkinson’s disease (PD).
Objective
The primary aim was to describe exercise habits of PD patients and factors associated with greater levels of exercise. The secondary aim was to explore whether regular exercise is associated with a slower decline of function, disease-related quality of life, and caregiver burden.
Methods
The National Parkinson’s Foundation (NPF) Registry data was used to analyze variables that correlate with levels of exercise in PD patients across disease severity. Subjects were categorized into three groups: non-exercisers (0 min/week), low exercisers (1-150 min/week), and regular exercisers (>150 min/week). Health related outcomes, disease metrics, and demographic factors associated with exercise were examined using bivariate analyses. Multiple regression models controlled for disease duration, severity, and cognitive function. An exploratory analysis was completed on the association of baseline level of exercise with health outcomes at one year follow up.
Results
4866 subjects were included in the baseline analysis and 2252 subjects who had second visits were included in the longitudinal data. Regular exercisers at baseline was associated with better QOL, mobility, and physical function, less progression of disease, less caregiver burden and less cognitive decline one year later, after controlling for demographic and disease severity variables.
Conclusions
This study provides important preliminary evidence of the beneficial effects of regular exercise in a large PD cohort. Longitudinal studies will be essential to confirm findings.
Purpose of review:
Later stage Parkinson's disease, sometimes referred to as advanced disease, has been characterized by motor complication, as well as by the potential emergence of nonlevodopa responsive motor and nonmotor symptoms. The management of advanced stage Parkinson's disease can be complex. This review summarizes the currently available treatment strategies for addressing advanced Parkinson's disease.
Recent findings:
We will discuss the latest pharmacological strategies (e.g., inhibitors of dopamine-metabolizing enzymes, dopamine agonists, and extended release dopamine formulations) for addressing motor dysfunction. We will summarize the risks and benefits of current invasive treatments. Finally, we will address the current evidence supporting the treatment of nonmotor symptoms in the advanced Parkinson's disease patient. We will conclude by detailing the potential nonpharmacological and multidisciplinary approaches for advanced stage Parkinson's disease.
Summary:
The optimization of levodopa is, in most cases, the most powerful therapeutic option available; however, medication optimization requires an advanced understanding of Parkinson's disease. Failure of conventional pharmacotherapy should precipitate a discussion of the potential risks and benefits of more invasive treatments. Currently, there are no comparative studies of invasive treatment. Among the invasive treatments, deep brain stimulation has the largest amount of existing evidence, but also has the highest individual per patient risk. Nonmotor symptoms will affect quality of life more than the motor Parkinson's disease symptoms, and these nonmotor symptoms should be aggressively treated. Many advanced Parkinson's disease patients will likely benefit from multi and interdisciplinary Parkinson's disease teams with multiple professionals collaborating to develop a collective and tailored strategy for an individual patient.
Purpose of review:
This review summarizes currently available treatment options and treatment strategies, investigational treatments, and the importance of exercise for early Parkinson's disease.
Recent findings:
The available treatment options for early Parkinson's disease have changed little in the past decade and include carbidopa/levodopa, dopamine agonists, and monoamine oxidase type B (MAO-B) inhibitors. However, we discuss changes in treatment strategies, including dosing and the use of combination therapy used in an attempt to reduce or delay the appearance of motor complications and other adverse events. We will also review several investigational treatments that have shown promise for the treatment of early Parkinson's disease, including a new extended release formulation of carbidopa/levodopa (IPX066), safinamide which inhibits MAO-B, dopamine uptake and glutamate and pardoprunox which is a 5HT-1A agonist and a partial dopamine agonist. Finally, we discuss recent studies focusing on exercise as an important component in the management of early Parkinson's disease.
Summary:
Advances in the management of early Parkinson's disease include evolving treatment strategies, new investigational treatments, and earlier implementation of various forms of exercise.
Exercise interventions in individuals with Parkinson's disease incorporate goal-based motor skill training to engage cognitive circuitry important in motor learning. With this exercise approach, physical therapy helps with learning through instruction and feedback (reinforcement) and encouragement to perform beyond self-perceived capability. Individuals with Parkinson's disease become more cognitively engaged with the practice and learning of movements and skills that were previously automatic and unconscious. Aerobic exercise, regarded as important for improvement of blood flow and facilitation of neuroplasticity in elderly people, might also have a role in improvement of behavioural function in individuals with Parkinson's disease. Exercises that incorporate goal-based training and aerobic activity have the potential to improve both cognitive and automatic components of motor control in individuals with mild to moderate disease through experience-dependent neuroplasticity. Basic research in animal models of Parkinson's disease is beginning to show exercise-induced neuroplastic effects at the level of synaptic connections and circuits.
We have previously demonstrated changes in dopaminergic neurotransmission after intensive exercise in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse model of Parkinson's disease (PD), including an increase in the dopamine D2 receptor (DA-D2R), using noninvasive PET imaging with the radioligand [F]fallypride. The purpose of this feasibility and translational study was to examine whether intensive exercise leads to similar alterations in DA-D2R expression using PET imaging with [F]fallypride in individuals with early-stage PD. In this pilot study, four patients with early-stage PD were randomized to receive intensive exercise (treadmill training sessions three times/week for 8 weeks) or no exercise. Two healthy age-matched individuals participated in treadmill training. Alterations in the DA-D2R binding potential (BP) as a marker for receptor expression were determined using PET imaging with [F]fallypride. Turning performance in the patients with PD as a measure of postural control and the Unified Parkinson's Disease Rating Scale scores pre-exercise and postexercise were determined. Our data showed an exercise-induced increase in [F]fallypride BP as well as improved postural control in patients with PD who exercised. Changes in DA-D2R BP were not observed in patients with PD who did not exercise. These results suggest that exercise can lead to neuroplasticity in dopaminergic signaling and contribute to improved function that may be task specific (postural control) in early-stage PD.
Physical exercise is known to produce beneficial effects to the nervous system. In most cases, brain-derived neurotrophic factor (BDNF) is involved in such effects. However, little is known on the role of BDNF in exercise-related effects on Parkinson's disease (PD). The aim of this study was to investigate the effects of intermittent treadmill exercise-induced behavioral and histological/neurochemical changes in a rat model of unilateral PD induced by striatal injection of 6-hydroxydopamine (6-OHDA), and the role of BDNF in the exercise effects. Adult male Wistar rats were divided into two main groups: (1) injection of K252a (a blocker of BDNF receptors), and (2) without BDNF receptor blockade. These groups were then subdivided into four groups: control (CLT), sedentary (SED, non-exercised with induction of PD), exercised 3x/week during four weeks before and four weeks after the induction of PD (EXB+EXA), and exercised 3x/week during four weeks after the induction of PD (EXA). One month after 6-OHDA injections, the animals were subjected to rotational behavioral test induced by apomorphine and the brains were collected for immunohistochemistry and immunoblotting assays, in which we measured BDNF and tyrosine hydroxylase (TH) in the substantia nigra pars compacta (SNc) and the striatum (caudate-putamen, CPu). Our results showed a significant reduction of rotational asymmetry induced by apomorphine in the exercised parkinsonian rats. BDNF decreased in the SNc of the SED group, and exercise was able to revert that effect. Exercised groups exhibited reduced damage to the dopaminergic system, detected as a decreased drop of TH levels in SNc and CPu. On the other hand, BDNF blockade was capable of substantially reducing TH expression postlesion, implying enhanced dopaminergic cell loss. Our data revealed that physical exercise is capable of reducing the damage induced by 6-OHDA, and that BDNF receptors are involved in that effect.
Since the purification of BDNF in 1982, a great deal of evidence has mounted for its central roles in brain development, physiology, and pathology. Aside from its importance in neural development and cell survival, BDNF appears essential to molecular mechanisms of synaptic plasticity. Basic activity-related changes in the central nervous system are thought to depend on BDNF modification of synaptic transmission, especially in the hippocampus and neocortex. Pathologic levels of BDNF-dependent synaptic plasticity may contribute to conditions such as epilepsy and chronic pain sensitization, whereas application of the trophic properties of BDNF may lead to novel therapeutic options in neurodegenerative diseases and perhaps even in neuropsychiatric disorders.
Despite medical therapies and surgical interventions for Parkinson's disease (PD), patients develop progressive disability. The role of physiotherapy aims to maximise functional ability and minimise secondary complications through movement rehabilitation within a context of education and support for the whole person. The overall aim is to optimise independence, safety and well-being, thereby enhancing quality of life.
To assess the effectiveness of physiotherapy intervention compared with no intervention in patients with PD.
We identified relevant trials by electronic searches of numerous literature databases (e.g. MEDLINE, EMBASE) and trial registers, plus handsearching of major journals, abstract books, conference proceedings and reference lists of retrieved publications. The literature search included trials published up to end of December 2010.
Randomised controlled trials of physiotherapy intervention versus no physiotherapy intervention in patients with PD.
Two review authors independently extracted data from each article. We used standard meta-analysis methods to assess the effectiveness of physiotherapy intervention compared with no physiotherapy intervention. Trials were classified into the following intervention comparisons: general physiotherapy, exercise, treadmill training, cueing, dance and martial arts. We used tests for heterogeneity to assess for differences in treatment effect across these different physiotherapy interventions.
We identified 33 trials with 1518 participants. Compared with no-intervention, physiotherapy significantly improved the gait outcomes of velocity (mean difference 0.05 m/s, 95% confidence interval (CI): 0.02 to 0.07, P = 0.0002), two- or six-minute walk test (16.40 m, CI: 1.90 to 30.90, P = 0.03) and step length (0.03 m, CI: 0 to 0.06, P = 0.04); functional mobility and balance outcomes of Timed Up & Go test (-0.61 s, CI: -1.06 to -0.17, P = 0.006), Functional Reach Test (2.16 cm, CI: 0.89 to 3.43, P = 0.0008) and Berg Balance Scale (3.36 points, CI: 1.91 to 4.81, P < 0.00001); and clinician-rated disability using the Unified Parkinson's Disease Rating Scale (UPDRS) (total: -4.46 points, CI -7.16 to -1.75, P = 0.001; activities of daily living: -1.36, CI -2.41 to -0.30, P = 0.01; and motor: -4.09, CI: -5.59 to -2.59, P < 0.00001). There was no difference between arms in falls or patient-rated quality of life. Indirect comparisons of the different physiotherapy interventions found no evidence that the treatment effect differed across the physiotherapy interventions for any of the outcomes assessed.
Benefit for physiotherapy was found in most outcomes over the short-term (i.e. < three months), but was only significant for velocity, two- or six-minute walk test, step length, Timed Up & Go, Functional Reach Test, Berg Balance Scale and clinician-rated UPDRS. Most of the observed differences between the treatments were small. However, for some outcomes (e.g. velocity, Berg Balance Scale and UPDRS), the differences observed were at, or approaching, what are considered minimally clinical important changes.The review illustrates that a wide range of approaches are employed by physiotherapists to treat PD. However, there was no evidence of differences in treatment effect between the different types of physiotherapy interventions being used, though this was based on indirect comparisons. There is a need to develop a consensus menu of 'best-practice' physiotherapy, and to perform large well-designed randomised controlled trials to demonstrate the longer-term efficacy and cost-effectiveness of 'best practice' physiotherapy in PD.
Commuting by bike has a clear health enhancing effect. Moreover, regular exercise is known to improve brain plasticity, which results in enhanced cognition and memory performance. Animal research has clearly shown that exercise upregulates brain-derived neurotrophic factor (BDNF - a neurotrophine) enhancing brain plasticity. Studies in humans found an increase in serum BDNF concentration in response to an acute exercise bout. Recently, more evidence is emerging suggesting that exposure to air pollution (such as particulate matter (PM)) is higher in commuter cyclists compared to car drivers. Furthermore, exposure to PM is linked to negative neurological effects, such as neuroinflammation and cognitive decline. We carried-out a cross-over experiment to examine the acute effect of exercise on serum BDNF, and the potential effect-modification by exposure to traffic-related air pollution. Thirty eight physically fit, non-asthmatic volunteers (mean age: 43, 26% women) performed two cycling trials, one near a major traffic road (Antwerp Ring, R1, up to 260,000 vehicles per day) and one in an air-filtered room. The air-filtered room was created by reducing fine particles as well as ultrafine particles (UFP). PM10, PM2.5 and UFP were measured. The duration (∼20min) and intensity of cycling were kept the same for each volunteer for both cycling trials. Serum BDNF concentrations were measured before and 30min after each cycling trial. Average concentrations of PM10 and PM2.5 were 64.9μg/m(3) and 24.6μg/m(3) in cycling near a major ring way, in contrast to 7.7μg/m(3) and 2.0μg/m(3) in the air-filtered room. Average concentrations of UFP were 28,180 particles/cm(3) along the road in contrast to 496 particles/cm(3) in the air-filtered room. As expected, exercise significantly increased serum BDNF concentration after cycling in the air-filtered room (+14.4%; p=0.02). In contrast, serum BDNF concentrations did not increase after cycling near the major traffic route (+0.5%; p=0.42). Although active commuting is considered to be beneficial for health, this health enhancing effect could be negatively influenced by exercising in an environment with high concentrations of PM. Whether this effect is also present with chronic exercise and chronic exposure must be further elucidated.
Parkinson's disease (PD) is characterized by a progressive and selective loss of dopaminergic (DA) neurons in the substantia nigra (SN). Although the etiology of PD remains unclear, neuroinflammation has been implicated in the development of PD. Running exercise (Ex) promotes neuronal survival and facilitates the recovery of brain functions after injury. Therefore, we hypothesize that Ex protects the DA neurons against inflammation-induced injury in the SN. An intraperitoneal lipopolysaccharide (LPS, 1 mg/kg) injection induced microglia activation in the SN within hours, followed by a reduction in the number of DA neurons. LPS reduced the level of dopamine in the striatum and impaired the performance of motor coordination. Furthermore, the levels of the brain-derived neurotrophic factor (BDNF) were reduced in the SN by the LPS treatment. Four weeks of Ex before LPS treatment completely prevented the LPS-induced loss of DA neurons, reduction of dopamine levels and dysfunction of motor movement. Ex did not change the LPS-induced status of microglia activation or the levels of cytokines/chemokines, but restored the levels of LPS-reduced BDNF-TrkB signaling molecules. Blocking the action of BDNF, through its receptor TrkB antagonist, abolished the Ex-induced protection against LPS-induced DA neuron loss. Intrastriatal perfusion of BDNF alone was sufficient to counteract the LPS-induced DA neuron loss. Altogether, our results show that Ex protects DA neurons against inflammation-induced insults. The neuroprotective effects of Ex are not due to the modulation of inflammation status, but rather to the activation of the BDNF-TrkB signaling pathway.
The distribution of nerve growth factor (NGF), ciliary neurotrophic factor (CNTF), glial cell line-derived neurotrophic factor (GDNF), brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4) in substantia nigra pars compacta (SNc) of Parkinson's disease (PD) brains was investigated by immunofluorescence. Cases studied included four 69-77 year old neurologically normal male controls and four 72-79 year old male PD patients. Integrated optical densities (IODs) of immunofluorescence over individual neuromelanin-containing neurons and in areas of neuropil and the number of neurons on H & E stained adjacent sections were quantitated with the use of the BioQuant Image Analyzer. Data were statistically analyzed by ANOVA, including the unpaired two-tailed Student t-test and the Mann-Whitney test. The results showed 55.8% (P<0.0001) dropout of SNc neurons in PD brains compared to age-matched controls. Despite considerable neuronal dropout, immunofluorescent NTFs in the PD brains showed differential reductions that were consistent within the group as compared to age-matched controls: reductions were GDNF, 19.4%/neuron (P<0.0001), 20.2%/neuropil (P<0.0001); CNTF, 11.1%/neuron (P<0.0001), 9.4%/neuropil (P<0.0001); BDNF, 8.6%/neuron (P<0.0001), 2.5%/neuropil. NGF, NT-3 and NT-4 showed no significant differences within surviving neurons or neuropil. Since the depletion of GDNF both within surviving neurons and neuropil was twice as great as that of CNTF and BDNF and since the other NTFs showed no changes, GDNF, of the tested NTFs, is probably the most susceptible and the earliest to decrease in the surviving neurons of SNc. These observations suggest a role for decreased availability of GDNF in the process of SNc neurodegeneration in PD.
Unilateral administration of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle (MFB) causes a loss of dopamine (DA) in the ipsilateral striatum and contralateral motor deficits. However, if a cast is placed on the ipsilateral limb during the first 7 days following 6-OHDA infusion, forcing the animal to use its contralateral limb, both the behavioral and neurochemical deficits are reduced. Here, we examine the effect of forced reliance on a forelimb during the 7 days prior to ipsilateral infusion of 6-OHDA on the deficits characteristic of this lesion model. Casted animals displayed no behavioral asymmetries as measured 14-28 days postlesion and a marked attenuation in the loss of striatal DA and its metabolites at 30 days. In addition, animals receiving a unilateral cast alone had an increase in glial cell-line derived neurotrophic factor (GDNF) protein in the striatum corresponding to the overused limb. GDNF increased within 1 day after the onset of casting, peaked at 3 days, and returned to baseline within 7 days. These results suggest that preinjury forced limb-use can prevent the behavioral and neurochemical deficits to the subsequent administration of 6-OHDA and that this may be due in part to neuroprotective effects of GDNF.
Idiopathic Parkinson's disease (PD) affects 2% of adults over 50 years of age. PD patients demonstrate a progressive loss of dopamine neurons in the substantia nigra pars compacta (SNpc). One model that recapitulates the pathology of PD is the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Here we show that exposure to an enriched environment (EE) (a combination of exercise, social interactions and learning) or exercise alone during adulthood, totally protects against MPTP-induced Parkinsonism. Furthermore, changes in mRNA expression would suggest that increases in glia-derived neurotrophic factors, coupled with a decrease of dopamine-related transporters (e.g. dopamine transporter, DAT; vesicular monoamine transporter, VMAT2), contribute to the observed neuroprotection of dopamine neurons in the nigrostriatal system following MPTP exposure. This non-pharmacological approach presents significant implications for the prevention and/or treatment of PD.
The adult substantia nigra bears the capacity to generate new neural cells throughout adulthood. The mechanisms of cellular plasticity in this brain region remain unknown. In the adult dentate gyrus, dopamine was suggested to be one of the key players in neurogenesis. We therefore investigated nigral cellular plasticity in the 6-OHDA rat model of Parkinson's disease. The absolute numbers of newborn cells in the SN were not affected by dopamine depletion. Interestingly, we found a specific downregulation of generation of newborn nigral astrocytic cells. As enriched environment with physical activity are robust inducers of neuro- and gliogenesis in the adult DG, we investigated the role of these physiological stimuli in nigral cellular plasticity and in motor behavior of 6-OHDA lesioned rats. We describe a significant increase in numbers of newborn NG2-positive and GFAP-positive cells in the SN. Moreover, 6-OHDA lesioned animals living in enriched environment with physical activity for 7 weeks showed improved motor behavior compared to controls under standard conditions. Thus, physiological neurogenic and gliogenic stimuli induce significant microenvironmental changes in the adult SN and improve motor behavior in the 6-OHDA lesion model of PD.
To obtain preliminary data on the effects of high-intensity exercise on functional performance in people with Parkinson's disease (PD) relative to exercise at low and no intensity and to determine whether improved performance is accompanied by alterations in corticomotor excitability as measured through transcranial magnetic stimulation (TMS).
Cohort (prospective), randomized controlled trial.
University-based clinical and research facilities.
Thirty people with PD, within 3 years of diagnosis with Hoehn and Yahr stage 1 or 2.
Subjects were randomized to high-intensity exercise using body weight-supported treadmill training, low-intensity exercise, or a zero-intensity education group. Subjects in the 2 exercise groups completed 24 exercise sessions over 8 weeks. Subjects in the zero-intensity group completed 6 education classes over 8 weeks.
Unified Parkinson's Disease Rating Scales (UPDRS), biomechanic analysis of self-selected and fast walking and sit-to-stand tasks; corticomotor excitability was assessed with cortical silent period (CSP) durations in response to single-pulse TMS.
A small improvement in total and motor UPDRS was observed in all groups. High-intensity group subjects showed postexercise increases in gait speed, step and stride length, and hip and ankle joint excursion during self-selected and fast gait and improved weight distribution during sit-to-stand tasks. Improvements in gait and sit-to-stand measures were not consistently observed in low- and zero-intensity groups. The high-intensity group showed lengthening in CSP.
The findings suggest the dose-dependent benefits of exercise and that high-intensity exercise can normalize corticomotor excitability in early PD.
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