The Positive Effects of Physical Activity on Quality of Life in Parkinson’s Disease: A Systematic Review

Background: Physical activity can have positive effects on motor and non-motor symptoms in Parkinson’s disease, but its benefits in terms of quality of life and function are uncertain and vary based on the specific forms of activities and interventions. Objective: We sought to assess the current evidence on the positive effects of physical activity in people with Parkinson’s disease and more specifically in relation to its potential benefits for quality of life. Methods: This systematic review was conducted between January and April 2024 via the PubMed, Medline, and Scopus databases. Predetermined search criteria were used that included the following terms: “Parkinson’s disease”, “quality of life” and “physical activity”. Results: A total of 1669 articles were identified. After utilizing predetermined criteria, a total of fifteen articles met the selection criteria. Statistically significant improvements in quality of life were found in seven studies. Seven studies demonstrated a significant improvement in non-motor symptoms, while nine studies showed an improvement in motor symptoms. Conclusions: Despite heterogeneity in the study designs, interventions and clinical assessments, the articles identified in this review yielded mostly positive results in relation to physical activities. The findings reflect an improvement in motor and non-motor symptoms may translate to a better quality of life in people with Parkinson’s disease.


Introduction
Parkinson's disease (PD) is a common neurodegenerative disorder typically characterized by motor symptoms and now increasingly recognized according to a myriad of complex non-motor symptoms (NMS).The latter are often subtle at onset and can occur many years prior to diagnosis [1][2][3][4].With a wide array of symptomatology and the inevitable progression of the disease due to the loss of the dopaminergic neurons residing in the substantia nigra and non-dopaminergic dysfunction, quality of life (QoL) is predictably impacted in PD [5][6][7].Early identification and treatment of symptoms can promote an improvement in the QoL of these individuals [8,9] and whilst management is often individualized as part of best practice, it can be challenging and ideally should encompass both pharmacological and non-pharmacological modalities [10,11].
When examining any purported treatment or procedure and its subsequent benefits or risks in terms of the outcomes for patients, QoL is an established construct used and universally understood to reflect the overall subjective well-being of an individual.It is not only pathophysiology and the manifestation of disease but also an individual's function, satisfaction and contentment experienced in life which form the construct of QoL [12,13].QoL outcomes are useful for attaining evidence of meaningful benefit, enhancing the significance of variables of interest and allowing for more holistic decision-making [12].The link between QoL and physical activity (PA) has increasingly been consolidated in the literature [13], including in PD, whereby many studies have assessed various nonpharmacological interventions.Examples include exercise programs [14], Tai Chi Quan [15] and aquatic physiotherapy [16], which demonstrated an improvement in QoL and wellbeing in individuals with PD.PD-specific instruments have also been developed to assess QoL in this patient group [17][18][19][20][21].
Growing evidence indicates PA can offer tangible improvements in QoL measures for people with PD.The multisystem effects of PD require trials that examine PA and any reported benefits to account for its potential mechanisms, ranging from the simplistic approach of feeling more connected to others to its impact on neuroplasticity [22].
It is thought that exercise may complement standard pharmacological approaches by enhancing neuroplasticity in PD, such as regeneration and the survival of pars compacta neurons [23,24].It is postulated that many neurotrophic factors are influenced by PA.For example, brain-derived neurotrophic factor (BDNF) is stimulated during exercise to mediate neuroprotective effects and is thought to improve cognition and mood [25][26][27].Evidence suggests exercise can positively affect neuroplasticity via various mechanisms that include the up-titration of binding in the dopaminergic pathways [28,29] and inhibition of Lewy body formation in rat models [29].Reducing neurodegeneration via the regulation of autophagy and apoptosis have also been proposed as mechanisms of the benefits of PA [25].
With feasible improvements in both, NMS (in terms of anxiety, cognitive functions and depression) and activities of daily living, exercise has the potential to significantly benefit the overall QoL in people with PD [30].In this review, our defined objective was to assess the current evidence on the positive effects of physical activity in people with Parkinson's disease and, more specifically, in relation to its potential benefit in terms of quality of life.

Literature Search and Selection Criteria
This systematic review was conducted between January and April 2024.The literature search used the guiding question of "Does physical activity positively affect quality of life in people with Parkinson's disease?".Based on a PICO approach, the population of interest comprised people with Parkinson's disease with an interest in the positive effects of physical activity in the context of quality of life.
The terms in the present review, "Parkinson's disease", "quality of life" and "physical activity", were used as search terms in three databases, PubMed, Medical Literature Analysis and Retrieval System Online (Medline) and Scopus, and were cross-checked with the use of Boolean AND.All terms are included in the Medical Subject Headings (MeSH) and Health Sciences Descriptors (DeCS).
The inclusion criteria were as follows: (i) articles published between 1991 and 2024 written in English, Spanish or Portuguese; (ii) randomized interventional studies (level of evidence II) [31], which was specifically chosen to ensure the reliability and validity of the outcomes by minimizing bias; (iii) studies with 10 or more participants diagnosed with idiopathic PD in the intervention group, as well as appropriate evaluation of the effects of physical activity and quality of life.The exclusion criteria comprised the following: (i) studies in animals, letters to the editor or systematic or integrative reviews and (ii) repeated articles in different databases.The different phases of the systematic review are summarized in Figure 1.repeated articles in different databases.The different phases of the systematic review are summarized in Figure 1.Articles were blindly and independently selected by two reviewers, after which the abstracts were read.After that, two more reviewers were added, and the JADAD scale was applied.The JADAD consists of 5 questions that assess the following aspects of clinical trials: randomization, blinding and description of losses to follow-up [32].These measures ensured the reliability and validity of the studies in question.
The protocol for this systematic review was registered with PROSPERO on 25 October 2021.Articles were blindly and independently selected by two reviewers, after which the abstracts were read.After that, two more reviewers were added, and the JADAD scale was applied.The JADAD consists of 5 questions that assess the following aspects of clinical trials: randomization, blinding and description of losses to follow-up [32].These measures ensured the reliability and validity of the studies in question.
The protocol for this systematic review was registered with PROSPERO on 25 October 2021.
As QoL has a global scope, its associated effects on motor symptoms and NMS were considered as secondary outcomes.A diverse array of instruments for assessing the latter were used based on the respective study objectives and variables of interest.Therefore, the following instruments were utilized:

Data Extraction
Data extraction was conducted by one author and confirmed by the co-authors.After applying the inclusion and exclusion criteria, each article was reviewed in detail by two nominated members, with particular interest in the participant demographics, type of PA, frequency, duration and mode of delivery, as well as the effect on QoL.

Results
The selection process identified 1669 articles, of which 980 were excluded due to lack of randomization or because they had not been published between 1991 and 2024.A further 502 articles were excluded following title and abstract screening.The remaining 150 articles were reviewed and resulted in 14 articles meeting the inclusion criteria (see Figure 1-flow diagram).
The selected articles were in their entirety randomized interventional studies published between 2012 and 2024.With respect to the location of the respective studies, five studies were from North America [33][34][35][36][37]; two were from South America: Brazil [38,39]; five were from Europe: Hungary [40], Italy [41], the United Kingdom [42], Germany [43]; The Netherlands [44]; and three were from Asia: the Republic of Korea [30] and Hong Kong [45,46].All of the articles were published in English.

Participants
The number of participants in each study ranged from 20 to 230, with an overall total of 1200 participants (see Table 1).There was a higher male-to-female ratio in all studies apart from three, which had a higher female-to-male ratio [30,45,46].The duration of PD since diagnosis ranged from 1 to 15 years in the selected sample, with the exception of two studies that reported this information at baseline but did not specify disease duration [45,46].Though duration of disease was considered as a variable, the researchers did not present these data in the latter study.

Medication
Two studies did not mention whether the participants were analyzed in an ON or OFF state [30,40,43].Three studies did not detail medication use [30,39,43].The use of dopaminergic medications (levodopa and/or dopamine agonist) was defined as the inclusion criterion for only one study [44].
Different professionals were involved in the facilitation of PA in the respective studies, and as such, the nature of the PA varied accordingly.Several professionals were involved in delivering and facilitating PA as an intervention, such as physiotherapists, personal trainers, dance teachers and yoga teachers/instructors.
In terms of non-motor symptom assessment, the studies identified utilized various instruments, with only one study using the Non-Motor Symptoms Questionnaire (N-MSQ) [42].The non-motor symptom assessments are further summarized in Table 4, and one of the fourteen studies did not evaluate any NMS [35].In addition, part I of the UPDRS was used to assess the non-motor aspects of experiences of daily living in only one study [37].
Analysis of the type of intervention performed in the studies showed significant benefits in the QoL scores for yoga practice [35,46] and the Mindfulness Mediation-Based Complex Exercise Program (MMBCEP) [30].Another study that applied PWT as a different form of exercise also had a positive impact on QoL [36].The study by Son et al. (2018) included stretching and complex strength exercises [30].As such, it could also be compared to the PA intervention performed in the previous study [36].The frequency and duration varied among studies.
Two studies measured PA with the 31-item Longitudinal Aging Study Amsterdam Physical Activity Questionnaire (LAPAQ) [34,44], whilst one study each used the International Physical Activity Questionnaire (IPAQ) [33] and the Physical Activity Scale for the Elderly [42], respectively.
In terms of activities of daily living and QoL, meaningful results were shown in two studies that utilized differing instruments, namely the Activities of Daily Living scale, the Schwab and England Activities of Daily Living Scale and MDS-UPDRS-ADL part II [40,41].In addition, falls were evaluated in two studies via questionnaires and considered as complications that can compromise motor function [33,44].Adherence to PA may be perceived as challenging for individuals affected by neurodegenerative diseases such as PD, whereby the symptom burden increases with disease progression [47].The barriers to initiating and maintaining regular exercise routines are multifaceted, including (1) body structure and function, of which PD motor and non-motor symptoms are part, (2) activities and participation, (3) personal and (4) environmental.Factors such as advancing age, comorbidities and frailty, alongside varying responses to treatment, can impede adherence to PA regimes.The detriment of reduced PA and a lack of mobility are postulated to accelerate frailty, fall risks, immobility and reduced QoL.When combined, a lack of PA may contribute towards an increased risk of hospitalization and the need for long-term care.
This complex interplay between physical activity and health outcomes necessitates a robust method for evaluating its effect on QoL, whereby the latter is considered a broad concept that encompasses biopsychosocial and spiritual well-being and should not be solely considered an absence of disease [48].In assessing QoL, homogeneity was observed across studies that utilized the PDQ-39.
Enhancements in QoL across different PA modalities that comprise individual and group forms of intervention, as well as facility-and home-based programs, highlight the potential of tailored physical activities to mitigate the barriers to implementation with the intention of improving overall health outcomes.In this review, we found one study that involved individual exercise programs at designated facilities and home-based regimes had yielded positive results in the outcomes measured, which included improvements in daily living activities and social support [36].

Motor Symptom Benefit
Physical therapy and specialized exercise programs have shown significant benefits in PD.A sensorimotor agility boot camp, involving activities like Tai Chi, boxing, lunges, kayaking, agility courses and Pilates, notably improved gait measures [33].Irish dance, although not initially sought after by individuals with PD, presents itself as a strategy that can improve mobility, thereby contributing to an enhanced quality of life [41].Additionally, it is an activity that can also be enjoyable and performed together with other family members.Conversely, the control group, engaging in a physiotherapy program, reported less benefits.
Resistance exercises and power resistance training (PWT) were particularly effective, showing more significant improvements in mobility [40,42] and muscle strength [30,36], as well as upper and lower limb bradykinesia [36].Furthermore, high-intensity exercise programs in non-demented individuals with mild to moderate stage PD may prove to be beneficial in terms of mobility and balance, thus facilitating the maintenance of independence and functional well-being [40].Moreover, improvements were also noted in areas related to endurance, coordination, agility, and balance [30,40], which further supports the role of varied and targeted exercise regimens in the management of PD.
Benefits related to dance therapy were seen in gains in the "Timed Up and Go test" and reductions in the Freezing of Gait Questionnaire scores given that rapid movements and step routines that are crucial for minimizing motor symptoms and enhancing balance and flexibility, potentially increasing the independence of individuals [41].

Non-Motor Symptom Benefits
It has been postulated that individuals in the early stages of PD, particularly those who retain cognitive abilities, may derive more significant benefits from PA.This advantage is likely due to the dependency of such activities on executive functions, which include attention and processing speed [49].
The effectiveness of home exercise programs was thought to be notably influenced by effect modifiers such as depression and cognitive impairment; importantly, age did not contribute significantly to the study findings [50].A study that compared a high-intensity multimodal exercise boot camp with the usual care found that the former significantly enhanced intrinsic motivation [33].Additionally, adherence to regular physical activity not only reduced fatigue [47] but also provided broader neurological health benefits, thereby improving overall quality of life [39].
Incorporating mindfulness meditation into complex exercise routines demonstrated substantial benefits.These activities enhance cognitive function and emotional well-being, which is thought to be highly relevant in the context of non-motor symptoms [45].The effectiveness of combining mindfulness-based stress reduction practices with PA, particularly in managing non-motor symptoms such as depression and anxiety, has also been evaluated positively [30,46].This combined approach has led to reduced anxiety and improvements in concentration, memory and performance in ADLs.

Benefits of Integrative and Synergistic Therapy
While traditional PA has long been validated within therapeutic contexts, emerging evidence underscores the efficacy of integrative therapies such as meditation and yoga.Studieshave demonstrated substantial improvements in depressive symptoms, mindfulness and cognitive performance among participants engaged in these practices [45,46].Additionally, these modalities have been shown to enhance psychospiritual outcomes, which directly mitigate symptoms of depression and anxiety [30,45].
Furthermore, the impact of such therapies extends to motor function improvements.Son et al. 2018 observed significant enhancements in physical performance measures, including the chair stand test, shoulder flexibility and walking tests such as the Six-Minute Walk Test [30].Meditation has been associated with increased joint flexibility, a decrease in resting tremor and general improvements in motor muscle function [30,34].These improvements are crucial, as they directly enhance performance in daily activities and the quality of life of both participants and their carers.
A significant decrease in bradykinesia scores and stiffness in both the upper and lower limbs following yoga interventions again suggests that an integrative and synergistic approach to physical activity interventions in PD may help maximize its therapeutic benefits [35].

Potential Therapeutic Mechanisms
An increase in BDNF following PA has been relatively well investigated by numerous studies that suggest its role in epigenetic processes that contribute towards synaptic neuroplasticity [51][52][53].Furthermore, exercise and its effects on cardiovascular-related microRNAs are likely to result in broader beneficial neurovascular effects which may con-tribute towards neuronal health [54,55].The expression levels of specific microRNAs have also been described in PD-specific studies that demonstrated exercise was associated with an improvement in cognition [56].The neurophysiological effects of exercise are further elucidated by studies that support changes in and the modulation of neural networks and oscillations, as reflected by functional neuroimaging (such as the upregulation of resting state networks) and electroencephalography, thus highlighting the state of local and interregional neural synchrony as crucial to appreciate in relation to an individual's function in the setting of neurodegenerative diseases such as PD [57][58][59].In addition, growing interest of the glymphatic system in PD and its beneficial modulatory effects on protein clearance and cerebrovascular indicators further strengthens the far-reaching effects of PA on brain health [60][61][62][63].

Limitations
The articles identified in this review indicate various forms of PA may be beneficial; however, comparison between the studies is challenging due to the differences in the PA interventions and overall study heterogeneity.Studies of this nature are often subject to a proportion of selection and participation bias, as well as potential Hawthorne effects.Another challenge perceived by the researchers was the performance of PA in "non-exercisers", which may be subject to the latter factors.

Conclusions
Despite differences in the study interventions and constructs, studies to date on the effects of PA on PD suggest tangible benefits in terms of both motor symptoms and NMS.Although a consensus recommendation on the best form of exercise as an intervention in PD is not currently available, it is likely that PA will be beneficial with a risk of minimal harm if patients are selected appropriately and the intervention is conducted in a safe environment.The positive impact of PA on QoL may be more significant in individuals who are able to consistently adhere and engage.Individualized PA interventions may provide better outcomes and are likely required with disease progression.Further research on PA is required to determine the best forms of therapy in people with PD and across the spectrum of its symptom burden.This would be further supported by studies that indicate the positive association of PA and neural function with the strong potential of this therapeutic modality to be better translated to and applied in the management of PD.

Figure 1 .
Figure 1.PRISMA 2020 systematic review flowchart of the selection of studies.

Figure 1 .
Figure 1.PRISMA 2020 systematic review flowchart of the selection of studies.
Abbreviations: 2MWT: 2-Minute Walk Test; 6MWT: 6-Minute Walk Test; AE: supervised aerobic exercise; AIG: aerobic intervention group; BBS: Berg Balance Scale; BD: Brazilian dance; BDI: Beck Depression Inventory; CS-PFP: Continuous-Scale Physical Functional Performance Test; DWE: deep-water exercise; EG: experimental group; FBF: supervised flexibility/balance/function exercise; FES-I: Falls Efficacy Scale-International; FFABQ: Fear of Falling Avoidance Behavior Questionnaire; FG: freeweight and elastic band group; FOG: Freezing of Gait Questionnaire; FRT: Functional Reach Test; FSS: Fatigue Severity Scale; GDS: Geriatric Depression Scale; GG: gym group; HADS: Hospital Anxiety and Depression Scale; HIAP: high intensity agility program; HIBC: high-intensity multimodal exercise boot camp; HY: Hatha yoga; ID: Irish dance; IPAQ: Physical Activity Questionnaire; MBEST: Mini-Balance Evaluation Systems Test; MDS-UPDRS: revised Movement Disorder Society Unified Parkinson's Disease Rating Scale; MMBCEP: Mindfulness Meditation-Based Complex Exercise Program; MMSE: Mini Mental State Examination; MoCA: Montreal Cognitive Assessment; NA: not available; NMSQ: Parkinson's Disease Non-Motor Symptom Questionnaire; NW: Nordic walking; PDSS: Parkinson's Disease Sleep Scale; PFS: Parkinson Fatigue Scale; PWT: power-based resistance training; SCOPA: Scales for Outcomes in Parkinson's Disease; STAI: State-Trait Anxiety Inventory; STS: Sit-to-Stand Test; TAPF: Test of Attentional Performance Flexibility; TMT: Trail Making Test; TUG: Timed Up and Go; TUG-FS: Timed Up and Go (fast speed); TUG-SSS: Timed Up and Go (self-selected speed); UPDRS I: Unified Parkinson's Disease Rating Scale part I (non-motor experiences of daily living); UPDRS II: Unified Parkinson's Disease Rating Scale part II (motor experiences of daily living); UPDRS III: Unified Parkinson's Disease Rating Scale part III (motor examination); UPDRS IV: Unified Parkinson's Disease Rating Scale part III (motor complications); UPDRS Total: Unified Parkinson's Disease Rating Scale total score, M-EDL: motor experiences of daily living.* The p-value was only present in the baseline results.+ p-value not reported, Confidence Interval/Effect Size suggestive of positive results

1 .
Physical Activity in Parkinson's Disease and Its Impact in Quality of Life

Table 1 .
Cohort demographics, including intervention and control groups.

Table 2 .
Interventions and methods of identified studies.

Table 3 .
Effects of physical activities on quality of life and functional well-being.

Table 4 .
Effects of physical activities on motor and non-motor symptoms.