Exercise for People with Parkinson’s Disease: Updates and Future Considerations

Abstract Parkinson’s disease (PD) is now the world’s fastest-growing neurological disorder with rapidly rising prevalence and increasing demand for effective health services. Recent research has focused on the importance of early diagnosis and proactive management of physical function. Accumulating evidence indicates that reduced physical activity levels and mild pre-clinical disability are present in many people prior to a clinical diagnosis, perhaps developing over years. Early referral to a physiotherapist at the time of diagnosis is now recommended in global guidelines. Multiple forms of exercise have been found to have benefits in early and mid-stage disease across a range of motor and non-motor symptoms. Evidence from longitudinal studies confirms that disability is delayed when regular exercise is sustained over long periods. Exercise is now recognized as an essential component of treatment, in combination with medical therapies. Contemporary physiotherapy interventions now combine health behavior change techniques with physical exercise to promote the development of long-term exercise adherence. Advances in technology and digital health have progressed quickly and now offer opportunities for remote assessment and monitoring, remote exercise supervision, and support adherence through feedback and motivational strategies. Recent biomedical discoveries forecast improved earlier and more accurate diagnosis of PD, allowing opportunities for earlier interventions. Current research in progress will provide important insights into the dose and intensity of aerobic exercise in PD. Physiotherapists have important roles in advocacy and education in conjunction with care delivery to support access to evidence-based care for all people with PD.


Introduction
Parkinson's disease (PD) is a common progressive neurological disease thought to affect around 9 million people by 2030 1) .The World Health Organization recognizes PD as the fastest-growing neurological disorder in terms of disability, hence health policy and healthcare planning must consider the increasing burden on healthcare systems 1) .Estimates of the number of people with PD in Japan vary, ranging from 0.136 2) to 0.26 million 3) .The social and economic burden is substantial and increases with disease progression, with annual care costs per person estimated to be 225,929 JPY in early disease and 250,025 JPY in advanced disease 4) .As the population in Japan continues to age, with an increasing prevalence of age-related neurological conditions, effective management of people with PD is of key importance.Although treatments for PD continue to develop, there is no cure, and symptom management across the lifespan is essential.Progression is inevitable, although the rate of deterioration varies considerably and many people live long lives with PD, even decades 5) .Physiotherapy plays a key role in multidisciplinary teams as an adjunct to medical interventions, enabling people to maintain their optimum function and quality of life.
Characterized by the loss of dopamine-producing cells in the basal ganglia, PD causes both motor and non-motor symptoms that affect a person's ability to perform activities in everyday life and restrict engagement and participation in social and community life.Common motor features include movement slowness, tremors, rigidity, postural instability, and difficulty with balance and gait 5) .Walking is often slow with small steps and freezing of gait is associated with an increased risk of falls 6) .Non-motor symptoms have been less well recognized but are equally common and include fatigue, sleep disturbance, mood changes including depression or anxiety, cognitive impairment, and autonomic dysfunction 5) .Both motor and non-motor symptoms vary in presence and severity and may fluctuate with medication cycles (on/off phenomenon).Recent accumulating evidence also indicates that women experience PD differently from men, with lesser motor progression and a different profile of non-motor symptoms including greater mood and sleep disturbances, fatigue, and pain 7) .This complex interaction of symptoms leads to increasing difficulty with activities of daily living including mobility, communication, social interaction, and employment.Motor progression is typically characterized by Hoehn and Yahr staging (see Table 1), representing progression from unilateral disease to bilateral, with trunk and balance involvement and increasing difficulty with walking, progressing to non-ambulant status in advanced disease 8) .The complex combination of both motor and non-motor symptoms in PD underscores the importance of physiotherapy to address the diverse needs of individuals living with this chronic condition.
Physiotherapists are recognized as experts in exercise and physical activity interventions.This paper aims to provide an overview of recent evidence from this field and highlights new areas of interest and future opportunities.

Exercise for People with PD is Recommended to Address Motor and Non-Motor Symptoms
The World Health Organization, National Institute of Clinical Evidence (UK), and other guideline authors now emphasize the need for access to expert integrated Confinement to bed or wheelchair unless aided From Goetz et al. 8) multidisciplinary services for people living with PD 1,[9][10][11][12] . A International and Multidisciplinary Rehabilitation Medicine Task Force recently developed a comprehensive consensus statement regarding multidisciplinary rehabilitation in PD care 9) .Optimal physiotherapy was considered important across all stages of the disease, from diagnosis to advanced PD. Physiotherapy-specific guidelines are now emerging, including those from Europe and the United States 11,13) .Medical rehabilitation guidelines in Japan support the key role of physiotherapy for the management of PD as a member of a multidisciplinary team, recognizing exercise as effective and safe 14) .Motor rehabilitation is recognized as effective in improving physical function, quality of life, gait speed, and fall risk reduction 15) .Detailed physiotherapy-specific guidelines from the Japanese Physical Therapy Association also recommend exercise from diagnosis onwards, providing specific recommendations across stages including a range of exercise modalities, acknowledging the variable strength of evidence and knowledge gaps 16) .
Positive evidence to support the benefits of physiotherapy and exercise in the routine care of people with PD has increased over the last decade, in both volume and quality.Progress has been rapid; the first Cochrane Review of Physiotherapy for people with PD in 2013 included only 39 randomized controlled trials (RCT), with only 8 trials identified as low risk of bias 17) .A recent Cochrane review of physical exercise in 2023 identified 154 RCTs, with generally higher quality methodology, supporting the beneficial effects of many types of exercise on a range of motor outcomes and quality of life 18) .The effective modalities that positively influence motor outcomes include (but are not restricted to) dance, aqua therapy, gait/balance/functional programs, mind-body, strength/resistance, and endurance programs 18) .The effective modalities that positively influence the quality of life include (but are not restricted to) aqua therapy, endurance activity, mind-body, gait/balance/functional programs, and strength exercises 18) .Importantly, the interventions were considered relatively safe, with no adverse effects 18) .The volume of evidence from recent meta-analyses addressing specific symptoms or functional difficulties is growing rapidly, confirming exercise as effective in improving freezing of gait 19) , hand dexterity 20) , and falls 21) , a significant burden for many people with PD.
As the body of evidence has grown, systematic reviews with meta-analyses have sought to compare the relative benefits of different types of exercise modalities and to understand whether certain forms of exercise are superior or best.As the contributing studies are usually heterogeneous across participants, intervention dose, and duration, with relatively few direct evaluations, network meta-analyses (NMA) provide the most evidence through the evaluation of direct and indirect effects.Broadly, these results confirm relatively small differences between exercise types and confirm that multiple modalities are effective 18,22,23) .As the methodology varies across reviews and exercise modalities are classified into different types, the results differ substantially across studies.One large NMA has examined specific modalities in greater detail, finding, for example, positive benefits from power training for motor symptoms and body weight supported treadmill training on balance and gait speed and distance 23) .The consolidation of positive findings from systematic reviews that address many symptoms is encouraging; however, caution is needed to interpret the evidence carefully and apply it to individual patients due to the large variation in the effect sizes and strength of evidence, treatment modalities, and outcomes assessed.Physiotherapists must consider the person's presenting symptoms, their goals, the presence of any comorbid health conditions, access, and preferences, and identify relevant evidence to support shared decision-making conversations in treatment decisions 24) .
As awareness of the significant burden of non-motor symptoms has increased over the last decade, attention has further focused on the potential effect of exercise and regular physical activity on these symptoms.It is also now recognized that some non-motor symptoms may present as barriers to regular exercise, such as apathy, depression, fatigue, or cognitive impairment.A systematic review evaluating the associations between physical inactivity and sedentary behavior confirmed that higher sedentary time is associated with worse cognition, with longitudinal cohort studies also suggesting low activity levels were associated with more depression and impaired cognition 25) .This highlights the importance of physiotherapists understanding and assessing both the motor and non-motor symptoms of PD and considering the impact on exercise adherence and treatment choices.
Systematic reviews are now exploring the effect of physical exercise on non-motor symptoms.A recent large umbrella review including 20 reviews of physical activity or exercise interventions confirmed that exergame, dance, resistance exercise, aerobic exercise, and combined interventions promoted improved cognition, although the optimal dose and duration remain uncertain 26) .This effect on cognition was confirmed in a separate review 27) , with a further suggestion that the effect was primarily on executive function, rather than other aspects of cognition.A smaller review focused on people with early to mid-stage PD (Hoehn and Yahr (H&Y) mean <2.5) found low-quality evidence that tango and mixed treadmill training improved non-motor symptoms, assessed using the MDS-UPDRS Part 1 22) .Exercise has also been found in meta-analyses to have a moderate to large effect on depression and a smaller on anxiety 28) .

Early Intervention: Diagnosis and Early-Stage Physiotherapy
The appropriate timing of rehabilitation interventions for people with PD has received considerable attention over recent years.Traditionally, referral to physiotherapy and other disciplines was considered appropriate when disability emerged, or symptoms interfered with function.The expectation was that therapy would provide compensatory approaches to adapt to inevitable motor decline rather than directly seek improvement in function through motor learning, skill acquisition, and exercise or seek to actively delay disability progression.In parallel, there has been increasing recognition that a PD diagnosis typically occurs after many years of preclinical disease progression and that preclinical changes in function may have already occurred.For example, around 25% of people with very mild disease (UPDRS < 20; median H&Y < 2) reported changes in walking, including slowness or greater difficulty 29) .A detailed review of subtle motor deficits prior to diagnosis included changes in gait patterns, balance, facial movement, and finger tapping, emerging between 2 and 10 years prior to clinical diagnosis 30) .
Contemporary recommendations now indicate that referral to physiotherapy or exercise health professionals is recommended at the time of diagnosis.This aligns with the adoption of an early and active 'secondary prevention' model, rather than a delayed rehabilitation program 31) .Late referrals, therefore, represent a "lost opportunity" to introduce pro-active and preventative measures in early disease to reduce worsening of disability or inactivity 31) .Early referral may provide opportunities for education regarding the benefits of sufficient regular physical activity and provide direction to community-based exercise programs.Baseline assessment using standardized measures and person-centered goal-oriented measures allows for regular monitoring over time, addressing motor function, fall risk, and home or community exercise programs in the early stages of PD 9) .As almost one in four people with PD are typically diagnosed while working age (< 65 years) 5) , particular attention to motor and non-motor demands of the person's occupational role is warranted.Knowledge from the field of occupational health should be used in conjunction with PD-specific evidence to ensure that people remain employed for as long as they choose and if possible.A recent large survey from the European Parkinson's Disease Association across 28 European countries examined the impact of employment on PD 32) .Symptoms that contributed to individuals leaving employment included fatigue, mobility, manual dexterity, sleep, and other non-motor symptoms 32) .Less than one in four people had received early intervention to manage their condition and considered this may have helped them remain at work.This study, in conjunction with others, suggests that physiotherapy may have a key role in supporting employment in people with PD who are working at the time of diagnosis.
Notably, around the time of PD diagnosis, a decline in daily activity and reports of increased difficulty with walking are common.A review of incident (newly diagnosed) cohorts with PD confirms that many people have lower physical activity levels than their peers.When diagnosed, the ICICLE cohort was around one-third less than peers without PD, taking fewer daily steps, and walking for fewer long (>2 minutes) bouts 33) .Similarly, loss of postural control may emerge earlier in PD than previously thought.In a group of newly diagnosed individuals with PD, around one in four had falls prior to diagnosis, and around one in three then fell within 18 months of diagnosis 34) .Given the evidence revealing the prevalence of inactivity early in the course of PD and the known benefits of exercise, it seems early initiation of physiotherapy has the potential to have the most impact 35) .
Isolating the effect of exercise on people at diagnosis or in very early disease is challenging, as most studies have included heterogeneous populations.Recent studies have focused on the efficacy of interventions for people with early disease, such as those who are de novo and taking no medication.A small RCT of inpatient multidisciplinary intensive rehabilitation treatments (MIRT) of 3 hours daily, 5 days a week for 4 weeks evaluated patients across 2 years.Compared to a control (no MIRT) group, the MIRT group had better motor scores, activities of daily living (ADL) scores, timed up and go, and lesser disability, indicating lesser disability progression 36) .Similarly, the SPARX RCT recruited de novo participants to participate in a trial of high and low-intensity treadmill exercise relative to usual care, finding that the higher-intensity program was feasible and had positive changes in the UDPRS motor scores, relative to the control group 37) .Participants with low initial step counts (<4200 daily steps) in the high-intensity treadmill exercise group also showed a large significant increase in daily step count and minutes of moderate-to-vigorous physical activity 38) .

Sustaining Long-Term Exercise Habits Over Long Periods: Health Behavior Change Support is Needed
Current frameworks suggest that people with PD should maintain or commence regular exercise from diagnosis onwards and develop lifelong exercise habits.Most of the evidence from RCTs has however evaluated only shortterm benefits and trials extending beyond 2 years are rare.Given that PD progresses slowly over many years, useful insights into longer-term benefits can be gained from cohort studies.
Li and colleagues 39) followed a cohort of 143 people with PD who trained in Tai Chi twice weekly over 4+ years.Compared to a control group, the Tai Chi group progressed less slowly annually (UPDRS total score), had smaller medication increases, maintained better mobility and balance, and had fewer complications 39) .Similar findings were evident in a large cohort of 237 people with early PD in Japan, followed over 5 years 40) .Higher physical activity levels over time were associated with a slower decline in postural and gait stability, ADL, and processing speed 40) .Similar findings were suggested in a single cohort of 55 people with PD who exercised over 5 years; annual progression of disease (1.7%) was considered lower than typical changes in general PD samples 41) .Collectively, these studies support the ongoing benefits of sustained regular exercise for people with PD over extended periods.Other studies also indicate the benefit of commencing regular exercise after previously being inactive; a 30-minute increase in exercise per week was associated with small positive changes in health-related quality of life and mobility 42) .
Sustaining enough exercise at regular intervals over long periods can be challenging.Like other chronic conditions, research has begun to focus on the self-management skills of people with PD, seeking factors that support longterm lifestyle modification including habitual exercise behavior.Multiple studies have now identified factors that may be modifiable and hence potentially useful in physiotherapy programs.Ellis et al. 43) used the International Classification of Functioning and Disability framework to explore exercise behavior determinants in a group of 260 people with PD categorized as regular exercisers or non-exercisers.Exercise self-efficacy was found to be a key factor; people with high exercise self-efficacy were twice as likely to exercise than those with lower self-efficacy 43) .Exercise self-efficacy was defined as "a person's belief in his or her capabilities to overcome personal, social, and environmental barriers to exercising" 43) .Older age and higher education were also significant factors associated with exercise.Higher disease severity was associated with exercise in initial univariate analysis but did not remain significant in multivariate analysis.Importantly, this study highlighted that the disabling influences of impairments and activity and participation limitations and restrictions were not associated with exercise behavior 43) .Further factors associated as negative influencers of exercise have included low-outcome expectations, lack of time, fear of falling, poor perceived health, bad weather, and lack of an exercise partner 44,45) .Notably, enjoyment of exercise was identified as a positive predictor of exercise 45) .
The presence of carer support has been identified as a potential facilitator of regular exercise behavior.A recent study evaluated the habitual physical activity of newly diagnosed people with PD with carers over an 18-month period 46) .Although activity levels did not change over time, carer psychosocial factors were associated with the physical activity levels of their PD partner; lower levels of carer anxiety and depression were associated with higher activity volume, and worse carer self-care was associated with a greater loss of physical activity volume 46) .This suggests that physiotherapists could consider including carers within interventions to improve physical activity and support and further consider the emotional well-being of the dyadic unit 46) .
Recognition of the challenge of long-term exercise adherence and identification of personal factors associated with exercise has led to the integration of health behavior change methods in physiotherapy interventions to increase exercise volume and adherence.For example, the large ParkFIT RCT integrated a behavior change program as an adjunct to an exercise program, including an activity coach who used strategies including education, barrier identification, goal setting and contracts, and feedback on activity levels 47) .Other studies have used peer coaches, virtual coaches, and mobile health apps for monitoring and telephone support or telehealth [48][49][50][51][52] . Te theoretical frameworks underpinning these interventions have varied across trials, including social cognitive theory, Bandura's self-efficacy theory, self-determination theory, the health belief model, and the trans-theoretical (stages of change) model among others 53) .Most interventions have been multi-component and there is no clear evidence that one specific behavioral approach is better than another 53) .Contemporary guidelines now recognize the importance of integrating health behavior change methods into interventions to increase or sustain exercise over the lifespan.Many trials are now also focused on home and community-based exercises, such as walking or stationary cycles, which address barriers such as access, transport, and time restrictions and facilitate recruitment of more diverse participant cohorts 54) .

Advances in Technology and Digital Health
Rapid changes to the capability, cost, and availability of technology in healthcare have provided opportunities for physiotherapy care for people with PD.Technology can support multiple aspects of care, enhancing assessment, as an integrated component of physical or behavior change interventions, and for remote monitoring of physical activity or exercise performance to provide patient feedback or tailored remote exercise progression.
Wearable sensors worn in daily life and during home exercise programs allow important insights into "real-world data."Sensors worn on the lower back over a week by 587 people with PD found the data to be moderately associated with clinical measures, and sensitive to early disease stage and disease progression 55) .Sensors integrated into commercially available devices such as the Parkinson's Kinetigraph (PKG TM ) are now used in neurologist-led care, to evaluate patients and optimize medication 56) .As PD typically includes movement variations and fluctuations within and across days, these insights are particularly important.Data such as these provide insights into on and off times and dyskinesia and may thus also allow physiotherapists to provide personalized education to identify optimum times for exercise and community activity and to consider periods of elevated fall risk.Such sensors are now being evaluated as a key component of the new home-based healthcare pathway model in the UK which combines supported self-management, remote monitoring, and self-directed access to healthcare contacts if needed 57) .Early results suggest that the model is acceptable, feasible, and safe and may be useful for remote or underserved communities 57) .
Sensors in body-worn devices have also been used in conjunction with specialized health software to provide opportunities to personalize exercise reminders, deliver encouragement, and feedback through messages, and tailor exercise progression remotely 51) .They do however have limitations including uncertain accuracy, cost, access to the sensors, hardware placement issues, and ease of data retrieval and interpretation.The effect of custom sensors to increase the physical activity of people with PD appears promising, yet requires further exploration 58) .
As an alternative to wearable sensors, existing integrated sensors within smartphones also offer opportunities for remote assessment, due to the widespread uptake of smartphones globally and the everyday habits of carrying phones.Various studies have explored data collected in everyday activity and in defined movement protocols to be used in home testing.The large mPower study captured data over 6 months from over 12,000 individuals (1414 with PD) who completed defined motor tasks or activities up to three times daily: finger tapping, speaking, walking, balance, and memory 59) .Performance in the motor tasks in a small subset of 21 people with PD found a reasonable correlation with objective clinical measures of disease severity (UPDRS_ MDS total score) 59) .
The wide consumer access to smartphones also offers new opportunities to develop and evaluate interventions that may be able to be implemented in remote areas or larger populations where healthcare services are limited.The STEPWISE RCT (in progress 60) ) aims to increase physical activity in people with PD, using a remote app (STEP-WISE); integrating motivational elements (virtual coach, positive text messages, personalized feedback about step count targets) and remote step count monitoring.The app is automated, thus testing the feasibility of an intervention that does not require human supervision.Remote assessment via smartphone offers exciting opportunities for personalized monitoring in routine physiotherapy practice yet will require careful consideration of the accuracy and the limitations of interpretation, and the acceptability of digital interventions to the person.
The development of augmented and virtual reality systems (AR and VR) has also provided new opportunities to address motor impairments, such as in gait or balance training.Virtual reality technology simulates the real world or similar environments, enabling a user to interact with a 2D or 3D environment using movement.It may be immersive (e.g., wearable headset) or non-immersive (computer screen or game console interface) and may include custom-developed or commercially available games ("exergaming").A key advantage of VR is the ability to provide a safer physical environment while allowing the person to attempt challenging movement tasks.
Virtual reality as a component of physiotherapy for PD has been evaluated using both customized programs developed for research and commercially available systems.Furthermore, the use of such systems provided attractive opportunities during the COVID-19 pandemic.A recent systematic review confirmed the efficacy of VR in improving balance and balance confidence, with no significant change in gait, ADL, or quality of life 61) .VR may also provide opportunities to combine aerobic exercise with a dual task or exergaming component.For example, the V-TIME trial added VR to treadmill exercise, requiring participants to navigate a simulated obstacle course with cognitive challenges, with real-time visual feedback of walking 55) .The VR-enhanced treadmill intervention was more effective in reducing fall risk than a treadmill without a VR.Individual studies have varied widely, with marked diversity across the types and demands of VR, the supervision required, and the dose.This confirms the potential advantages but indicates that additional knowledge is needed to identify the optimal dose and protocol, degree of challenge, and longer-term effects 61) .Commercially available systems offer obvious advantages in terms of access, cost, and availability, and emerging evidence suggests promising findings.A recent review of the effect of Nintendi Wii TM and Xbox Kinect TM on gait in PD suggested that both systems showed positive effects, with a small NMA providing limited support for Wii as a potentially superior device to influence gait 62) .

Future Directions: Improved Diagnostic Certainty and the Potential of Exercise as Neuroprotection
Emerging biological data are now also driving efforts to better define the diagnosis of PD and classification of phenotypes and staging, which is important for prognostic and therapeutic studies.Currently, the diagnosis is primarily clinical with limited accuracy and occurs late in the disease process, with around 60% of dopaminergic nigrostriatal neurons lost prior to diagnosis 63) .Diagnostic errors are common, with around 20% of people misdiagnosed at initial assessment 64) .The recent discovery of a new biomarker (α-synuclein seed amplification assays) in the well-characterized Parkinson's Progression Markers Initiative Cohort is anticipated to lead to biomarker-defined-at-risk cohorts and improve diagnostic certainty of PD for participants in new therapeutic trials 65) .In addition, the potential for wearable sensor data to support the inclusion of movement data to identify PD prior to clinical diagnosis is also emerging.Using the UK BioBank data, researchers used machine learning models trained using accelerometry data to distinguish between people with clinically diagnosed PD, Prodromal-PD, and healthy controls up to 7 years pre-diagnosis 66) .Over the next decade, research trials will likely benefit from improved definitions, which will amplify efforts in disease modification trials, including those including exercise.
The use of biomarkers to improve understanding of the effect of exercise and physical activity on disease progression in people with early PD has also expanded over the last 5 years.Extending from rodent models of PD that indicate neuroprotective effects on dopaminergic neurons, exercise studies are now integrating measures of brain-derived neurotrophic factor (BDNF) and imaging as outcome measures.A recent systematic review evaluated the effect of exercise on outcomes related to PD disease progression, finding limited low-certainty evidence showing improvement in "off" UPDRS scores and BDNF concentration 39) .
Although exercise and physical activity are now universally recommended for PD, much uncertainty remains as to the appropriate mode, frequency, and intensity that is necessary.Multiple exercise forms provide benefits and experts suggest multifaceted programs including elements such as aerobic, strengthening, motor-cognitive challenges (such as agility/balance/dual task, etc.), and flexibility.Aerobic exercise and the targeted intensity of exercise are particularly interesting in the studies exploring potential neuroprotective effects.Positive findings of the recent SPARX2 study 37) and Park-in-Shape trial 67) , which both included aerobic exercise at moderate-high intensity, provide strong support for recommendations that people with PD engage in aerobic exercise 3×/week, 30-to 40-minute main exercise set, 60%-80% of heart rate reserve or 70%-85% of heart rate max 68) .In lieu of heart rate, individuals can achieve an intensity of 14-17 on a 20-point rated perceived exertion (RPE) scale 68) .Current trials in progress that are nearing completion will provide a greater understanding of the appropriate dose for early PD (H&Y 1-III).These include the SPARX3 trial 69) (NCT04284436) which will evaluate 18 months of moderate and high-intensity endurance exercise for people within 3 years of diagnosis who are de-novo.Similarly, the CYCLE-II study (NCT04000360) evaluates a home-based high-intensity aerobic program on a stationary cycle over 12 months 54) .
Two recent key studies have provided important and exciting insights into the neural mechanisms underlying the positive effect of aerobic exercise on motor symptom progression 70,71) .De Laat and colleagues evaluated 10 people with mild disease (H&Y = 2, mean disease duration of 2 years) who engaged in high-intensity exercise over 6 months and found an improved or stable motor function 70) .Notably, positron emitting tomography imaging of dopamine transporter availability in the striatum and substantia nigra found a significant increase, rather than the expected decrease.Neuromelanin sensitive MRI identified similar changes in neuromelanin concentration in the substantia nigra; an increase rather than a decrease 35) .Similarly, a small study comparing functional and structural magnetic resonance imaging from people in the Park-in-Shape trial found enhanced functional connectivity in the right frontoparietal network and reduced global brain atrophy in those engaged in aerobic exercise, but not in the stretching group 71) .Together, these studies suggest aerobic exercise improves functionality in the remaining dopaminergic neurons and alters brain structure and function 70,71) .
The association between physical activity and PD is also now increasingly recognized in epidemiological studies examining the risk of developing PD.A very large systematic review including more than half a million participants found that physical activity was associated with a significant reduction in risk of PD 72) .Higher levels of physical activity and exercise were associated with a lower risk of PD, but notably, this occurred only in men.Related to the physical activity-PD risk focus, new research directions are considering the potential for regular exercise as part of a multicomponent lifestyle PD program 73) .An overview of current trials in progress that address physical activity in PD highlights seven RCTs expected to be completed over the next 2 years 74) .All of these RCTs focus on strategies to increase the overall volume of physical activity in everyday life, all are home-based, and all include a remote intervention component 74) .Knowledge from these trials should provide important information about adherence to regular exercise as part of lifestyle change.
The phases of PD development and progression are also the focus of considerable research interest.A prodromal phase (prodromal-PD) of 10-15 years prior to clinical diagnosis has been identified, characterized by non-motor symptoms including hyposmia, constipation, REM sleep behavior disorder, and mood disorders 5) .A first-of-its-kind trial (Slow-SPEED-NL NCT06193252) has just commenced, to assess the possible efficacy of an exercise intervention to increase exercise volume in a group of people with prodromal PD 75) .This will have important implications for physiotherapy but also highlight opportunities for physiotherapists to engage further in exercise research in PD.

Conclusion
Research over the last decade has strengthened the evidence for physiotherapy support of people with PD; expert neurologists now regard exercise as critical in symptom management 73) .Further important questions remain; the intensity and optimal dose-response require further clarification, and strategies to best support long-term adherence, such as exergaming or remote coaching need further exploration.Further studies with early-stage cohorts will provide insights into whether the effects on motor function are symptomatic (delay disability progression) or are related to disease modification 5) .Of equal importance, studies with people with mid-stage disease confirm the effectiveness of a range of modalities to delay the progression of hand, walking, and balance dysfunction, to reduce the risk of falling, and to support higher health-related quality of life.
The physiotherapy profession has an important challenge to support the goal that all people with PD can access evidence-based care as part of a multidisciplinary team across their lifespan.Expert skills in exercise prescription, and empowering chronic disease self-management are needed to tailor individual programs across the lifespan.Advocacy is needed to influence health policy to ensure equitable access and adequate funding.Education is needed at community and government levels to increase awareness of PD and the range of social supports needed.The engagement of physiotherapists in exercise-focused research is needed to ensure that the studies consider the implementation of the programs into the range of environments and contexts in which people with PD live.
Funding: Not applicable.

Conflicts of Interest:
The authors have no conflicts of interest to declare.