Introduction

Parkinson's disease (PD) affects 6 million people worldwide [1], making it one of the most common neurological syndromes derived from dopamine loss. Resting tremor, bradykinesia, rigidity, postural instability, and gait impairment are the main cardinal symptoms. Besides them, the psychological and emotional spheres are often involved, increasing disease severity [2]. While such diverse factors as aging, free radical toxicity, mitochondrial dysfunction, genetics, and environmental stressors can trigger PD onset [3], its etiology remains unknown.

Given the wide range of symptoms and inter-individual differences, a personalized and multidisciplinary approach to appropriate treatment planning is warranted. Currently, levodopa (L-DOPA) administration in the early PD stages is the gold standard therapy. Unfortunately, its chronic use induces dyskinesias accompanied by worsening of general health [4]. However, there is evidence from both human and animal models [5, 6] that, owing to its neuroprotective role [7], exercise can improve motor impairment and physical condition in PD patients regardless of the stage of the disease. To evaluate the most effective exercise-based treatments, patients are required to undergo clinical tests to identify disease stage-specific vital and motor parameters.

Currently, clear recommendations for the most suitable clinical exercise tests are lacking. Studies describe numerous tests that evaluate the domains affected by PD [38, 71], but the necessity to prescribe the correct exercise depending on the outcome of each test is still underestimated. Likewise, little is known about exercise programs in terms of frequency, intensity, time, and type (FITT) of intervention addressed to PD patients based on disease severity. High-intensity exercise and long-term therapy have been associated with greater benefits than low-intensity and medium- or short-term therapies [6, 8]. Moreover, a combination of mobility exercise, gait, and balance training [9], occupational therapy, cued exercises, high-intensity aerobic and resistance activities are recommended [10]. The effectiveness of training different muscle groups through various activities is increasingly recognized, along with the importance of supervision and motivation during preferred training activities. However, the most effective training program for PD patients remains a matter of debate.

Additionally, it is important to couple exercise and medication to maximize the beneficial effects over time and potentially counteract long-term drug side effects. While exercise training can be added to medications to manage disease symptoms and enhance their benefits [72], more rigorous investigations have to be conducted for cognitive function, daily living activities (ADL), and psychosocial variables. Even though exercise does not change greatly medications’ effects, PD patients respond better during the “on” phase, or when they can move fluently thanks to the still circulating drug rather than during the “off” phase, when symptoms tend to reappear with compromised movements.

The present study aimed to review the PD literature on exercise testing, on personalized training programs and the impact of exercise on antiparkinsonian drug-treatment. The findings are summarized as indications for exercise-based non-pharmacological approaches to manage PD symptoms in each stage of the Hoehn and Yahr (H&Y) classification [11].

Methods

Following the PRISMA guidelines for systematic review of the literature [12], controlled clinical trials, systematic reviews, and works containing guidelines were identified and included by means of a computerized literature search in the Google Scholar, MEDLINE, Pubmed, and Cochrane Library electronic databases with the following keywords: Parkinson’s disease AND physical therapy, training AND Parkinson, exercise, exercise AND drug. Furthermore, references and cross-references, bibliographies, citations of articles or publications were reviewed. The search strategy focused on (1) articles in English published from 1986 to 2019, (2) patients with PD and the respective exercise-based non-pharmacological prescribed treatment, (3) disease stage (H&Y classification), clinical tests, exercise prescription, type, intensity, and frequency of training, and drug administration. Selection criteria for clinical tests and training protocols were feasibility, usefulness, safety of each approach, in addition to compliance of subjects, and improvements of deficits described in the included works. Retrieved articles were grouped as follows: exercise testing, training protocol prescription and interaction between exercise and medication. The first two sections were further classified into three core areas: endurance, strength, and flexibility.

After excluding non-relevant articles, a total of 50 records were included (Fig. 1).

Fig. 1
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Literature review flow chart: records retrieved, screened selected and included in the review

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Results

Exercise testing

To obtain maximal benefits, the prescription of a personalized program upon clinical evaluation, functional capacity, mental health, and general fitness (e.g., cardiorespiratory fitness, muscular strength and endurance, flexibility) is suggested [13]. Moreover, given the chronic and progressive nature of PD, reassessment every 6–12 months to review the diagnosis and test program is recommended [11]. Albeit just for a few PD-related deficits, the general clinical tools for PD diagnosis are the older and simpler H&Y scale [14] and the newer Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) [15]. However, in addition to scales and questionnaires, the most appropriate clinical test for examinations remain a matter of clinical judgment. Thus, the present review summarizes the most suitable exercise tests into the three main core areas of physical activity: endurance, strength, and flexibility.

Endurance assessment

Eleven articles were reviewed for endurance assessment. Generally, all studies included patients with mild-to-moderate disease (1–3 H&Y). Only one focused on advanced PD. Six researches tested patients under medication; in one study the patients were in off status, and four articles did not mention medication status. There was one randomized controlled trial, one research report, five clinical studies; the remaining two included reviews that validated the results. Additionally, a book and a research article which both contain two published guidelines were used. The endurance assessment tests are summarized in Table 1. Table 2 presents the specifics of each test.

Table 1 Endurance assessment tests
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Table 2 Summary of endurance assessment tests
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Balance assessment

Ten articles on balance, functional mobility, and postural instability testing were included as considered indexes that are helpful for a general evaluation of PD. One report tested patients with PD (H&Y stage 1–4) and provided a guideline that generally refers to each disease stage; the other studies did not specifically mention disease stage. Patients under medication were tested in four studies, in one the patients were in “off” status; in two they were “in-between”; six articles did not mention medication status. This rubric included one research report, three clinical studies; the remaining four were reviews that validated the results. Additionally, a book and a research article which both contain guidelines were used. Balance assessment tests are summarized in Table 3. Table 4 presents the specifics of each test.

Table 3 Balance assessment tests
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Table 4 Summary of balance assessment tests
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Resistance assessment

Nine studies evaluated measurement tools for assessing muscular strength; there was one research report and 6 clinical studies. The American College of Sports Medicine (ACSM) Guidelines for Exercise Testing and Prescription and the European Guidelines for Physiotherapy were examined for all disease stages. Six included PD patients with mild to moderate disease, generally in “on” status. Only one study involved older adults, without specifying the chronic conditions. All resistance assessment tests are summarized in Table 5. Table 6 presents the specifics for each test.

Table 5 Resistance assessment tests
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Table 6 Summary of resistance assessment test
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Flexibility assessment

One clinical study was reviewed for flexibility and range of motion (ROM) evaluation of mild to moderate disease. One book containing guidelines was used. Both works included PD patients in their “on” status. All flexibility assessment tests are summarized in Table 7. Table 8 presents the specifics of each test.

Table 7 Flexibility assessment tests
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Table 8 Summary of flexibility assessment tests
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Training protocol prescription

The beneficial effects of exercise programs are marked in both healthy aging and PD [16]. There is also a strong connection between FITT of regular exercise and physical function in PD. Unfortunately, the optimal exercise type and dose are yet to be identified. There is much uncertainty about whether exercise influences the risk of developing the disease [17]. A better understanding of the mechanisms underpinning the exercise effect is important, as it will lead to more targeted interventions for optimal physical activity.

Since the current literature is scarce, the ACSM Guidelines for Exercise Testing and Prescription recommend improving of four main factors: gait, transfer, balance, and functional capacity. Major issues are the level of physical exertion which a PD patient can be subjected to and the most effective non-pharmacological modality (e.g., physiotherapy, walking, running, strength training or functional exercises) that can be safely prescribed. Recently, complementary programs like dance and Tai Chi have been positively re-evaluated [18]; such challenging exercises train multiple aspects of physical status simultaneously. For example, they improve walking speed, direction changes, and muscle strength in balance and gait. Furthermore, aerobic training and the "random practice" have beneficial effects of task-switching capability, particularly for PD patients. It is essential to prescribe a variety of activities to overcome the difficulties of PD patients to change activities and perform two actions simultaneously. Random practice and variation of movements will help to improve this.

Clinicians can adapt exercises from the training programs for healthy adults; indeed, both healthy adults and early-stage PD patients may present similar improvements in their general fitness and functional capacity [19]. The only advice is to adapt exercises to each person, taking into account cardiorespiratory functions, physical limitations, mental health, and disease stage progression assessed during a previous medical visit [11]. Differently, in stage 4 PD, patients need modified exercises because of the severe limitations in balance and gait. Contrarily, in bedridden patients in stage 5, the program is restricted to a palliative approach to prevent deformities or rapid physical decline [20]. Figure 2 illustrates the main objectives at each stage of PD.

Fig. 2
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Main objectives at each PD stage

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Endurance training

In this section, 19 articles were included; the endurance training interventions are summarized in Table 4. The most recent papers were published in 2019, the oldest one dates from 2000. Seven studies were randomized controlled trials, six reviews, four works containing guidelines for PD management; among the remaining two, one was a clinical trial and the other a test–retest reliability study. All the studies reported benefits and improvements in PD patients after following a program of aerobic therapy that included a minimum of 20 min and a maximum of 60 min of activity. The outcome scores and main features of the studies are summarized in Table 9.

Table 9 Endurance training protocol
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Resistance training

Twelve studies were included; the resistance training interventions are summarized in Table 5. The most recent articles were published in 2019, the oldest one dates from 2003. Two were randomized controlled trials, six reviews, four works include guidelines for PD management; of the remaining two, one was a clinical trial and the other a test–retest reliability study. All the studies reported benefits and improvements in PD patients after following a program of resistance physical therapy (minimum of 1–4 sets and multiple repetitions) in those with mild-to-moderate disease. Results and specifics of the studies are summarized in Table 10.

Table 10 Resistance training protocol
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Flexibility training

None of the eight studies that analysed flexibility reported which is the best program for each H&Y stage. The studies included patients with early to moderate stage but none with more advanced stages. The most recent article was published in 2018 and the oldest in 2008. Three were randomized controlled trials, one was a review, four works contain guidelines for PD management. Only general recommendations about exercise frequency, time, and intensity were mentioned. Considering the exercise type, the patients were encouraged to follow a complete flexibility training program that mobilizes each body district, without distinction. The results and main features of the studies are summarized in Table 11.

Table 11 Flexibility training protocol
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Interaction between exercise and medication

Seven studies were reviewed that summarized current knowledge about the effects of physical exercise on drug absorption and efficacy in PD. Six specifically tested the effects of aerobic exercise on L-DOPA administration in PD patients with H&Y stage 1–3; no study tested patients with more advanced stage and no articles were found on drug response to resistance and flexibility exercises; only one exploited a MPTP-toxin parkinsonian mouse model used by two other studies about molecular mechanisms underlying the beneficial effects of physical exercise. One review article was added as support.

In three studies, patients exercised on a treadmill and on a cycle ergometer in four. As final assessment tools, blood samples were taken in three studies to monitor drug concentrations, UPDRS-III score was used in three, whereas only one trial reported physiological parameters (heart rate, blood pressure). The animal-based study also used behavioral testing, immunohistochemistry, and transcriptome analysis. Outcome scores and main features of the studies are summarized in Table 12.

Table 12 Interaction between exercise and medication
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Discussion

Endurance and balance assessment

There are valid strategies for performing endurance assessment; the choice will be dictated primarily by the focus of the study. During a clinical exercise test for endurance, also known as a fitness assessment, subjects are generally in their “on” status and are monitored while doing a battery of exercises at maximal or submaximal intensity depending on disease severity [21], graded workload exercises (GXT) on a treadmill or a stationary cycle ergometer until exhaustion [19, 22]. Likewise, patients can be tested with constant workload or free body exercise utilizing step tests. Aerobic fitness, an important parameter for most sports, can be severely impaired in illness, worsening the patient’s quality of life. The patient’s overall health and physical status can be evaluated to obtain the baseline measurements for programming a personalized exercise regimen.

Clinicians should exploit several different screening tools to determine baseline parameters [e.g., height, weight, resting heart rate (RHR), and resting blood pressure (RBP)] and compare them to the measurement taken during peak exercise or after the test. Another main objective of these tests is to measure cardiovascular performance, metabolic parameters (e.g., maximal oxygen uptake [VO2max], METs) via stress testing and monitor the cardiopulmonary response to oxygen supply, rate of perceived exertion (RPE) [23], and electrocardiogram (ECG) continuously monitored during activity. Moreover, test results may be helpful to determine functional problems, to predict the risk of falls [69], and to evaluate the effectiveness of an intervention [24]. Attention should be directed to testing balance, falling [25], and gait [26] using, for example, the Timed Up and Go (TUG), the Åstrand-Rhyming protocol during GXT, and the Berg Balance Scale (BBS), which are the most widely used evaluation tools [11, 27,28,29].

Common endurance tests, such as the 6-min walk test [27, 28] or the 2-min walk test [30] for patients with advanced PD [31], can be easily administered without special equipment and provide a complete framework of aerobic and gait capacities when coupled with GXT protocols. Because PD is a progressive disease, patients require repeated physical evaluations over time and adjustments to their training program according to disease stage [11], motor disabilities, and L-DOPA-induced complications, which may preclude safe adherence to an endurance exercise protocol (Tables 13–15). The following indications are recommended for all patients with PD (1–5 H&Y):

  • PD patients often suffer from cardiac dysrhythmias.

  • Exercise should start 45–60 min after medication has been taken.

  • Inquire about changes in medication.

  • Patients with significant fluctuation should be tested while in the “on” and the “off” status.

  • Individuals unable to perform a GXT (due to risk of falling, severe stooped posture, deconditioning) may require a radionuclide stress test or stress echocardiography.

  • Continuously monitor heart rate, blood pressure, ECG, RPE, and other signs.

  • Standard procedures, contraindications, recommended monitoring intervals, and standard termination criteria are used in exercise testing of individuals with PD.

  • For deconditioned patients with lower limb weakness, compromised balance or history of falling, precautions should be taken (gait belt, harness, and technician assistance), especially at the final stages of the test when fatigue occurs, and the individual’s walking may worsen.

  • Deep brain stimulation device, if present, should be deactivated to avoid interference with ECG recording. Remember that, without stimulation, the patient will be in a compromised mobile state and will not be able to achieve maximal tolerance (physical discomfort, tremor, cramping, and emotional symptoms).

Table 13 General Recommendations: clinical testing and training for Early PD diagnosis
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Resistance assessment

Muscle weakness is a primary symptom of PD, not only due to consequences of aging and inactivity. It is directly correlated with lesion of the basal ganglia that impedes activation of motor neurons and results in muscle weakness [32]. Strength can be tested by measuring the maximal amount of force a muscle group can exert at one time. The primary goal is to train and improve muscle strength by developing a personalized program after baseline assessment. The exercise tests are definite for each muscle group with instrumental measurements using tensiometers or dynamometers [33,34,35]. Upper body exercise tests include the Static Handgrip Strength Test [36], the Manual Muscle Test [11, 36, 37], and the Arm Curl Test [11, 37, 38], while for the lower body the Chair Rise Test [37] or the Five Time Sit to Stand Test [29] are recommended. Note that the One-Repetition Maximum (1-RM) test is not limited to only one exercise type and that it can be conducted in a wide variety of assessments [39] (Tables 13, 14, 15). The following indications are recommended for all patients with PD (1–5 H&Y):

  • The standard index for strength assessment is the 1-RM, which is determined after completing a series of submaximal repetitions of a specific exercise.

  • Resistance is initially within the patient’s perceived capacity (50–70% of capacity). Only when the series is completed correctly it can be progressively increased.

  • It may be necessary to use very light weights or substitute them with household items.

  • A metronome is a useful to measure how long the patient can keep up with the rhythm.

  • A warm-up phase of 5–10 min is always recommended.

  • Patients at risk for cardiovascular, pulmonary or metabolic diseases should perform adapted tests.

Table 14 General Recommendations: clinical testing and training for Moderate PD diagnosis
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Table 15 General recommendations: clinical testing and training for Advanced PD diagnosis
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Flexibility assessment

Flexibility refers to the ability to completely move a joint during sports and daily activities. Continuous training to exercise joints is important in injury prevention. At the early stages of the disease, patients often experience rigidity of limbs, neck or trunk, hip and shoulder, which leads to a reduced ROM, postural imbalance [10] and instability. Because of the increased resistance to movement, patients exhibit bradykinesia, muscle stiffness, pain, and cramps, fixed facial expression, difficulty turning over in bed or getting out of a chair and performing activities of daily living [29].

Since the entire body is often involved, diverse tests are administered to assess the level of flexibility and then tailor the best exercise battery to the patient’s needs.

Exploited devices in assessment include goniometers, electrogoniometers, tape measures, inclinometers, and Leighton flexometer [38]. While, for visual measurement of ROM, flexibility level can be estimated directly by screening the neck, trunk, hip, shoulder and postural motion observation through simple flexion, abduction, adduction, rotation, supination, pronation, and inversion recorded in degrees [11] (Tables 13, 14, 15). The following indications are recommended for all patients with PD (1–5 H&Y):

  • Have the patient warm-up before the evaluation and use adapted protocols as needed.

  • Show the patient how to perform the movement being evaluated.

  • Encourage the patient to stretch to the point of slight discomfort without pain.

  • Perform all tests during peak medication when the patient’s mobility is optimal.

Endurance training

Endurance exercise training refers to exercise that improves cardiorespiratory fitness, i.e., VO2max, and cardiorespiratory endurance that refers to how long an individual can perform an activity using large muscle groups. It has been suggested that PD patients can benefit from aerobic training and maintain high levels of physical function [40, 70] by performing high intensity exercises. Alternatively, leg cycle ergometry, arm ergometry or combined ergometry are valid strategies to record physical performance or cardiorespiratory fitness [41,42,43,44] in patients with severe limitations [11]. Exercise training may involve repetitive movements that guide and gradually activate the neuromuscular system by working on motor functions over time. Furthermore, good results can be obtained with a gradual aerobic exercise program for cardiovascular autonomic regulation by improving systolic blood pressure and response to orthostatic stress [19, 45]. Moreover, improvements in general fitness [20, 43, 46], fatigue, bradykinesia, gait [47,48,49], and ADL [50] are obtained after exercise at light-moderate intensity in patients with mild-to-moderate PD.

Animal studies have associated exercise dose (e.g., frequency, duration, intensity, and type of exercise) to neuroprotective effects [51]. Differently in humans, benefits of endurance exercise have been observed only in general motion, walking speed, balance improvement, and cortical reorganization favored by neuroplasticity events [52,53,54]. Furthermore, aerobic exercise has been proved to be effective for improving heart, lungs, metabolic, and circulatory systems by reducing the risk of chronic diseases such as diabetes, heart diseases, and stroke.

However, the evidence for optimal exercise dose treatment to improve function in PD remains unknown. While it is recognized that all approaches lead to positive effects, the choice of the protocol best tailored to each patient must, firstly, guarantee safety during execution. Clinicians need to consider the stage of the illness, drug-dependent status, and physical limitations, while encouraging engagement in light, moderate or vigorous exercise, according to maximum capability and motivation also in deconditioned PD patients (Tables 13, 14, 15).

Resistance training

In almost all PD patients, muscle strength declines most notably in the flexors and extensors of the hip, knee, wrist, hands, and core muscles [49]. This reduction compromises gait and general physical functions, increasing the risk of falls. Muscle weakness is a serious impairment that alters the individual’s ability to perform activities of daily living such as simply standing up from a chair or stepping. A valid approach is to prescribe specific training protocols that exercise major muscle groups, especially the lower limbs, without causing excessive fatigue [55,56,57]. Resistance training can comprise a variety of exercises, use of weight machines or bodyweight; generally, 2–3 days of weekly resistance exercise at moderate to high intensity with more than 1 set and multiple repetitions are recommended. Although the studies reviewed here focused on early and moderate stages (H&Y stage 1–3) of PD, the appropriate exercise type depends on the individual fitness, stage of illness and experience with physical activity (Tables 13–15).

Flexibility training

Rigidity is an obstacle to movement, especially when it affects lower limbs resulting in shorter steps and altered walking pace. All studies agree that regular stretching is essential in PD exercise programs. When performed multiple times per week or daily in adjunct with mobility and resistance exercises [15, 17], it may diminish muscle rigidity accompanying the illness [58]. Exercise also ameliorates muscles and joints flexibility and general health status [11, 53]. To facilitate routine movements, few tips are necessary to bring significant benefits, such as adapting both exercise and stretching time to comorbidities and PD limitations, not dynamic movements and avoiding pain. Information on the exact duration of stretching therapy is unknown. One study found a loss of efficacy 2 months after the end of the therapy and recommended continuation and repetition of flexibility training over time, especially near the peak effect of L-DOPA [59], to maintain benefits (Tables 13, 14, 15).

Interaction between exercise and medication

Physical activity in patients with PD shows improvements in motor symptoms, but, more importantly, also in non-motor signs, since exercise involves many different brain areas. Pharmacotherapy for motor signs is helpful but may worsen non-motor symptoms, especially in the long term, or accentuate compulsive disorders. The duration of "on" periods and drug effectiveness diminish with chronic L-DOPA usage, probably due to disease progression rather than the treatment itself [60]. However, treatment interruptions to avoid adverse effects can lead to regression of the disease. To date, no studies have evaluated the impact of physical activity without pharmacological support, given the ethical restrictions on standards of care. Nevertheless, important discoveries concern the positive effects of physical activity on drug-induced disorders, such as amantadine or L-DOPA, still considered the gold standard therapy. Although some studies did not report significant gaps in L-DOPA metabolism, a different outcome during cycling exercise and at rest indicated [61,62,63] three different responses, as exercise can either increase or decrease L-DOPA absorption or induce no significant change (H&Y stage 2–3).

In individuals with idiopathic PD (H&Y stage 1–2.5), the UPDRS motor score, together with blood sample analysis [64], during endurance exercise on a bike ergometer showed a slight improvement in motor response to L-DOPA administration when compared to resting condition under medication. Likely higher blood pressure and heart rate due to exercise contribute toward better drug transport over the blood–brain barrier and reduced drug storage in the periphery. More recently, these physiological parameters were studied together with the endocrine release of norepinephrine [65] during on and off medication status, at rest, and during a treadmill stress test. The results confirmed a lower autonomic response in the PD groups compared to the healthy controls. Indeed, while much work remains to be done, it was hypothesized that antiparkinsonian medication does not affect autonomic responses or motor outcomes; in contrast, abnormalities in heart rate or blood pressure are predominantly due to the disease. In a few conflicting cases [66] it was reported that L-DOPA and dopamine agonists may have had a negative effect on systolic blood pressure during a treadmill protocol, leading to limited cardiopulmonary responses to exercise in the PD patients under medication.

Physical and pharmacological therapies appear to act on the same molecular pathways but lead to opposite effects. Apparently both regulate dopamine and neuropeptides levels [52] but L-DOPA increases the release of neurotransmitters and interrupts the regular signaling between receptors and substrates, while physical exercise tends to rebalance dopamine levels and the body's homeostasis by mobilizing gene profiling and facilitating brain plasticity processes [67].

Other experiments conducted on MPTP-treated mice [68] identified three genes that normally regulate cell growth and neurogrowth factors, which in PD are activated by exercise and inhibited by drugs. Despite this general trend, the CREB1, RICTOR, and L-DOPA genes also respond slightly differently, depending on the cortical area in which they are expressed and on the disease stage. This difference may explain the diverse outcomes in patients during therapy and the choice to defer or limit drug dosage in those whose life quality is not seriously affected by PD. Although other data are needed to determine quantitatively and qualitatively how physical activity interacts with drugs, it is established that their combination is more beneficial than single treatment alone.

Limitations

This review has some limitations. Many of the studies were of short duration and involved a small sample of patients without a control group. Most had mild to moderate disease; few studies included patients at more advanced PD stages. Since PD is a chronic degenerative disorder, studies of longer duration and with larger populations are needed to confirm the results and to transform them into appropriate guidelines for patients with severe disease. Furthermore, future studies that clarify the sensitivity, and reliability of the assessments, as well as the compliance of patients with PD in joining different training programs are strongly needed, to improve the choice of appropriate clinical tests, protocols and the understanding of their outcomes.

Conclusions

For this review, we collected data from recently published studies that investigated physical training as a significant non-pharmacological treatment for neurodegeneration in PD. We aimed to find the most appropriate and suitable clinical tests for each disease stage and to identify the impairments to be treated with training according to each PD level. To date, there are no solutions to completely avoid drug prescription nor a standard exercise protocol to be broadly offered to patients. General modalities of exercise such as endurance training, resistance training, and flexibility training are increasingly recognized to alleviate symptoms in PD and thus improve quality of life; on the other hand, uncertainty and insufficient data remain about the interaction between exercise and drug delivery, especially for pharmacokinetics and pharmacodynamics.

A future area of focus is the correct FITT of exercise that can be personalized according to disease stage and drug dose. For now, it seems that the most effective training protocol is the one that combines multiple exercise modalities to be performed routinely during the week and in the long term, to maintain benefits on endurance, resistance, and flexibility (Tables 13, 14, 15). Hence, patients can manage symptoms and improve their general health. However, because PD is an irreversible and progressive disease, patients will require regular monitoring with specific clinical and exercise-test evaluations and adjustments to their training protocols and therapeutic plans based on symptom-related changes over time.