In the early-stage PD, patients’ postural abnormalities are mainly characterized by forward or lateral trunk flexion during standing, and head and neck flexion (33, 34), when functional deficits are relatively minor significant milestone indicating the progression of the disease is the onset of freezing gait. A study of the kinetics of the turning process in 23 PD patients revealed that individuals with PD turn more slowly and require more steps to complete the turning maneuver (35). Mortality tends to rise when patients develop postural and gait symptoms——mainly due to falls, hip fractures, etc. Typically, an individual with PD experiences a seven-year decrease in life expectancy after they start to fall (36). The pathophysiologic causes and determinants of freezing gait are multifaceted. Fasano et al. (37) found that the site of the lesion leading to freezing gait is functionally connected to a focal area in the dorsomedial cerebellum; Lewis et al. (38) proposed that there are different pathophysiologic circuits in the brain and that alterations or damage to individual circuits can imbalance the entire neural network, ultimately leading to the development of a freezing gait.

PD patients may exhibit excessive muscle activity in the muscles governing their knee joint (39). Patients can improve their gait with most forms of physical activity (6). Exercise in a body weight-supported environment promotes normalized activation of the extensor muscles of the lower extremities in PD patients, and extensor off-activation time and peak muscle activation will normalize when weight support approaches 80% (39). PD patients may see a reduction in over-activation of their extensor muscles in a low-gravity environment which can help patients with their postural irregularities and efficiently manage the tone of their lower limb muscles. PD patients benefit from treadmill training which improves their gait and walking ability, including stride length and walking speed (40, 41). A result of a randomized controlled study showed that 8 weeks of treadmill training significantly improved gait and postural stability in PD patients. Rose et al. (42) reported that PD patients had a 10.6% increase in mean walking distance after 8 weeks of aerobic exercise on anti-gravity treadmill. Baizabal-Carvallo et al. (43) investigated the effects of 4 weeks of anti-gravity treadmill training in PD patients with moderate-to-severe gait freezing, revealing increased gait speed and stride length. 84% of the patients reported moderate or significant improvement in gait, indicating potential benefits of the anti-gravity treadmill even in PD patients with low MoCA scores (i.e., cognitive deficits are present). The pathophysiology of freezing gait is intricate, and the neurophysiologic mechanisms by which anti-gravity treadmills improve freezing gait are not yet fully comprehended. However, some researchers have hypothesized that under low-gravity conditions, decreased ground reaction forces and reduced proprioceptive inputs may lead to better integration of neuronal motor circuits with certain motor abilities in PD patients and that patients may also be able to enhance neuronal compensatory mechanisms by improving their gait (43), which may lead to an improvement in freezing gait. PD patients who are older may find it difficult to run or increase their walking speed without fear of falling when using the traditional treadmill. Steadily raising their weight on the anti-gravity treadmill until they can support their entire body weight, enables them to practice exercises and gradually boost their self-confidence in their athletic ability.

Physical activity is defined as any bodily movement caused by skeletal muscles that results in energy expenditure (44). According to studies, those who engage in regular, prolonged, moderate-to-intense physical activity have a 40% lower chance of acquiring PD than people who lead sedentary lives (45). Muscle weakness and other motor deficits significantly hinder the ability of people with PD to participate in physical activities, resulting in significantly lower levels of physical activity (46). PD patients who fall frequently also have trouble performing daily tasks and have a strong dread of falling again (47). If balance deficits and fear of falling persist or worsen, this may prevent PD patients from performing activities of daily living. Matinolli et al. (48) indicated that increased disease severity and postural sway seem to be the most important independent risk factors for the occurrence of falls in PD patients. A recent survey of falls in PD patients showed that falls were twice as frequent as in age-matched older adults (49).

In PD-affected mice, exercise has been demonstrated to boost dopamine receptor DA-D2R (50), and comparable outcomes have been seen in PD patients (51). Research has shown that after 4 weeks of anti-gravity training, the Test of Timed Up and Go (TUG) was shortened by 7 s in PD patients (43), which significantly improved the dynamic balance and reduced the risk of falls. In the sagittal and cross-sectional planes, PD patients demonstrated increased performance in executing dynamic balance-related tasks after 8 weeks of anti-gravity treadmill training, as evidenced by a 24% improvement in the completion time of the five sit-to-stand tests (52). However, this study had a small sample size and only male PD patients. Further studies are required to investigate the effects of an anti-gravity treadmill on dynamic balance and physical activity in PD patients in a larger sample size.

One of the most common non-motor symptoms of PD is cognitive dysfunction; at the time of diagnosis, 20%–33% of individuals had modest cognitive impairment (53). Research has demonstrated a significant correlation between motor and motor learning deficits and cognitive dysfunction in PD patients (54, 55). Nevertheless, bradykinesia is a risk factor for mild cognitive impairment in PD patients and this population is at higher risk for cognitive impairment (56). Patients with early PD had significantly lower serum BDNF levels compared to healthy controls (57). However, experimental animal studies have shown that the treadmill exercise increased the levels of BDNF and GDNF in the striatum of a rat model of PD (58, 59), upregulated the levels of Nrf2 and γGCLC, and reversed dopaminergic neurodegeneration of the substantial nigrastrata (60). They exert neurorestorative and neuroprotective effects by modulating neurotrophic factors to stimulate synapse formation and angiogenesis, inhibit oxidative stress, and improve mitochondrial function. Johansson et al. (61) demonstrated that aerobic exercise reduces brain atrophy, stabilizes motor processes, and enhances cognitive performance in PD patients by stimulating functional and structural plasticity in cortical striatal sensorimotor and cognitive control networks, while Fisher et al. (51) showed that exercise increases the neuroplasticity of dopaminergic signaling. A review noted that in PD patients, strength, flexibility, motor control, and cognitive abilities are consistently improved by exercise, resulting in better functional abilities (62). These findings are consistent with those of PD animal models.

Besides providing similar benefits to aerobic training on a conventional treadmill, the anti-gravity treadmill is also more applicable to elderly, less mobile, and mid-to-late-stage PD patients. However, there are still gaps in research on exercise therapy to improve cognitive deficits in patients with PD, and more large-sample, multicenter, randomized controlled studies need to be included in the future to guide a more diverse range of rehabilitative treatments for PD patients.

The motor and non-motor symptoms of PD significantly impact the quality of life, including physical, mental, emotional, social, and economic aspects. A meta-analysis revealed that PD patients scored poorer on most measures of quality of life than healthy controls, particularly in terms of their physical and mental well-being (54). Numerous studies have shown that depression is the most significant factor affecting quality of life (63, 64), accounting for 60% of the quality of life impairment (65). Anxiety, apathy, and pain are also associated with quality of life in PD patients (66) and have a greater impact than motor symptoms. Patient’s reduced quality of life not only hurts their treatment plan but also shortens their life expectancy (67).

Anti-gravity treadmill training can improve the quality of life and negative emotions in PD patients. Research reveals that after 8 weeks of anti-gravity treadmill exercise, PD patients experienced a significant improvement in their PDQ-39 index, with an average increase of 8.3 points in the composite index, representing a 32.6% improvement compared to healthy controls (42). Atan et al. (68) found significant improvements in energy and physical activity subgroup scores on the Nottingham Health Profile (NHP) after a 6-week weight support training program for PD patients. Animal experiments demonstrated that treadmill exercise prevented depressive-like behavior and restored the levels of proBDNF, BDNF, and TrkB in the striatum and hippocampus of mice with PD, suggesting the effectiveness of exercise training in neuroprotection of the striatum and hippocampus (69). However, there is considerable variation in the scales currently used in different studies investigating quality of life, depression, and anxiety in PD patients. For example, several research measures like the Hamilton Depression Rating Scale (HDRS) and the Beck Depression Inventory (BDI) used for assessing depression in PD patients have not received approval for use within this patient population (70). To assure high-quality study data and enable comparability among related studies, we strongly advise researchers to use officially recommended or suggested scales in their future research, as well as provide details about the statistical procedures used.

Given the distress caused by motor and non-motor symptoms in PD patients, along with the prevalence of anxiety, depression, and adverse reactions to medications, they are susceptible to sleep disorders, which can negatively affect the regression of the disease. Sleep represents the most common non-motor symptom of PD, with a prevalence of approximately 47.66%–89.10% (71). Research indicates that both physical activity levels and ideal sleep patterns are independently associated with a lower risk of PD, whereas individuals with high physical activity levels and ideal sleep patterns have the lowest risk of developing PD. Therefore, enhancing physical activity levels and sleep quality may be promising targets for intervention to prevent PD (72). A study noted that treadmill training increased cortical striatal neuroplasticity and dopamine release, thereby improving sleep quality (73). Treadmill training represents the most straightforward type of aerobic exercise, and the anti-gravity treadmill, amalgamating the benefits of the traditional treadmill and is more practical and safer in PD, can be effective in improving physical activity levels and sleep disorders in PD patients, thereby improving their quality of life. However, other studies with larger sample sizes and higher quality are needed to validate the effects of the anti-gravity treadmill on the quality of life of PD patients.