To date, few studies have investigated sarcopenia in patients with PD, especially within the Han population. This is the first study to report that sarcopenia is strongly and independently associated with symptoms of fatigue and severe disturbances in sleep quality in Han Chinese patients with PD. Our results also indicated that the incidence of sarcopenia was greatly higher in patients with PD than in the healthy controls, which is accordance with with the results reported in previous studies. Furthermore, our ROC analysis indicated that combined use of FSS and PSQI scores may be a valuable screening method for identifying sarcopenia in patients with PD.
Our analysis confirmed that the appearance of sarcopenia is significantly associated with the age of the patient, which is consistent with the definition of sarcopenia as a geriatric disease and published geriatric literature[22, 23]. Previous studies have demonstrated that older adults often experience a reduction in skeletal muscle mass, which is considered to be related to nervous system alterations and changes in metabolism, hormone levels, nutrition, and physical activity[23, 24]. These changes in muscle mass and function can lead to disability, reduced mobility, functional dependence, and functional decline[25–27]. Similarly, in our study, patients with PD who had sarcopenia exhibited poorer nutritional status and lower BMI than their counterparts without sarcopenia. From a clinical perspective, these results highlight the need to screen for sarcopenia in older adults with PD and address changes in nutritional status and BMI as early as possible in the treatment process.
Notably, although many patients with PD in our study were in the early stage of the disease, a loss of muscle mass was still observed in these patients. Furthermore, in accordance with the findings of Tamer et al., we observed significant decreases in muscle mass with disease progression. These decreases in muscle mass exert a negative impact on patient prognosis, emphasizing the importance of early detection and intervention.
The incidence of sarcopenia was also higher in our sample of patients with PD than in the general older adult population in China. This may be related to the existence of common pathophysiological pathways affected by PD and sarcopenia, including those associated with inflammation, autophagy, oxidative stress, and apoptosis[17, 30, 31]. Several studies have indicated that high levels of interleukin-6 (IL-6), are related to the loss of muscle mass and lower body function, as well as the incidence of older adults[32, 33]. Some studies have also reported that IL-6 levels and signalling pathways are imbalanced in patients with neurodegenerative diseases, and higher serum IL-6 levels have been associated with a slower gait in patients with PD. In addition, these patients exhibit extreme difficulty in maintaining balance. Therefore, increases in IL-6 levels may lead to weakness and fatigue in patients with PD, further contributing to functional decline.
Changes in brain structure and brain networks are thought to exert a great influence on the pathophysiology of sarcopenia in patients with PD. In their study of patients with PD, Wu et al. observed that decreased mass in core thigh muscles was associated with lower grey matter volumes in the left superior temporal gyrus and right hook gyrus, longer disease duration, and female sex. The reduction of network capacity in the default mode leads to insufficient activity of the task-related network during task execution, which leads to low motor function.
In addition, Drey et al. reported that the UPDRS-III score is significantly related to early sarcopenia, suggesting that there may be a common pathway in the preclinical stage of the two diseases, and that sarcopenia may be a sign of PD in the preclinical stage. Caviness further observed that, when compared with healthy controls, patients with PD exhibited significant decreases in the number of motor units in the hand muscles. Another study by Drey et al. indicated that the number of motor neurons is reduced in older adults with sarcopenia, suggesting that neurodegeneration plays a key role in the pathogenesis of sarcopenia.
Sarcopenia may also be affected by hormonal changes in patients with PD. Androgens play an important role in maintaining muscle mass, and low plasma testosterone levels may lead to the development or progression of sarcopenia. However, no studies have explored the relationship between testosterone levels and sarcopenia in patients with PD, necessitating further research for clarification. In addition, gastrointestinal infections and the use of levodopa may impact muscle mass in patients with PD. Further, the motor dysfunction associated with PD may lead to significant decreases in muscle mass and physical ability relative to levels observed in healthy older adults.
Our findings indicated that sarcopenia as determined based on BIA findings is negatively associated with sleep quality and the severity of fatigue in patients with PD. Sleep and fatigue are the two main NMS of PD. Further, the prevalence of sleep disorders in patients with PD is 47.7–89.1%, which is higher than that in the general population. Sleep disorders in patients with PD may be due to degeneration of thalamocortical pathways and alterations in neurotransmitter levels. While the exact mechanism underlying the link between sarcopenia and sleep disorders remains unclear, several potential explanations have been proposed. Recent research has indicated that sleep might exert an important influence on muscle protein metabolism. During aging, individuals experience decreases in the duration and quality of sleep as well as the circadian rhythm is disturbed, and the prevalence of sleep disorders is increasing. This situation favours proteolysis and may lead to changes in body composition that addition the hazard of insulin resistance. In addition, studies have suggested that levels of growth hormone (GH), insulin-like growth factor-1 (IGF-1), and testosterone play a role in the association between sarcopenia and sleep disorders. Decreased physical activity levels in patients with PD may represent another mechanism underlying the link between sarcopenia and sleep disorders. In this study, we did not evaluate the relationship between physical activity and endocrine hormone levels, and next research is required to explore whether mechanisms associated with these variables can explain the link between sleep disorders and sarcopenia in patients with PD. Treating sleep disorders, normalising circadian rhythms and sleep homeostasis, and maintaining good sleep quality may provide a tactics for maintaining or restoring muscle health in these patients.
Fatigue refers to the subjective experience of a lack of energy and physical exhaustion, which is common in patients with PD and can bring about the quality of life go down. Studies have also reported a close relevance between muscle mass and fatigue in patients with cancer, suggesting that decreases muscle mass may be a critical factor in the development of fatigue. We speculate that early evaluation and management of skeletal sarcopenia may better the quality of life of patients with PD by reducing symptoms of fatigue. Given that sleep and fatigue may be involved in the association between PD and sarcopenia, we attempted to determine whether FSS and PSQI scores had enough discriminative power to distinguish sarcopenia in patients with PD. ROC curve analysis revealed that the AUC values for the FSS and PSQI were 0.725 and 0.776, respectively, while that for combined use of the FSS and PSQI reached 0.804. These results indicate that FSS and PSQI scores exhibit acceptable sensitivity and specificity for the potential discrimination of sarcopenia in patients with PD.
The present study had some limitations. First, the study was executed at the PD Clinic in Suzhou, where eating habits and ethnicity are relatively homogenous. Therefore, our findings may not be applicable to other, more diverse populations, highlighting the need for multicentre studies to confirm our results. Second, by excluding patients who were unable to cooperate with the assessments and those in the late stages of PD who could not stand on their own, we may have underestimated the prevalence of sarcopenia, as these excluded patients may have had more severe features than included patients. In addition, we did not use objective tools for assessments of sleep. In future studies, polysomnography (PSG) can be used to better evaluate and analyse the relationship between sleep characteristics and sarcopenia in patients with PD. Finally, the cross-sectional nature of our study allows us to report only the association of sarcopenia with patient fatigue and sleep, but we cannot state the direction of this relationship. Long-term follow-up studies and cohort studies are required further explore these relationships.