Parkinson’s disease (PD) is the second largest neurodegenerative disease after Alzheimer’s disease at present. It is estimated will affect about 17 million people in the world by 2040 (Dorsey et al., 2018). In addition to the typical motor symptoms such as static tremor, rigidity, and bradykinesia, non-motor symptoms (NMS) such as sleep disorders, cognitive decline, anxiety, and depression are also commonly seen and have a negative impact on patients’ quality of life in PD.

Activities of daily living (ADL) refers to the necessary activities that a person performs every day to meet the needs of daily life. It includes basic skills such as dressing, bathing, eating, and other complex activities like social communication, which is closely related to the quality of life. In the PD population, disease severity seriously affects ADL. With the progress of PD, ADL ability decreases (Hariz and Forsgren, 2011; Bouça-Machado et al., 2022).

Studies have also shown that PD patients with poorer sleep quality and cognition usually have a lower ability to life (Thorpe et al., 2016; Çavuşoğlu et al., 2021). PD itself may interact with sleep, and patients with sleep disorders always have the more progressive aggravation of neurodegenerative processes (Ju et al., 2014; Schütz et al., 2022) which seriously reduces the patient’s quality of life (Thorpe et al., 2016). Sleep alterations also occur before the motor alterations in PD. Rapid eye movement (REM) behavior disorder (RBD) is a potential prodromal biomarker to PD, it is reported RBD can cause alpha-synuclein deposition and neuroinflammation, and accelerating the progression of PD, besides, circadian rhythm injury can also contribute to abnormal inflammatory reaction under the pathogenesis of PD, glymphatic system dysfunction plays a pathogenic role in it (Scott-Massey et al., 2022). Sleep disorder greatly increased risk of PD.

Cognitive impairment can be seen at an early stage in PD. Any types of cognitive impairment are closely related to the severity of PD measured by the Hoehn-Yahr (H-Y) stage and can lead to the deterioration of neuropsychology and quality of life (Simon-Gozalbo et al., 2020). It was proposed that cognitive deficits can affect the awareness of ADL, resulting in the impairment of ADL capability (Hartle et al., 2022).

In view of the effect of disease severity, sleep quality, and cognitive function on ADL and clinical manifestations in PD patients, we have no doubt that in PD patients, disease severity, sleep quality, and cognitive function all have an impact on ADL. But how disease severity, sleep quality, and cognitive function overall affect ADL is still unclear.

After searching the relevant literature, we did not find any research about the synthetical influence of sleep quality, disease severity, and cognition on the ADL of PD. However, a better understanding of how they interact is very important and will help us to improve the ADL of patients, especially the early PD patients, and eventually to improve the quality of life in PD patients.

Therefore, the aim of this study was to explore the interrelationships between sleep quality, disease severity, cognition, and ADL in PD patients. We hypothesized that in the population of PD, sleep quality and disease severity are associated with ADL, and assumed the mediating process is regulated by cognition (Figure 1).

In this study, we tested a model of interactions between sleep quality, disease severity, and ADL in PD patients. This study revealed that cognition played a role of moderator which confirmed our hypothesis. Sleep quality directly affected ADL and indirectly affected ADL via disease severity, furthermore, cognition moderated the association between sleep quality and ADL, and the indirect effect gradually decreased as a score of MMSE increased, indicating that better cognition played the role in moderating and palliating between sleep quality and ADL. In other words, patients with poor sleep quality affect ADL by aggravating the severity of the disease, and better cognition plays a role in buffering these negative effects.

The evaluation of sleep disorders is increasingly recognized as an important aspect of the health of patients with chronic diseases. Firstly, consistent with recent studies, our results indicated that poor sleep quality could be a risk factor for decreased ADL ability in PD patients (Liguori et al., 2021; Yi et al., 2022). Sleep quality can affect ADL in multiple ways, Arias-Fernández et al. (2021) found poor sleep quality was associated with impaired physical function and were linked to muscle weakness in older adults. Rolinski et al. (2014) found PD patients with RBD related to a higher prevalence of mood disorders and a greater impact on ADL. Poor sleepers usually displayed greater anxiety and also fatigue, serotonin is thought to be a major factor in this occurrence. Besides, in an early PD cohort, clear association had been found between poor sleep quality and worsening depression over time, so it still needs to be explored further to determine if these symptoms play important roles in the path sleep quality affect ADL (Koh et al., 2022). PD patients with sleep disorders often experienced more NMS than those without sleep disorders (Neikrug et al., 2014), it has been demonstrated that poor sleep can also aggravate pain and cognitive impairment, while these NMS are important determinant factors of the quality of life in PD patients (Rana et al., 2018; Santos García et al., 2021). So, we considered sleep quality as an important factor which affects ADL. In addition to motor symptoms, the overall consideration of the impact of non-motor symptoms, including sleep disturbance and cognition, on quality of life is worthy of future research.

Secondly, we found poor sleep quality was associated with more severe PD stages. The connection between sleep and neurodegenerative disorders has been highlighted in many studies (Valdinocci et al., 2017; Scott-Massey et al., 2022; Kopeć et al., 2023; Wang et al., 2023). Mechanisms behind sleep quality influencing disease severity in neurodegenerative diseases remain speculative: Accumulation of neurotoxic proteins, including α-synuclein (α-syn) in PD and amyloid β-protein (Aβ) and tau in Alzheimer’s disease (AD), is a common pathological mechanism. In AD, poor sleep may increase neuronal activity, and decrease the clearance efficiency of extracellular metabolites, which may contribute to Aβ and tau accumulation (Minakawa, 2022). As for α-syn, research in mice and humans proved that persistent wakefulness due to impaired sleep can raise the extracellular soluble α-syn in the interstitial fluid (ISF) and cerebrospinal fluid (CSF) (Holth et al., 2019) and accelerates PD progression. Glymphatic system dysfunction plays a pathogenic role in it. The main function of the glymphatic system is to facilitate the removal of pathological proteins and metabolites to optimize neurological functions, it was reported bidirectional relationships exist between α-syn, glymphatic system and sleep (Scott-Massey et al., 2022). Sleep disruption impairs the glymphatic system and may lead to future abnormal α-syn aggregation, and α-syn accumulation further causes the suppressed glymphatic clearance, then, the impaired glymphatic clearance further aggravates α-syn deposition and PD pathology (Zhang et al., 2023). Moreover, the interplay between sleep and neuroinflammatory reaction and nigral-dopaminergic neuronal system degeneration may also aggravate motor impairment (Lauretti et al., 2017; Zou et al., 2019; Ding et al., 2021), thus affect disease severity in PD. In our model, we pointed out that disease severity plays an indispensable part in mediating the association between sleep quality and ADL, but it only mediates this relationship to a limited extent. This suggests clinical practice or future research should explore additional mediators in order to offer a more comprehensive view of the complex link between sleep quality and ADL.

Finally, our study showed that cognition played a moderating role in the relationship between ADL and PD severity. Cognition deficit is one of the major clinical non-motor symptoms of PD, about 40% of PD patients at an earlier stage have mild cognitive impairment (MCI), and approximately 40% of PD-MCI progress to Parkinson’s disease dementia (PDD) over 3 years (Aarsland and Kurz, 2010; Weintraub et al., 2018). Cognitive deficits were proved to be related to ADL difficulties in PD population (Rosenthal et al., 2010). Basic ADL, instrumental activities, and advanced activities are three items stratified by ADL. Previous studies showed the appearance of cognitive dysfunction usually impairs advanced activities at first and then affects basic activities with the decline of cognitive ability (De Vriendt et al., 2012). Besides, cognition deficit is also associated with severity of PD, patients with PD-MCI and PDD always present a higher score of H-Y scale, as well as a worse motor and functional levels, which aggravates the decline of ADL capability (Happe et al., 2002; Lysen et al., 2019; Simon-Gozalbo et al., 2020; Yi et al., 2022). These studies suggested that early prevention and intervention of cognitive deficits are necessary to keep ADL capability.

A recent study showed that cognition decline can mediate the impact of sleep quality on the H-Y stage in PD patients, and was considered to be caused by impairment of the nigrostriatal dopaminergic system (Pfeiffer, 2016; Yi et al., 2022). However, in our study, we put cognition as a moderator, not a mediator, and did not find its moderating effect between sleep quality and the H-Y stage, which may indicate that cognition plays a role of a mediator not a moderator in the relationship between sleep quality and the H-Y stage.

Our findings have theoretical and practical implications for improving ADL in PD patients. In theory, the model explains the correlation mechanism behind sleep quality, disease severity, ADL, and cognition, and lays a foundation for the next step of research. In practice, the results are instructive for improving ADL in PD, intervention for sleep and cognition decline may be an appropriate choice to alleviate ADL decline.

There are several limitations to our study. First, data analysis showed that the mean MMSE score was 24.43 ± 5.06, median H-Y stage was 2 (1.5–3.0), which indicates that most patients have the good cognitive ability and are in the early stage of PD disease. It is difficult to enroll patients of H-Y stage 4–5 due to their limited cognitive and behavioral abilities, so our conclusion may more appropriate for PD patients in an early stage. Second, PSQI has relatively low sensitivity and specificity as a self-report questionnaire, it is necessary to evaluate the sleep quality of patients from the perspective of caregivers. Sometimes the patient said he had a good night, but the caregivers clearly know he had a bad night, which is common in the outpatient clinic. Further studies using more objective methods, such as polysomnography, are needed to investigate the relationship between sleep and ADL. Third, data were cross-sectional and acquired from only one center, the cross-sectional data made making causal inferences between the identified variables and ADL challenging, further longitudinal studies and sample size expansion need to be performed to investigate the causal link between sleep quality and ADL. Finally, we did not have information on variables including depression, anxiety, apathy, all of which could affect ADL, so there may be residual confounding factors that we have not controlled for, additional research is required to identify other potential mechanisms, so as to improve our model.

Despite the limitations above, our study tested and expanded an intervention perspective model of sleep quality, ADL, disease severity and cognition, indicated a close relationship between ADL and sleep and cognition in PD, and also provided new insights into the overall management of PD and a better quality of life of PD patients.

The original contributions presented in the study are included in the article, further inquiries can be directed to the corresponding authors.

This study was approved by the ethics committee of the Second Affiliated Hospital of Soochow University (JD-LK-2021-132-02) and informed consent was obtained from all participants.

YL and CM conceived and designed the study. YL, JL, and DC collected the data, analyzed the data, and drafted the manuscript. ML, YY, JH, JW, and FW collected the data. CM, CL, and JC critically revised it. All authors contributed to the interpretations of the findings and reviewed the manuscript.