Evaluation of Nocturnal Symptoms in Chinese Parkinson’s Disease Patients Based on the PDSS-2 Scale: A Multicenter Cross-Sectional Study

INTRODUCTION

Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide, which is caused by the progressive degeneration of the central nervous system, affecting motor and non-motor functions and resulting in disability [1]. In 2016, about 6.1 million people were diagnosed with PD, which was 2.4 times higher compared to 1990 [2]. In China, the prevalence rate of PD is 1.7% for people older than 65 years old, similar to that in European and American countries [3]. With the aging of the Chinese population, the number of Chinese PD patients will increase to 5 million in 2030 and might constitute almost half of all PD patients globally [4]. It is suggested that the characteristics of Chinese PD patients are the most representative in the world [4]. Besides, the burden of PD patients is not only associated with rising costs for medication or hospitalization and nursing home care but also a serious decrease in patients’ quality of life [4, 5]. Therefore, it is necessary to strengthen the understanding and management of PD patients in China.

In addition to common symptoms such as resting tremor, rigidity, bradykinesia, posture, and gait disorders, PD patients also suffer from sleep-related symptoms, such as insomnia, rapid eye movement sleep behavior disorder (RBD), excessive daytime sleepiness (EDS), restless legs syndrome (RLS), nighttime akinesia, and difficulties in getting up [6, 7]. The causes of nocturnal symptoms of PD included both the disease itself and the side effects of medications [8]. Nocturnal symptoms significantly affect the quality of life in PD patients [9], but they are often ignored or underestimated in clinical practice [10].

A large questionnaire-based survey in Germany showed that 84.4% of PD patients had a poor quality of life and symptoms, including early morning akinesia (55.4%) and sleep disorders (43.5%), which are common forms of nocturnal symptoms [11]. Studies in the UK [12] and Slovakia [13] demonstrated that 50% and 63% of PD patients showed nocturnal symptoms, respectively. Previous studies in Chinese PD patients [14–17] evaluated the nocturnal symptoms and quality of life and found that most of them had sleep problems. Similar results were also observed in the Japanese [10] population.

Nocturnal symptoms present a challenge for physicians to diagnose as they mainly appear at night and are frequently compensated by fatigue and EDS [9]. Hence, numerous scales have been used to evaluate the sleep-related symptoms of PD, such as the Epworth Sleepiness Scale (ESS) and Parkinson’s disease sleep scale (PDSS) [18–21]. PDSS-2 has been developed recently, which could better cover nocturnal symptoms not included previously (e.g., restless leg syndrome, nocturnal pain, akinesia, and sleep apnea) [22–24]. PDSS-2 score has already been utilized in studies to identify changes in sleep quality in PD patients and proved to be less methodology- and sample-dependent compared to other scores [25, 26].

This study aimed to explore the prevalence and associated factors of nocturnal symptoms in a large group of Chinese PD patients, as well as the relationship between nocturnal symptoms and quality of life. The study might help strengthen our understanding of the prevalence and impact of sleep-related symptoms in PD and perhaps help manage these symptoms.

METHODS

RESULTS

The scale score of nocturnal symptoms in Chinese PD patients

As shown in Fig. 1, the average PDSS-2 total score of all patients was 13.68, with a sleep disturbance score of 7.45, a night motor symptoms score of 3.56, and a nocturnal PD symptoms score of 2.67. The most complained item was “get up at night to pass urine” (average score: 2.46), followed by “difficulties in staying asleep” (average score: 1.56) and “bad sleep quality” (average score: 1.43).

OPEN IN VIEWER

Fig. 1

Evaluation of nocturnal symptoms in Chinese PD patients with or without nocturnal symptoms. A) The Parkinson’s disease sleep scale 2 (PDSS-2) score, sleep disturbance score, night motor symptoms score, and nocturnal PD symptoms score; B) the Parkinson’s disease questionnaire 8 (PDQ-8) score; C) the presence and severity of depression; D) the presence and severity of anxiety.

In the nocturnal symptoms group, the PDSS-2 total score was significantly higher than the non-nocturnal symptoms group (23.23±7.49 vs. 7.72±3.91). The scores of sleep disturbance, night movement symptom, and nocturnal PD symptom in both groups were 11.30±3.63 vs. 5.06±3.07, 6.67±3.94 vs. 1.61±1.68, and 5.26±3.39 vs. 1.05±1.44, respectively, indicating that the frequencies of other motor symptoms at night and other PD symptoms at night were approximately five times higher in patients with nocturnal symptoms.

In addition, the PDQ-8 total score was 32.64±18.35 points in patients with nocturnal symptoms compared with 14.31±14.97 in those without nocturnal symptoms (p < 0.01). Moderate and severe depression was reported more often (p < 0.01), and the occurrence and severity of anxiety were higher as well in the former compared to the latter group (p < 0.01).

DISCUSSION

Nocturnal symptoms are common in PD patients and might seriously affect the quality of their life [9, 12]. Due to the difficulties in health monitoring during nighttime, patients and doctors often ignore those symptoms, leading to persistence or worsening [28]. This study explored the occurrence of nocturnal symptoms and associated factors in a large group of Chinese patients with PD and the relationship between nocturnal symptoms and quality of life, aiming to strengthen doctors’ and patients’ understanding and draw attention to nocturnal symptoms of PD.

To our knowledge, this is the first national study to investigate the prevalence of nocturnal symptoms in outpatients diagnosed with PD in China. With a large sample size of 1500 cases, we reported that in the Chinese population, 38.4% of patients with early- and mid-stage PD were found to have nocturnal symptoms, of which 59.2% were older than 65 years. The most common symptoms were sleep disorders and factors related to the development of nocturnal symptoms included a lower education level, presence of advanced depression, longer disease duration, and a higher Hoehn-Yahr stage.

Bhidayasiri et al. [29] reported a high prevalence rate of nocturnal symptoms the Thai population (96.6% of all PD patients). In the present study, the prevalence of nocturnal symptoms in Chinese PD patients was as low as 38.4%. Several reasons may explain the inconsistent results, despite that both studies are among the Asian population. Firstly, the sample sizes of both studies were different, and the vast majority of the patients included in our study were at early and middle stages, which may lead to a lower prevalence of nocturnal symptoms. Secondly, the evaluation tools differed (the PDSS-2 scale in this study and the MPDSS scale in Bhidayasiri’s study). Thirdly, the present study set stricter diagnostic criteria for nocturnal symptoms. Suzuki et al. [10] showed that a total score of PDSS-2 ≥15 could help to detect lack of sleep in PD patients. Nevertheless, an MPDSS score ≤6 was considered abnormal in Bhidayasiri’s study. Studies in the Caucasian population evaluated nocturnal symptoms using Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale, and the prevalence rates were slightly higher than our results (50% in the UK [12] and 63% in Slovakia [13]).

Pandey et al. [12] assessed the quality of sleep by Pittsburgh Sleep Quality Index and EDS by Epworth Sleepiness Scale and reported nocturnal symptoms in 50% of patients (50/100). Poor sleep quality was not related to low quality of life in the abovementioned study, with authors hypothesizing it being the secondary outcome to reported depression and anxiety. In our study, multiple factors were found to be related to the quality of life among Chinese PD patients, including the presence of nocturnal symptoms (p < 0.001). Most likely, the difference could be explained by the different sample size, as previous studies also supported the association between sleep quality and quality of life [9].

On the other hand, Havlikova [13], using the same scales and almost the same number of patients (all of whom were Caucasians), reported various sleep-related problems during nighttime in 73.1%, but only 24.7% of patients had PSQI score >5, with no significant association between depression and lower quality of life. At the same time, the authors noted a question of appropriate evaluation for depression in the sample, as only patients who were able and motivated to come in for examination and interview were usually included in the studies.

Therefore, choosing the evaluation scale is essential for accurate assessment of nocturnal symptoms. PDSS-2 is a second revision of the visual analog scale PDSS addressing 15 commonly reported symptoms associated with sleep disturbance. The original PDSS scale was reviewed to match the diagnostic needs for PD-specific sleep disorders, such as sleep apnea, RBD, and RLS [30]. For that purpose, all night symptoms were divided into three main domains: motor symptoms at night, PD symptoms at night, and disturbed sleep. PDSS-2 score has already been used in studies to identify the changes in sleep quality of PD patients and proved to be less methodology- and sample-dependent compared to other scores [25, 26]. In the present study, we found that PDSS-2 is more understandable and recognized by physicians, and a total score of PDSS-2 in its three domains helps successfully indicate which nocturnal symptoms seriously affect the sleep and life of PD patients. It was also found that the sleep disturbance domain had the largest proportion in the group; this result suggested that attention should be paid to this particular domain in clinical practice, and appropriate intervention methods should be selected. According to the 2019 MDS Parkinson’s Non-motor Symptom Management Consensus, those methods might include PD treatment adjustment, sleep hygiene consultation or prescription of sleeping medication, and the option of continuous positive airway pressure for insomnia patients with obstructive sleep apnea [31].

In our study, PD patients with advanced age, long duration of disease, late Hoehn-Yahr stage, rigidity as the first symptom, RBD, mental illness, and comorbidity were more likely to have nocturnal symptoms. Still, it has to be noted RLS and RBD are part of PDSS-2, and such associations are not surprising. Nevertheless, it is suggested that attention should be paid to the nocturnal symptoms and sleep conditions of PD patients [32, 33] with the factors mentioned above in clinical practice. Simultaneously, this study found that the pharmaceutical treatment amount and medication frequency in the group with nocturnal symptoms were higher compared to the group without nocturnal symptoms.

We noted that education, depression, RBD, PD duration, and Hoehn-Yahr stage were associated with nocturnal symptoms in Chinese PD patients. It is highly advised to focus on the factors with clinical significance and remind doctors and patients of what actions should be taken, such as strengthening doctor-patient communication [34] to improve the understanding of and attention to PD nocturnal symptoms and provide education to patients. The presence of nocturnal symptoms is therefore related to the increase in disease duration and aggravation of other symptoms [10, 17, 28, 35]. It suggests that clinicians should strengthen the monitoring of people at high risk of nocturnal symptoms and pay attention to their treatment, as suggested by similar studies [32, 33]. Depression and RBD are also associated with nocturnal symptoms in PD patients, further indicating the need to evaluate the patient’s mental state and quality of life.

Previous studies showed that anti-PD drugs, in particular L-dopa, adversely affect nocturnal sleep in patients with PD, especially in terms of sleep quality and nocturia [36, 37]. In this study, the patients with nocturnal symptoms were taking more anti-PD drugs than those without nocturnal symptoms, although the multivariable analysis did not identify anti-PD drugs as being associated with the development of nocturnal symptoms. Nevertheless, the top two highest subscores of PDSS-2 were nocturnal motor and PD symptoms. Hence, it is possible that dosing up with anti-PD drugs might cause some resistance to rescuing PD and nocturnal symptoms in the nocturnal symptom group. Furthermore, previous trials revealed that the long-acting dopamine agonist rotigotine rescued some items of the nocturnal motor dysfunction in PDSS-2 [38–40]. Additional studies are necessary to examine the role of anti-PD drugs in developing nocturnal symptoms.

Our study points out that it is necessary to carry out early screening, control, and improve nocturnal symptoms so that patients can obtain a better quality of life. In recent years, with the advancement of medical technology, clinical specialists have access to effective disease monitoring and treatment methods (symptomatic and personalized medicine) through newly developed scales (PDSS-2) and electronic medical equipment (e.g., PSG, wearable devices) [4, 41, 42]. It may help monitor and effectively relieve nocturnal symptoms of PD patients [43].

The fact that there is still insufficient attention to PD nocturnal symptoms and a serious lack of relevant evaluation tools and standards [44, 45] is concerning. Long disease duration means that the same PD patients sometimes are used to evaluate the nocturnal symptoms under different scoring scales and evaluation standards. The evaluation criteria that meet the actual situation and clinical practice in China are needed. It will help identify the nocturnal symptoms of PD in a timely and effective manner and improve the prognosis of nocturnal symptoms in patients with PD.

This study has some limitations. First, it was a cross-sectional study, and it can only analyze the associations, not causality. Second, it was based on the PDSS-2 scale to observe the symptoms of PD patients at night and the PDSS-2 scale to assess night sleep. Although items 13 and 14 include morning tremors, fatigue, and lethargy, they cannot cover the entire night and early morning. Scales evaluated by physicians should be established. Third, the study was only on patients recruited from outpatient departments, and 94% were in the early-to-middle stages. Further studies are needed to explore nocturnal symptoms in patients with severe PD. Finally, in clinical practice, information on nocturnal symptoms of PD is mainly obtained by self-report and scale evaluation, which not only is subjective but also makes it difficult to obtain accurate and comprehensive data. Based on the current research results and the limitations, it should be noted that the PDSS-2 scale is insufficient to obtain full information on nocturnal symptoms in PD patients, while ESS and PSQI demonstrate previous inconsistencies in evaluation. Therefore, new revisions of the existing scales and the development of new scales/questionnaires should be prioritized. Portable wearable sensor equipment might be another promising way to deal with this problem in the future.