International Journal of Neuroscience, 2014; Early Online: 1–7 Copyright © 2014 Informa Healthcare USA, Inc. ISSN: 0020-7454 print / 1543-5245 online DOI: 10.3109/00207454.2014.986573
ORIGINAL ARTICLE
Validation of the nonmotor symptoms questionnaire for Parkinson’s disease: results from a Chinese pilot study
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Hui-juan Li,1 Mei-fen Zhang,2 Miao-xia Chen,1 Ai-ling Hu,1 Ji-bin Li,3 Bo Zhang,3,4 and Wei Liu5 1
Department of Nursing, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; 2 School of Nursing, Sun Yat-sen University, Guangzhou, China; 3 The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China; 4 School of Public Health, Sun Yat-sen University, Guangzhou, China; 5 Guangdong Provincial Key Laboratory of Liver Disease Research, Sun Yat-sen University, Guangzhou, China We performed a cross-sectional study of 82 Chinese patients with Parkinson’s disease (PD) enrolled during an 18-month period. We used a clinical interview to evaluate a Chinese version of the nonmotor symptoms questionnaire (NMSQuest) as an instrument for measuring the nonmotor symptoms (NMS) in Chinese patients with PD. The patients’ cognitive deficit, depression/sleep, disease severity and motor status were assessed based on the mini-mental state examination (MMSE), the Hamilton depression scale (HAMD)/Parkinson’s disease sleep scale (PDSS), the modified Hoehn and Yahr staging scale (H&Y) and the unified Parkinson’s disease rating scale part III (UPDRS III), respectively. Thirty items distributed in nine different domains of the NMSQuest were evaluated, and the association between the NMSQuest and MMSE, H&Y, UPDRS, HAMD and PDSS was identified. Significant correlations were observed between the NMSQuest and disease duration (rs = 0.272, p = 0.013), UPDRS total score (rs = 0.444, p < 0.001), UPDRS II (rs = 0.415, p < 0.001) and UPDRS III (rs = 0.228, p = 0.039). Furthermore, the sleep disorder and mood (depression/anxiety) domain of the NMSQuest were significantly correlated with the PDSS (rs = −0.471, p < 0.001) and HAMD (rs = 0.687, p < 0.001), respectively. Our results indicate that the Chinese version of the NMSQuest, a useful screening tool, can be considered as a comprehensive, practical measure for NMS evaluation in Chinese PD patients. The NMSQuest highlights the prevalence of the wide range of NMS and indicated good responsiveness and interpretability. We strongly recommend routine use of the simplified Chinese version of NMSQuest in this country. KEYWORDS: Parkinson’s disease, nonmotor symptoms, nonmotor symptoms questionnaire, validation
Introduction Parkinson’s disease (PD) is one of the most common neurodegenerative disorders and involved in the disturbance of the central dopaminergic system [1]. PD is commonly characterized by motor symptoms (MS) such as bradykinesia, resting tremor and rigidity. However, various nonmotor symptoms (NMS) such as olfactory problem, rapid eye movement behavior disorder (RBD), constipation, depression, dementia and sleep dysfunction are also highly prevalent and may predate Received 1 September 2014; revised 7 November 2014; accepted 7 November 2014. Correspondence: Meifen Zhang, School of Nursing, Sun Yat-sen University, 74# Zhongshan Road II, Guangzhou, Guangdong 510080, China. Tel/Fax: +86-20-87334776. E-mail: [email protected] or Wei Liu, The Third Affiliated Hospital, Sun Yat-sen University, 600# Tianhe Road, Guangzhou, Guangdong 510630, China. Tel/Fax: +86-20-85253305. E-mail: [email protected]
the clinical diagnosis of PD [2–4]. Some clinicians indicated that NMS, rather than MS, play crucial roles in leading to the deterioration of health-related quality of life (Hr-QoL), and are probably one of the important reasons for the disability in PD [5,6]. In spite of the importance of NMS, these symptoms are normally not well recognized by physicians in clinical practice, and the patients may not notice the connection of their NMS to their disease. While PD is difficult to diagnose until MS occur, the NMS appear throughout the disease course and may even precede MS [7,8]. The lack of NMS recognition may lead to a delay in PD diagnosis and stall a prompt comprehensive disease management strategy. Therefore, it is imperative and crucial to correctly capture and evaluate the NMS in PD patients, especially at the early stage. NMS are usually assessed using several tools, including the unified Parkinson’s disease rating scale 1
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(UPDRS), mini-mental state examination (MMSE) and the Parkinson’s disease sleep scale (PDSS) [9–12]. Recently, Chaudhuri et al. [13] have developed the nonmotor symptoms questionnaire for PD (NMSQuest). The first self-completed 30-item portion is scored as “yes/no” and contains nine domains (including gastrointestinal, urinary, apathy/attention/memory, perceptual problems/hallucinations, mood (depression/anxiety), sexual function, cardiovascular, sleep disorder and miscellaneous) in evaluating NMS in PD. The NMSQuest is a simple instrument that allows patients to indicate their NMS of PD in a practical manner and is in line with other instruments being developed to rapidly assess NMS problems in the clinic. The NMSQuest was not intended to detect changes following treatment or to measure the severity of NMS. Rather, it was devised as a screening tool for physicians and nurses to evaluate NMS. Several lines of evidence have confirmed its validity and reliability in patients from an international cohort from centers in Germany, Spain and the United Kingdom [14]. Contrary to common perception, some NMS such as constipation, postural dizziness, sleep problems, nocturia, daytime sleepiness and restless legs are treatable if they are detected at early stage. In China, some studies also confirmed that the NMSQuest is helpful and useful for evaluating NMS in PD [15,16], but the psychometric characteristics for Chinese version of NMSQest is still need to be created and evaluated before applying the questionnaire in Chinese patients. In this pilot study, we primarily proposed a Chinese version of the NMSQuest (including “yes” and “no” answers) and used it to evaluate the validity of this Chinese version of the scale, and we aimed to compare it with other NMS evaluation criterions. Second, we aimed to demonstrate the NMSQuest’s usefulness as a screening measure for NMS in Chinese patients with PD. The PD NMSQuest is the first PD-specific, validated, international, nonmotor self-administered questionnaire. It is designed to provide a rapid screening tool to examine the presence of NMS, but not intended as a grading for PD [13,17]. The current study highlights the important role of the NMSQuest in clinical practice related to comprehensive care for patients with PD.
Methods Patients This cross-sectional study was conducted at the Department of Neurology of the Affiliated Hospital of Sun Yatsen University, Guangzhou, China, from July 2008 to December 2009. Eighty-two patients with PD, with a mean age (and SD) of 65.0 ± 9.7 including 46 males
Table 1.
Demographic, motor and nonmotor parameters. Total
Clinical parameters Demographic Gender Male Female Age at examination (years) Disease duration (years) Daily L-dopa dosage (mg) H&Y (median) Motor UPDRS III Nonmotor MMSE PDSS HAMD NMSQuest
Mean ± SD/N(%)
Min
Max
82 46 (56.1) 36 (43.9) 65.0 ± 9.7 5.1 ± 4.9 429.7 ± 233.1 2
38 0.04 0 1
82 26 1200 4
16.9 ± 7.0
4
33
27.0 ± 2.2 96.9 ± 24.5 14.1 ± 8.6 17.9 ± 5.0
22 26 0 7
30 144 44 30
SD, standard deviation; H&Y, the modified Hoehn and Yahr staging scale; UPDRS III, the unified Parkinson’s disease rating scale part III; MMSE, mini-mental state examination; PDSS, the Parkinson’s disease sleep scale; HAMD, the Hamilton depression scale; NMSQuest, the nonmotor symptoms questionnaire for Parkinson’s disease (range of possible scores from 0 to 30).
and 36 females (Table 1), were recruited from outpatients and were identified according to the UK PD Brain Bank criteria for the diagnosis of idiopathic PD [18]. Informed consent was obtained from all subjects according to the Declaration of Helsinki (BMJ 1991; 302: 1194). The local Ethics Committee approved the study and the patients gave informed consent for the investigation.
Study design Evaluations and complete neurological examination from outpatients were performed by experienced neurologists. All patients with idiopathic PD in this study fulfilled the criteria of the UK-PDSBB. The exclusion criteria were as follows: (1) PD patients with disability due to neurological disorders other than PD, such as cerebrovascular disease, sequelae or psychosis [11,19]; (2) PD patients with somatic diseases that could have a potential effect on NMS (e.g., pain syndromes, advanced diabetes mellitus, malignancy, renal, hepatic or heart failure, severe anemia, or any other acute or chronic debilitating or life-threatening diseases/states) [19]; (3) PD patients with moderate/severe cognitive impairment that may interfere with the reliability of the NMS self-assessment, as determined by a minimental state examination (MMSE) (the Chinese version of the MMSE) score lower than the median value determined in a reference population-based sample of International Journal of Neuroscience
Validation of NMSQuest in Chinese PD patients
corresponding age and education [20,21]; and (4) individuals who refused to participate in the study.
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Measures The neurologists conducted their evaluations at a regular in-clinic follow-up visit using the following battery of standard assessment measures: a standard demography form, the unified Parkinson’s disease rating scale part III (UPDRS III-motor) [22], the modified Hoehn and Yahr staging scale (H&Y) [23], the Parkinson’s disease sleep scale (PDSS) [24], the mini-mental state examination (MMSE) [25] and the Hamilton depression scale (HAMD) [26]. According to the standard procedure, the NMSQuest was translated into Chinese and then back translated into English by two bilingual university graduates involved in this study, respectively. The NMSQuest is composed of 30 items distributed in nine different domains: gastrointestinal, urinary, apathy/attention/memory, hallucin/delusions, mood (depression/anxiety), sexual function, cardiovascular, sleep disorder, and miscellany. Each item is marked using “yes” or “no.” “Yes” means the subject has experienced the problem during the past 1 month. “No” means the subject has not experienced the problem during the past 1 month. The NMSQuest is a screening tool designed to draw attention to the presence of NMS and initiate further investigation.
Statistical analysis Data quality (missing data, full computable scale scores). A 5% value for missing or noncomputable data was acceptable as the limit. All data for the continuous variables (age, disease duration, daily levodopa dosage, UPDRS III, MMSE, HAMD and PDSS) are shown as the means ± standard deviation, and the categorical variable (gender) is shown as a percentage. The prevalence of each NMS was calculated from the total sample by computing the number of positive responses followed by transformation to a percentage. The sum of an item’s positive responses was transformed into a percentage based on the maximum possible number of positive responses in the domain in order to obtain a standardized ranking of prevalence for each domain. Internal consistency reliability was assessed using Cronbach’s alpha coefficient for subdomains and whole NMSQuest. Spearman’s rank correlation coefficient was used to evaluate the associations among NMSQuest and other evaluations such as PDSS, HAMD, MMSE, disease duration, H&Y, UPDRS total score, UPDRS II and UPDRS III. The strength of the association for correlation coefficients was interpreted as follows: ≤ 0.19, negligible; 0.20 to 0.39, weak; 0.40 to 0.59, moderate; 0.60 to 0.79, C
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strong and ≥ 0.80, very strong [27]. The SPSS 13.0 software (Chicago, IL, USA) was used for statistical analyses. p Values of less than 0.05 were regarded as statistically significant.
Results Patient characteristics In total, 82 PD subjects, including 46 males (56.1%) and 36 females (43.9%), were enrolled in this crosssectional study. The mean age of all patients was 65.0 ± 9.7 years (range, 38 to 82). The mean duration of PD symptoms was 5.1 ± 4.9 years (range, 0.04 to 26), and H&Y stages ranged from 1 to 4. With respect to the levodopa (L-dopa) therapy, the average dosage was 429.7 mg daily (range, 0 to 1200). Details of the demographics of all 82 patients are listed in Table 1.
Prevalence of NMS NMS were widely common in PD patients and all patients with PD reported at least seven NMS (Table 1). The mean value for MMSE was 27.0 ± 2.2 (range, 22 to 30), and for HAMD was 14.1 ± 8.6 (range, 0 to 44). The PDSS included sleep quality, nocturnal restlessness, off-related problems, daytime somnolence, nocturia, and nocturnal psychosis. The mean value for PDSS was 96.9 ± 24.5 (range, 26 to 144). The mean of the total NMSQuest positive symptoms was 17.9 (5.0), ranging from 7 to 30. The percentage of individual NMS, as depicted in the NMSQuest data, is shown in Table 2 with remembering (95.1%) being reported as the most frequent symptom, followed by nocturia (86.6%). Bowel incontinence was the least prevalent NMS (2.4%). The NMSQuest has nine domains, and among these the depression/anxiety domain scored the most “positive” answers (43%, Table 3); while urinary and sexual function were the second and third most prevalent (40% and 39%, Table 3). Gastrointestinal and miscellany were the dimensions with the least frequency of symptoms (0%, Table 3). For each domain, except gastrointestinal and miscellany, there were both patients without symptoms and patients with the maximum number of symptoms. Cronbach’s α coefficient for the NMSQuest was 0.930. The Cronbach’s α coefficient for the nine NMSQuest subdomains (gastrointestinal, urinary, apathy/attention/memory, hallucin/delusions, depression/anxiety, sexual function, cardiovascular, sleep disorder, miscellany) were 0.764, 0.413, 0.678, 0.625, 0.804, 0.296, 0.590, 0.526 and 0.569, respectively. Except for urinary and sexual function subscale, other seven subscales showed acceptable internal consistency
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Table 2.
Individual NMS flagged up by NMSQuest.
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NMSQuest items 1. Dribbling 2. Taste/smelling 3. Swallowing 4. Vomiting 5. Constipation 6. Bowel incontinence 7. Bowel emptying incomplete 8. Urgency 9. Nocturia 10. Pains 11. Weight 12. Remembering 13. Loss of interest 14. Hallucinations 15. Concentrating 16. Sadness and blues 17. Anxiety 18. Sex difficulty 19. Sex drive 20. Dizzy 21. Falling 22. Daytime sleepiness 23. Insomnia 24. Intense vivid dreams 25. Acting out during dreams 26. Restless legs 27. Swelling 28. Sweating 29. Diplopia 30. Delusions
∗
Yes (N)
%
36 37 27 18 55 2 36 45 71 39 24 78 59 12 27 55 50 41 40 31 5 60 64 68 43 62 6 53 32 34
43.9 45.1 32.9 22.0 67.1 2.4 43.9 54.9 86.6 47.6 29.3 95.1 72.0 14.6 32.9 67.1 61.0 50.0 48.8 37.8 6.1 73.2 78.1 82.9 52.4 75.6 7.3 64.6 39.0 41.5
∗
Frequency and percentage calculated on the number of positive responses.
reliability. There was a significant correlation between the NMSQuest and the UPDRS total score (rs = 0.444, p < 0.001, Table 4), between the NMSQuest and the UPDRS II (rs = 0.415, p < 0.001, Table 4), and between the NMSQuest and the UPDRS III (rs = 0.228, p = 0.039, Table 4). In addition, the sleep disorder domain of the NMSQuest was significantly relative to Table 3.
the PDSS (rs = − 0.471, p < 0.001, Table 4), and there was a significant correlation between the depression/anxiety domain of the NMSQuest and the HAMD (rs = 0.687, p < 0.001, Table 4). The correlation coefficients between NMSQuest subdomains and UPDRS scores (daily life/motor), and between NMSQuest subdomains and disease duration were shown in Table 5.
Discussion PD patients displayed many NMS such as cognitive dysfunctions, psychiatric disturbances, sleep disorders, dysautonomia and sensory symptoms, which can all be explained by pathological alterations beyond dopaminergic degenerative of the substantia nigra [28–30]. These NMS can cause problems in the daily life of patients and have a severe impact on their Hr-QoL. Over the past few years, NMS in PD patients have received significant attention during the diagnosis, therapy and evaluation of the Hr-QoL of this disease. Clinically, there is no comprehensive instrument that flags and identifies the clinician to address the range of NMSrelated issues in PD. Therefore, it is necessary to establish an effective tool to provide physicians and nurse specialists a method to screen for NMS in a simple manner. The current study used this self-reporting questionnaire for a comprehensive approach to NMS, across all stages of PD, to determine if the NMSQuest could be used to assess NMS and which aspects of NMS may be evaluated through the NMSQuest in Chinese PD patients. The NMSQuest has “yes” or “no” answers to provide information about the prevalence of NMS in PD patients. One multicenter study by Martinez-Martin et al. has reported the prevalence and wide range of NMS in PD patients through use of the NMSQuest evaluation [17], which is consistent with our current study showing the presence of NMS (Table 2). NMS ranging from sexual dysfunction to cognitive difficulties, such as depression and anxiety, may be experienced by the same
Frequency and distribution of positive answers classified by NMSQuest domains. Positive answers
Domain Gastrointestinal Urinary Apathy/attention/memory Hallucin/delusions Depression/anxiety Sexual function Cardiovascular Sleep disorder Miscellany
Number of items
% on the maximum
Mean ± SD
Range
7 2 3 2 2 2 2 5 5
0 40 22 9 43 39 5 22 0
2.4 ± 1.5 1.4 ± 0.6 2.00 ± 0.8 0.6 ± 0.7 1.3 ± 0.8 1.0 ± 1.0 0.4 ± 0.6 3.6 ± 1.2 2.0 ± 1.0
0–6 0–2 0–3 0–2 0–2 0–2 0–2 0–5 0–4
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Table 4. Correlation of NMSSQuest and aspects with other assessment tools.
Table 5. Correlation of NMSSQuest domains and aspects with other assessment tools.
Measure tools
Measure tools
NMSQuest total score MMSE Disease duration H&Y UPDRS total score UPDRS II (daily life) UPDRS III (motor) Subdomains of NMSQuest Sleep disorder domain of NMSQuest PDSS Depression/anxiety domain of NMSQuest HAMD Apathy/attention/memory domain of NMSQuest MMSE
rs
p Value
−0.033 0.272 0.115 0.444 0.415 0.228
0.772 0.013a 0.302 < 0.001b < 0.001b 0.039a
−0.471
< 0.001b
0.687
0.091
< 0.001b 0.418
rs , Spearman rank correlation coefficients. MMSE, the minimental state examination; H&Y, the modified Hoehn and Yahr staging scale; UPDRS, the unified Parkinson’s disease rating scale; UPDRS II, the unified Parkinson’s disease rating scale part II; UPDRS III, the unified Parkinson’s disease rating scale part III; NMSQuest, the nonmotor symptoms questionnaire for Parkinson’s disease; PDSS, the Parkinson’s disease sleep scale; HAMD, the Hamilton depression scale. a p < 0.05, b p < 0.01.
patients, and this highlights the need for a comprehensive and easy assessment tool. Our result (Table 1) indicated that the NMSQuest mean score was 17.9, which is higher than the previously reported results (mean of 10.9) [31]. The reason for the discrepancy may be due to the following point: as a developing country, the economic and social surroundings are different from those of developed countries; therefore, medical facilities or skills, particularly in the countryside, are not up to date. The PD patients on mainland China did not realize the importance of NMS and general practitioners lack comprehensive and valid tools specific enough to identify and evaluate NMS. As a result, PD patients visited neurologists at a mid to late stage of this disease. Our study revealed that some symptoms (such as constipation, nocturia, remembering, loss of interest, anxiety, daytime sleepiness, insomnia, intense vivid dreams, restless legs, sweating, sadness and blues) were very prevalent (all percentages > 60%, Table 2) in the current Chinese PD patients. “Remembering” and “nocturia” were the most frequent, and some symptoms had not been disclosed to the physicians at all before the NMSQuest was administered. This result further confirmed that the usefulness of the NMSQuest, in a Chinese validated version, could be used as a practical tool in the clinical assessment of NMS in PD and also empowered C
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UPDRS II (daily life) Gastrointestinal Urinary Apathy/attention/memory Hallucin/delusions Depression/anxiety Sexual function Cardiovascular Sleep disorder Miscellany UPDRS III (motor) Gastrointestinal Urinary Apathy/attention/memory Hallucin/delusions Depression/anxiety Sexual function Cardiovascular Sleep disorder Miscellany Disease duration Gastrointestinal Urinary Apathy/attention/memory Hallucin/delusions Depression/anxiety Sexual function Cardiovascular Sleep disorder Miscellany
rs
p Value
0.323 0.197 0.118 0.282 0.251 0.002 0.199 0.140 0.174
0.003b 0.077 0.291 0.010b 0.023a 0.983 0.073 0.211 0.117
0.129 −0.001 −0.011 0.208 0.181 0.034 0.159 0.145 0.230
0.248 0.989 0.924 0.061 0.104 0.763 0.153 0.195 0.038a
0.335 0.129 0.065 0.190 0.224 −0.104 −0.066 0.160 0.256
0.002b 0.249 0.560 0.087 0.043a 0.353 0.557 0.151 0.020a
rs , Spearman rank correlation coefficients. NMSQuest, the nonmotor symptoms questionnaire for Parkinson’s disease; UPDRS II, the unified Parkinson’s disease rating scale part II; UPDRS III, the unified Parkinson’s disease rating scale part III. a p < 0.05, b p < 0.01.
patients to discuss the NMS with their physicians or nurses. In our study, we noticed that among the nine domains in the NMSQuest description the depression/anxiety domain scored the most “positive” answers followed by urinary and sexual function (Table 3). This result indicated that in the current study depression/anxiety (% of the maximum = 43%) may be the most severely influenced and seriously displayed NMS in Chinese PD patients. Interestingly, this result (Table 3) also showed that compared with Martinez-Martin’s study [17], except cardiovascular domain, the scores for all of other domains (such as gastrointestinal, urinary, apathy/attention/memory, hallucinations/delusions, depression/anxiety, sexual function, sleep disorder and miscellany) were higher than those in the MartinezMartin study, indicating that the NMS of the current Chinese PD patients were much more severe than the PD patients in his study. Two reasons likely led to
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the discrepancy of the NMSQuest between Chinese and Western PD subjects. First, there were different social surroundings and medical environments between Chinese and Western populations. As a developing country, some Chinese PD patients lacked sufficient health-care and medical insurance, preventing them from visiting neurologists until the NMS became worse. Second, some general practitioners, especially in the countryside, were unable to efficiently recognize the NMS of PD; thus, PD patients only went to a neurologist when the symptoms worsened. The results of this study further indicated that Chinese doctors should increase their capability of recognizing the NMS in PD. Our result (Table 4) also indicated that the correlation of the NMSQuest with the disease duration (rs = 0.272, p = 0.013), UPDRS total score (rs = 0.444, p < 0.001), UPDRS II (rs = 0.415, p < 0.001) and UPDRS III (rs = 0.228, p = 0.039) were satisfactory and statistically significant. Interestingly, we only observed significant correlations between the sleep disorder domain of the NMSQuest and PDSS, and the depression/anxiety domain of the NMSQuest and HAMD. No significant correlations were found between the apathy/attention/memory domain of the NMSQuest and the MMSE assessment, and between H&Y and the NMSQuest. These findings strongly suggested good construct validity of the NMSQuest on sleep dysfunction, depression and anxiety, disease duration and motor status in PD patients. However, several limitations of this study should be noted: (1) a lack of comparable measures to cover all dimensions represented in the NMS, and age- or sexmatched controls; (2) only a small number of PD patients (82 patients) were recruited, and the disease duration was relatively short (5.1 years) in this study; (3) we exclude those psychotic patients such as anxiety disorder and typical depression, since those patients usually present the similar clinical symptoms during premotor phase of PD, we excluded those patients with atypical PD. However, these exclusions may omit few about 5% missing data of “ideal” PD subjects in this study; (4) Test–retest reliability is important for scale reliability evaluation. In our study, the test–retest was not evaluated. Further study is necessary for the psychometric characteristics of NMSQuest; (5) NMSQ and autonomic symptoms were not correlated; (6) we did not address the identification of NMS in the wearingoff state because most patients were studied in the on state while attending clinics. Therefore, larger studies including more patients with PD and a matched control population to provide a more complete profile still needs to be performed. In addition, patients at different stages of PD in both UPDRS III and H&Y score should be included to compensate for the current shortcomings. Future studies using the NMSQuest to identify NMS in
individual patients should be set up in the off state of the disease. In conclusion, the current study highlights the important role of the NMSQuest in the screening of NMS in clinical neurological practice. The NMSQuest, a simple instrument in line with other instruments to rapidly and simply assess NMS in the clinic [29], may practically allow patients to measure NMS of PD in an easy manner and should be widely introduced to physicians in China. The NMSQuest appears to correlate well with disease progression, indicating good responsiveness and interpretability. We strongly recommend routine use of the simplified Chinese version of the NMSQuest in clinics.
Declaration of Interest The authors have reported no actual or potential conflicts of interest. The authors alone are responsible for the content and writing of the paper. This work was supported by a grant from Bureau of Science and Technology of Guangdong Province (grant no. 2008B080703034).
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21. Cai G, Zhang M, Zhang S, et al. Validity of MMSE and BDRS. J Nervous Mental Dis 1988;14(5):298–9. 22. Fahn S, Elton R. Members of the UPDRS development committee. The unified Parkison’s disease rating scale. Macmillan Health Care Information. Recent Dev Parkinson’s Dis 1987:153–63 and 293–304. 23. Hoehn MM, Yahr MD. Parkinsonism: onset, progression and mortality. Neurology 1967;17(5):427–42. 24. Chaudhuri KR, Pal S, DiMarco A, et al. The Parkinson’s disease sleep scale: a new instrument for assessing sleep and nocturnal disability in Parkinson’s disease. J Neurol Neurosurg Psychiatry 2002;73:629–35. 25. Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12(3):189– 98. 26. Clark DB, Donovan JE. Reliability and validity of the Hamilton Anxiety Rating Scale in an adolescent sample. J Am Acad Child Adolesc Psychiatry 1994;33:354–60. 27. Swinscow D. Correlation and regression. Statistics at square one. 9th ed. London: BMJ Publishing Group; 1997. 28. Braak H, Del Tredici K, Rub U, et al. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 2003;24:197–211. 29. Doorn KJ, Lucassen PJ, Boddeke HW, et al. Emerging roles of microglial activation and non-motor symptoms in Parkinson’s disease. Prog Neurobiol 2012;98:222–38. 30. Xu Y, Yan J, Zhou P, et al. Neurotransmitter receptors and cognitive dysfunction in Alzheimer’s disease and Parkinson’s disease. Prog Neurobiol 2012;97:1–13. 31. Chaudhuri KR, Prieto-Jurcynska C, Naidu Y, et al. The nondeclaration of nonmotor symptoms of Parkinson’s disease to health care professionals: an international study using the nonmotor symptoms questionnaire. Mov Disord 2010;25: 704–9.
ORIGINAL ARTICLE
Validation of the nonmotor symptoms questionnaire for Parkinson’s disease: results from a Chinese pilot study
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Hui-juan Li,1 Mei-fen Zhang,2 Miao-xia Chen,1 Ai-ling Hu,1 Ji-bin Li,3 Bo Zhang,3,4 and Wei Liu5 1
Department of Nursing, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; 2 School of Nursing, Sun Yat-sen University, Guangzhou, China; 3 The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China; 4 School of Public Health, Sun Yat-sen University, Guangzhou, China; 5 Guangdong Provincial Key Laboratory of Liver Disease Research, Sun Yat-sen University, Guangzhou, China We performed a cross-sectional study of 82 Chinese patients with Parkinson’s disease (PD) enrolled during an 18-month period. We used a clinical interview to evaluate a Chinese version of the nonmotor symptoms questionnaire (NMSQuest) as an instrument for measuring the nonmotor symptoms (NMS) in Chinese patients with PD. The patients’ cognitive deficit, depression/sleep, disease severity and motor status were assessed based on the mini-mental state examination (MMSE), the Hamilton depression scale (HAMD)/Parkinson’s disease sleep scale (PDSS), the modified Hoehn and Yahr staging scale (H&Y) and the unified Parkinson’s disease rating scale part III (UPDRS III), respectively. Thirty items distributed in nine different domains of the NMSQuest were evaluated, and the association between the NMSQuest and MMSE, H&Y, UPDRS, HAMD and PDSS was identified. Significant correlations were observed between the NMSQuest and disease duration (rs = 0.272, p = 0.013), UPDRS total score (rs = 0.444, p < 0.001), UPDRS II (rs = 0.415, p < 0.001) and UPDRS III (rs = 0.228, p = 0.039). Furthermore, the sleep disorder and mood (depression/anxiety) domain of the NMSQuest were significantly correlated with the PDSS (rs = −0.471, p < 0.001) and HAMD (rs = 0.687, p < 0.001), respectively. Our results indicate that the Chinese version of the NMSQuest, a useful screening tool, can be considered as a comprehensive, practical measure for NMS evaluation in Chinese PD patients. The NMSQuest highlights the prevalence of the wide range of NMS and indicated good responsiveness and interpretability. We strongly recommend routine use of the simplified Chinese version of NMSQuest in this country. KEYWORDS: Parkinson’s disease, nonmotor symptoms, nonmotor symptoms questionnaire, validation
Introduction Parkinson’s disease (PD) is one of the most common neurodegenerative disorders and involved in the disturbance of the central dopaminergic system [1]. PD is commonly characterized by motor symptoms (MS) such as bradykinesia, resting tremor and rigidity. However, various nonmotor symptoms (NMS) such as olfactory problem, rapid eye movement behavior disorder (RBD), constipation, depression, dementia and sleep dysfunction are also highly prevalent and may predate Received 1 September 2014; revised 7 November 2014; accepted 7 November 2014. Correspondence: Meifen Zhang, School of Nursing, Sun Yat-sen University, 74# Zhongshan Road II, Guangzhou, Guangdong 510080, China. Tel/Fax: +86-20-87334776. E-mail: [email protected] or Wei Liu, The Third Affiliated Hospital, Sun Yat-sen University, 600# Tianhe Road, Guangzhou, Guangdong 510630, China. Tel/Fax: +86-20-85253305. E-mail: [email protected]
the clinical diagnosis of PD [2–4]. Some clinicians indicated that NMS, rather than MS, play crucial roles in leading to the deterioration of health-related quality of life (Hr-QoL), and are probably one of the important reasons for the disability in PD [5,6]. In spite of the importance of NMS, these symptoms are normally not well recognized by physicians in clinical practice, and the patients may not notice the connection of their NMS to their disease. While PD is difficult to diagnose until MS occur, the NMS appear throughout the disease course and may even precede MS [7,8]. The lack of NMS recognition may lead to a delay in PD diagnosis and stall a prompt comprehensive disease management strategy. Therefore, it is imperative and crucial to correctly capture and evaluate the NMS in PD patients, especially at the early stage. NMS are usually assessed using several tools, including the unified Parkinson’s disease rating scale 1
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(UPDRS), mini-mental state examination (MMSE) and the Parkinson’s disease sleep scale (PDSS) [9–12]. Recently, Chaudhuri et al. [13] have developed the nonmotor symptoms questionnaire for PD (NMSQuest). The first self-completed 30-item portion is scored as “yes/no” and contains nine domains (including gastrointestinal, urinary, apathy/attention/memory, perceptual problems/hallucinations, mood (depression/anxiety), sexual function, cardiovascular, sleep disorder and miscellaneous) in evaluating NMS in PD. The NMSQuest is a simple instrument that allows patients to indicate their NMS of PD in a practical manner and is in line with other instruments being developed to rapidly assess NMS problems in the clinic. The NMSQuest was not intended to detect changes following treatment or to measure the severity of NMS. Rather, it was devised as a screening tool for physicians and nurses to evaluate NMS. Several lines of evidence have confirmed its validity and reliability in patients from an international cohort from centers in Germany, Spain and the United Kingdom [14]. Contrary to common perception, some NMS such as constipation, postural dizziness, sleep problems, nocturia, daytime sleepiness and restless legs are treatable if they are detected at early stage. In China, some studies also confirmed that the NMSQuest is helpful and useful for evaluating NMS in PD [15,16], but the psychometric characteristics for Chinese version of NMSQest is still need to be created and evaluated before applying the questionnaire in Chinese patients. In this pilot study, we primarily proposed a Chinese version of the NMSQuest (including “yes” and “no” answers) and used it to evaluate the validity of this Chinese version of the scale, and we aimed to compare it with other NMS evaluation criterions. Second, we aimed to demonstrate the NMSQuest’s usefulness as a screening measure for NMS in Chinese patients with PD. The PD NMSQuest is the first PD-specific, validated, international, nonmotor self-administered questionnaire. It is designed to provide a rapid screening tool to examine the presence of NMS, but not intended as a grading for PD [13,17]. The current study highlights the important role of the NMSQuest in clinical practice related to comprehensive care for patients with PD.
Methods Patients This cross-sectional study was conducted at the Department of Neurology of the Affiliated Hospital of Sun Yatsen University, Guangzhou, China, from July 2008 to December 2009. Eighty-two patients with PD, with a mean age (and SD) of 65.0 ± 9.7 including 46 males
Table 1.
Demographic, motor and nonmotor parameters. Total
Clinical parameters Demographic Gender Male Female Age at examination (years) Disease duration (years) Daily L-dopa dosage (mg) H&Y (median) Motor UPDRS III Nonmotor MMSE PDSS HAMD NMSQuest
Mean ± SD/N(%)
Min
Max
82 46 (56.1) 36 (43.9) 65.0 ± 9.7 5.1 ± 4.9 429.7 ± 233.1 2
38 0.04 0 1
82 26 1200 4
16.9 ± 7.0
4
33
27.0 ± 2.2 96.9 ± 24.5 14.1 ± 8.6 17.9 ± 5.0
22 26 0 7
30 144 44 30
SD, standard deviation; H&Y, the modified Hoehn and Yahr staging scale; UPDRS III, the unified Parkinson’s disease rating scale part III; MMSE, mini-mental state examination; PDSS, the Parkinson’s disease sleep scale; HAMD, the Hamilton depression scale; NMSQuest, the nonmotor symptoms questionnaire for Parkinson’s disease (range of possible scores from 0 to 30).
and 36 females (Table 1), were recruited from outpatients and were identified according to the UK PD Brain Bank criteria for the diagnosis of idiopathic PD [18]. Informed consent was obtained from all subjects according to the Declaration of Helsinki (BMJ 1991; 302: 1194). The local Ethics Committee approved the study and the patients gave informed consent for the investigation.
Study design Evaluations and complete neurological examination from outpatients were performed by experienced neurologists. All patients with idiopathic PD in this study fulfilled the criteria of the UK-PDSBB. The exclusion criteria were as follows: (1) PD patients with disability due to neurological disorders other than PD, such as cerebrovascular disease, sequelae or psychosis [11,19]; (2) PD patients with somatic diseases that could have a potential effect on NMS (e.g., pain syndromes, advanced diabetes mellitus, malignancy, renal, hepatic or heart failure, severe anemia, or any other acute or chronic debilitating or life-threatening diseases/states) [19]; (3) PD patients with moderate/severe cognitive impairment that may interfere with the reliability of the NMS self-assessment, as determined by a minimental state examination (MMSE) (the Chinese version of the MMSE) score lower than the median value determined in a reference population-based sample of International Journal of Neuroscience
Validation of NMSQuest in Chinese PD patients
corresponding age and education [20,21]; and (4) individuals who refused to participate in the study.
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Measures The neurologists conducted their evaluations at a regular in-clinic follow-up visit using the following battery of standard assessment measures: a standard demography form, the unified Parkinson’s disease rating scale part III (UPDRS III-motor) [22], the modified Hoehn and Yahr staging scale (H&Y) [23], the Parkinson’s disease sleep scale (PDSS) [24], the mini-mental state examination (MMSE) [25] and the Hamilton depression scale (HAMD) [26]. According to the standard procedure, the NMSQuest was translated into Chinese and then back translated into English by two bilingual university graduates involved in this study, respectively. The NMSQuest is composed of 30 items distributed in nine different domains: gastrointestinal, urinary, apathy/attention/memory, hallucin/delusions, mood (depression/anxiety), sexual function, cardiovascular, sleep disorder, and miscellany. Each item is marked using “yes” or “no.” “Yes” means the subject has experienced the problem during the past 1 month. “No” means the subject has not experienced the problem during the past 1 month. The NMSQuest is a screening tool designed to draw attention to the presence of NMS and initiate further investigation.
Statistical analysis Data quality (missing data, full computable scale scores). A 5% value for missing or noncomputable data was acceptable as the limit. All data for the continuous variables (age, disease duration, daily levodopa dosage, UPDRS III, MMSE, HAMD and PDSS) are shown as the means ± standard deviation, and the categorical variable (gender) is shown as a percentage. The prevalence of each NMS was calculated from the total sample by computing the number of positive responses followed by transformation to a percentage. The sum of an item’s positive responses was transformed into a percentage based on the maximum possible number of positive responses in the domain in order to obtain a standardized ranking of prevalence for each domain. Internal consistency reliability was assessed using Cronbach’s alpha coefficient for subdomains and whole NMSQuest. Spearman’s rank correlation coefficient was used to evaluate the associations among NMSQuest and other evaluations such as PDSS, HAMD, MMSE, disease duration, H&Y, UPDRS total score, UPDRS II and UPDRS III. The strength of the association for correlation coefficients was interpreted as follows: ≤ 0.19, negligible; 0.20 to 0.39, weak; 0.40 to 0.59, moderate; 0.60 to 0.79, C
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strong and ≥ 0.80, very strong [27]. The SPSS 13.0 software (Chicago, IL, USA) was used for statistical analyses. p Values of less than 0.05 were regarded as statistically significant.
Results Patient characteristics In total, 82 PD subjects, including 46 males (56.1%) and 36 females (43.9%), were enrolled in this crosssectional study. The mean age of all patients was 65.0 ± 9.7 years (range, 38 to 82). The mean duration of PD symptoms was 5.1 ± 4.9 years (range, 0.04 to 26), and H&Y stages ranged from 1 to 4. With respect to the levodopa (L-dopa) therapy, the average dosage was 429.7 mg daily (range, 0 to 1200). Details of the demographics of all 82 patients are listed in Table 1.
Prevalence of NMS NMS were widely common in PD patients and all patients with PD reported at least seven NMS (Table 1). The mean value for MMSE was 27.0 ± 2.2 (range, 22 to 30), and for HAMD was 14.1 ± 8.6 (range, 0 to 44). The PDSS included sleep quality, nocturnal restlessness, off-related problems, daytime somnolence, nocturia, and nocturnal psychosis. The mean value for PDSS was 96.9 ± 24.5 (range, 26 to 144). The mean of the total NMSQuest positive symptoms was 17.9 (5.0), ranging from 7 to 30. The percentage of individual NMS, as depicted in the NMSQuest data, is shown in Table 2 with remembering (95.1%) being reported as the most frequent symptom, followed by nocturia (86.6%). Bowel incontinence was the least prevalent NMS (2.4%). The NMSQuest has nine domains, and among these the depression/anxiety domain scored the most “positive” answers (43%, Table 3); while urinary and sexual function were the second and third most prevalent (40% and 39%, Table 3). Gastrointestinal and miscellany were the dimensions with the least frequency of symptoms (0%, Table 3). For each domain, except gastrointestinal and miscellany, there were both patients without symptoms and patients with the maximum number of symptoms. Cronbach’s α coefficient for the NMSQuest was 0.930. The Cronbach’s α coefficient for the nine NMSQuest subdomains (gastrointestinal, urinary, apathy/attention/memory, hallucin/delusions, depression/anxiety, sexual function, cardiovascular, sleep disorder, miscellany) were 0.764, 0.413, 0.678, 0.625, 0.804, 0.296, 0.590, 0.526 and 0.569, respectively. Except for urinary and sexual function subscale, other seven subscales showed acceptable internal consistency
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Table 2.
Individual NMS flagged up by NMSQuest.
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NMSQuest items 1. Dribbling 2. Taste/smelling 3. Swallowing 4. Vomiting 5. Constipation 6. Bowel incontinence 7. Bowel emptying incomplete 8. Urgency 9. Nocturia 10. Pains 11. Weight 12. Remembering 13. Loss of interest 14. Hallucinations 15. Concentrating 16. Sadness and blues 17. Anxiety 18. Sex difficulty 19. Sex drive 20. Dizzy 21. Falling 22. Daytime sleepiness 23. Insomnia 24. Intense vivid dreams 25. Acting out during dreams 26. Restless legs 27. Swelling 28. Sweating 29. Diplopia 30. Delusions
∗
Yes (N)
%
36 37 27 18 55 2 36 45 71 39 24 78 59 12 27 55 50 41 40 31 5 60 64 68 43 62 6 53 32 34
43.9 45.1 32.9 22.0 67.1 2.4 43.9 54.9 86.6 47.6 29.3 95.1 72.0 14.6 32.9 67.1 61.0 50.0 48.8 37.8 6.1 73.2 78.1 82.9 52.4 75.6 7.3 64.6 39.0 41.5
∗
Frequency and percentage calculated on the number of positive responses.
reliability. There was a significant correlation between the NMSQuest and the UPDRS total score (rs = 0.444, p < 0.001, Table 4), between the NMSQuest and the UPDRS II (rs = 0.415, p < 0.001, Table 4), and between the NMSQuest and the UPDRS III (rs = 0.228, p = 0.039, Table 4). In addition, the sleep disorder domain of the NMSQuest was significantly relative to Table 3.
the PDSS (rs = − 0.471, p < 0.001, Table 4), and there was a significant correlation between the depression/anxiety domain of the NMSQuest and the HAMD (rs = 0.687, p < 0.001, Table 4). The correlation coefficients between NMSQuest subdomains and UPDRS scores (daily life/motor), and between NMSQuest subdomains and disease duration were shown in Table 5.
Discussion PD patients displayed many NMS such as cognitive dysfunctions, psychiatric disturbances, sleep disorders, dysautonomia and sensory symptoms, which can all be explained by pathological alterations beyond dopaminergic degenerative of the substantia nigra [28–30]. These NMS can cause problems in the daily life of patients and have a severe impact on their Hr-QoL. Over the past few years, NMS in PD patients have received significant attention during the diagnosis, therapy and evaluation of the Hr-QoL of this disease. Clinically, there is no comprehensive instrument that flags and identifies the clinician to address the range of NMSrelated issues in PD. Therefore, it is necessary to establish an effective tool to provide physicians and nurse specialists a method to screen for NMS in a simple manner. The current study used this self-reporting questionnaire for a comprehensive approach to NMS, across all stages of PD, to determine if the NMSQuest could be used to assess NMS and which aspects of NMS may be evaluated through the NMSQuest in Chinese PD patients. The NMSQuest has “yes” or “no” answers to provide information about the prevalence of NMS in PD patients. One multicenter study by Martinez-Martin et al. has reported the prevalence and wide range of NMS in PD patients through use of the NMSQuest evaluation [17], which is consistent with our current study showing the presence of NMS (Table 2). NMS ranging from sexual dysfunction to cognitive difficulties, such as depression and anxiety, may be experienced by the same
Frequency and distribution of positive answers classified by NMSQuest domains. Positive answers
Domain Gastrointestinal Urinary Apathy/attention/memory Hallucin/delusions Depression/anxiety Sexual function Cardiovascular Sleep disorder Miscellany
Number of items
% on the maximum
Mean ± SD
Range
7 2 3 2 2 2 2 5 5
0 40 22 9 43 39 5 22 0
2.4 ± 1.5 1.4 ± 0.6 2.00 ± 0.8 0.6 ± 0.7 1.3 ± 0.8 1.0 ± 1.0 0.4 ± 0.6 3.6 ± 1.2 2.0 ± 1.0
0–6 0–2 0–3 0–2 0–2 0–2 0–2 0–5 0–4
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Table 4. Correlation of NMSSQuest and aspects with other assessment tools.
Table 5. Correlation of NMSSQuest domains and aspects with other assessment tools.
Measure tools
Measure tools
NMSQuest total score MMSE Disease duration H&Y UPDRS total score UPDRS II (daily life) UPDRS III (motor) Subdomains of NMSQuest Sleep disorder domain of NMSQuest PDSS Depression/anxiety domain of NMSQuest HAMD Apathy/attention/memory domain of NMSQuest MMSE
rs
p Value
−0.033 0.272 0.115 0.444 0.415 0.228
0.772 0.013a 0.302 < 0.001b < 0.001b 0.039a
−0.471
< 0.001b
0.687
0.091
< 0.001b 0.418
rs , Spearman rank correlation coefficients. MMSE, the minimental state examination; H&Y, the modified Hoehn and Yahr staging scale; UPDRS, the unified Parkinson’s disease rating scale; UPDRS II, the unified Parkinson’s disease rating scale part II; UPDRS III, the unified Parkinson’s disease rating scale part III; NMSQuest, the nonmotor symptoms questionnaire for Parkinson’s disease; PDSS, the Parkinson’s disease sleep scale; HAMD, the Hamilton depression scale. a p < 0.05, b p < 0.01.
patients, and this highlights the need for a comprehensive and easy assessment tool. Our result (Table 1) indicated that the NMSQuest mean score was 17.9, which is higher than the previously reported results (mean of 10.9) [31]. The reason for the discrepancy may be due to the following point: as a developing country, the economic and social surroundings are different from those of developed countries; therefore, medical facilities or skills, particularly in the countryside, are not up to date. The PD patients on mainland China did not realize the importance of NMS and general practitioners lack comprehensive and valid tools specific enough to identify and evaluate NMS. As a result, PD patients visited neurologists at a mid to late stage of this disease. Our study revealed that some symptoms (such as constipation, nocturia, remembering, loss of interest, anxiety, daytime sleepiness, insomnia, intense vivid dreams, restless legs, sweating, sadness and blues) were very prevalent (all percentages > 60%, Table 2) in the current Chinese PD patients. “Remembering” and “nocturia” were the most frequent, and some symptoms had not been disclosed to the physicians at all before the NMSQuest was administered. This result further confirmed that the usefulness of the NMSQuest, in a Chinese validated version, could be used as a practical tool in the clinical assessment of NMS in PD and also empowered C
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UPDRS II (daily life) Gastrointestinal Urinary Apathy/attention/memory Hallucin/delusions Depression/anxiety Sexual function Cardiovascular Sleep disorder Miscellany UPDRS III (motor) Gastrointestinal Urinary Apathy/attention/memory Hallucin/delusions Depression/anxiety Sexual function Cardiovascular Sleep disorder Miscellany Disease duration Gastrointestinal Urinary Apathy/attention/memory Hallucin/delusions Depression/anxiety Sexual function Cardiovascular Sleep disorder Miscellany
rs
p Value
0.323 0.197 0.118 0.282 0.251 0.002 0.199 0.140 0.174
0.003b 0.077 0.291 0.010b 0.023a 0.983 0.073 0.211 0.117
0.129 −0.001 −0.011 0.208 0.181 0.034 0.159 0.145 0.230
0.248 0.989 0.924 0.061 0.104 0.763 0.153 0.195 0.038a
0.335 0.129 0.065 0.190 0.224 −0.104 −0.066 0.160 0.256
0.002b 0.249 0.560 0.087 0.043a 0.353 0.557 0.151 0.020a
rs , Spearman rank correlation coefficients. NMSQuest, the nonmotor symptoms questionnaire for Parkinson’s disease; UPDRS II, the unified Parkinson’s disease rating scale part II; UPDRS III, the unified Parkinson’s disease rating scale part III. a p < 0.05, b p < 0.01.
patients to discuss the NMS with their physicians or nurses. In our study, we noticed that among the nine domains in the NMSQuest description the depression/anxiety domain scored the most “positive” answers followed by urinary and sexual function (Table 3). This result indicated that in the current study depression/anxiety (% of the maximum = 43%) may be the most severely influenced and seriously displayed NMS in Chinese PD patients. Interestingly, this result (Table 3) also showed that compared with Martinez-Martin’s study [17], except cardiovascular domain, the scores for all of other domains (such as gastrointestinal, urinary, apathy/attention/memory, hallucinations/delusions, depression/anxiety, sexual function, sleep disorder and miscellany) were higher than those in the MartinezMartin study, indicating that the NMS of the current Chinese PD patients were much more severe than the PD patients in his study. Two reasons likely led to
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the discrepancy of the NMSQuest between Chinese and Western PD subjects. First, there were different social surroundings and medical environments between Chinese and Western populations. As a developing country, some Chinese PD patients lacked sufficient health-care and medical insurance, preventing them from visiting neurologists until the NMS became worse. Second, some general practitioners, especially in the countryside, were unable to efficiently recognize the NMS of PD; thus, PD patients only went to a neurologist when the symptoms worsened. The results of this study further indicated that Chinese doctors should increase their capability of recognizing the NMS in PD. Our result (Table 4) also indicated that the correlation of the NMSQuest with the disease duration (rs = 0.272, p = 0.013), UPDRS total score (rs = 0.444, p < 0.001), UPDRS II (rs = 0.415, p < 0.001) and UPDRS III (rs = 0.228, p = 0.039) were satisfactory and statistically significant. Interestingly, we only observed significant correlations between the sleep disorder domain of the NMSQuest and PDSS, and the depression/anxiety domain of the NMSQuest and HAMD. No significant correlations were found between the apathy/attention/memory domain of the NMSQuest and the MMSE assessment, and between H&Y and the NMSQuest. These findings strongly suggested good construct validity of the NMSQuest on sleep dysfunction, depression and anxiety, disease duration and motor status in PD patients. However, several limitations of this study should be noted: (1) a lack of comparable measures to cover all dimensions represented in the NMS, and age- or sexmatched controls; (2) only a small number of PD patients (82 patients) were recruited, and the disease duration was relatively short (5.1 years) in this study; (3) we exclude those psychotic patients such as anxiety disorder and typical depression, since those patients usually present the similar clinical symptoms during premotor phase of PD, we excluded those patients with atypical PD. However, these exclusions may omit few about 5% missing data of “ideal” PD subjects in this study; (4) Test–retest reliability is important for scale reliability evaluation. In our study, the test–retest was not evaluated. Further study is necessary for the psychometric characteristics of NMSQuest; (5) NMSQ and autonomic symptoms were not correlated; (6) we did not address the identification of NMS in the wearingoff state because most patients were studied in the on state while attending clinics. Therefore, larger studies including more patients with PD and a matched control population to provide a more complete profile still needs to be performed. In addition, patients at different stages of PD in both UPDRS III and H&Y score should be included to compensate for the current shortcomings. Future studies using the NMSQuest to identify NMS in
individual patients should be set up in the off state of the disease. In conclusion, the current study highlights the important role of the NMSQuest in the screening of NMS in clinical neurological practice. The NMSQuest, a simple instrument in line with other instruments to rapidly and simply assess NMS in the clinic [29], may practically allow patients to measure NMS of PD in an easy manner and should be widely introduced to physicians in China. The NMSQuest appears to correlate well with disease progression, indicating good responsiveness and interpretability. We strongly recommend routine use of the simplified Chinese version of the NMSQuest in clinics.
Declaration of Interest The authors have reported no actual or potential conflicts of interest. The authors alone are responsible for the content and writing of the paper. This work was supported by a grant from Bureau of Science and Technology of Guangdong Province (grant no. 2008B080703034).
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