# Staging Parkinson’s Disease Combining Motor and Nonmotor Symptoms Correlates with Disability and Quality of Life

Authors: D. Santos García; T. De Deus Fonticoba; J. M. Paz González; C. Cores Bartolomé; L. Valdés Aymerich; J. G. Muñoz Enríquez; E. Suárez; S. Jesús; M. Aguilar; P. Pastor; L. L. Planellas; M. Cosgaya; J. García Caldentey; N. Caballol; I. Legarda; J. Hernández Vara; I. Cabo; L. López Manzanares; I. González Aramburu; M. A. Ávila Rivera; M. J. Catalán; V. Nogueira; V. Puente; J. M. García Moreno; C. Borrué; B. Solano Vila; M. Álvarez Sauco; L. Vela; S. Escalante; E. Cubo; F. Carrillo Padilla; J. C. Martínez Castrillo; P. Sánchez Alonso; M. G. Alonso Losada; N. López Ariztegui; I. Gastón; J. Kulisevsky; M. Blázquez Estrada; M. Seijo; J. Rúiz Martínez; C. Valero; M. Kurtis; O. de Fábregues; J. González Ardura; C. Ordás; L. López Díaz; P. Mir; P. Martinez-Martin; COPPADIS Study Group
Journal: Parkinson’s Disease
 (2021)

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## Abstract

Introduction. In a degenerative disorder such as Parkinson’s disease (PD), it is important to establish clinical stages that allow to know the course of the disease. Our aim was to analyze whether a scale combining Hoehn and Yahr’s motor stage (H&Y) and the nonmotor symptoms burden (NMSB) (assessed by the nonmotor symptoms scale (NMSS)) provides information about the disability and the patient’s quality of life (QoL) with regard to a defined clinical stage. Materials and Methods. Cross-sectional study in which 603 PD patients from the COPPADIS cohort were classified according to H&Y (1, stage I; 2, stage II; 3, stage III; 4, stage IV/V) and NMSB (A: NMSS = 0–20; B: NMSS = 21–40; C: NMSS = 41–70; D: NMSS ≥ 71) in 16 stages (HY.NMSB, from 1A to 4D). QoL was assessed with the PDQ-39SI, PQ-10, and EUROHIS-QOL8 and disability with the Schwab&England ADL (Activities of Daily Living) scale. Results. A worse QoL and greater disability were observed at a higher stage of H&Y and NMSB (p<0.0001). Combining both (HY.NMSB), patients in stages 1C and 1D and 2C and 2D had significantly worse QoL and/or less autonomy for ADL than those in stages 2A and 2B and 3A and 3B, respectively (p<0.005; e.g., PDQ-39SI in 1D [n = 15] vs 2A [n = 101]: 28.6 ± 17.1 vs 7.9 ± 5.8; p<0.0001). Conclusion. The HY.NMSB scale is simple and reflects the degree of patient involvement more accurately than the H&Y. Patients with a lower H&Y stage may be more affected if they have a greater NMS burden.


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## Body

## 1. Introduction

Parkinson’s disease (PD) is a progressive neurodegenerative disorder causing motor and nonmotor symptoms (NMS) that result in disability, loss of patient autonomy, and caregiver burden [1]. In a degenerative disease, it is important to establish clinical stages that allow the determination of disease progression for a patient based on different specific symptoms. Ideally, this clinical graduation should be simple to carry out so that it can be used universally in clinical practice. In the case of PD, and based on the classic motor symptoms of the disease, the Hoehn and Yahr (H&Y) scale is used to describe the progression of PD [2]. The scale was originally described in 1967 and included stages 1 through 5. It has since been modified with the addition of stages 1.5 and 2.5 to help describe the intermediate course of the disease [3]. This rating system has been largely supplemented by, firstly, the Unified Parkinson’s Disease Rating Scale (UPDRS) [4], and more recently, the MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) [5], which assess limitation of Activities of Daily Living (ADL) and NMS. However, evaluating the patient using the UPDRS and/or MDS-UPDRS takes time; specialization is required and, importantly, do not allow the patient to be classified into a clearly differentiated stage, and several NMS are not included. Validated tools for assessing NMS such as the NMSQuest [6] and the nonmotor symptoms scale (NMSS) [7] are used both in trials and in clinical practice. Furthermore, it has been demonstrated that NMS are an important determinant and deteriorating factor of the quality of life (QoL) of PD patients [8, 9]. Not only motor symptoms but also NMS increase in their severity and burden over time, increasing patients’ disability, with additional worsening of their QoL, as well as caregivers’ burden and consequential consumption of social resources by increasing societal costs. That is why for staging PD it would be necessary to combine a motor with a nonmotor scale, which would allow the patient to be classified into stages considering both the degree of motor and nonmotor involvement.Recently, it has been suggested that gradation of PD according to the motor impairment and burden of NMS is an unmet need for an appropriate management of patients [10]. Ray Chaudhuri et al. proposed a PD classification by H&Y staging and NMS burden level and demonstrated a correlation of both H&Y staging and NMS burden to disability and QoL [11]. However, QoL and autonomy for ADL regarding the stage considering both together, motor and nonmotor stages, were not analyzed. The H&Y scale provides quick information about the patient's condition, but since it does not include NMS, it is not very sensitive to reflect the real impact of that condition. Our hypothesis is that a patient with a lower H&Y stage but a greater NMS burden may present a worse QoL and greater disability than another patient with a more advanced H&Y stage but a lower NMS burden, so it would be beneficial to combine both aspects on a scale. The aim of this study was to classify PD patients from the COPPADIS cohort [12, 13], regarding H&Y and NMS burden combined in a specific scale (HY.NMSB), and to compare QoL and autonomy for ADL between patients in a different HY.NMSB stages.


## 2. Materials and Methods

PD patients recruited from 35 centers of Spain from the COPPADIS cohort [13] from January 2016 to November 2017 were included in the study. Methodology about COPPADIS-2015 study can be consulted in https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-016-0548-9.This is a multicenter, observational, longitudinal-prospective, 5-year follow-up study designed to analyze disease progression in a Spanish population of PD patients. The data for the present study (cross-sectional study) were obtained from the baseline evaluation. All patients included were diagnosed according to UK PD Brain Bank criteria. Exclusion criteria were as follows: non-PD parkinsonism, dementia (Mini Mental State Examination (MMSE) < 26), age <18 or >75 years, inability to read or understand the questionnaires, to be receiving any advanced therapy (continuous infusion of levodopa or apomorphine and/or with deep brain stimulation), and the presence of comorbidity, sequelae, or any disorder that could interfere with the assessment.Information on sociodemographic aspects, factors related to PD, comorbidity, and treatment was collected. Motor and NMS were evaluated using different validated scales [12]. In patients with motor fluctuations, the motor assessment (H&Y and UPDRS) was conducted during the OFF state (without medication in the last 12 hours; H&Y-OFF and UPDRS-III-OFF) and during the ON state (H&Y-ON and UPDRS-III-ON). However, in patients without motor fluctuations, it was only performed without medication (first thing in the morning without taking medication in the previous 12 hours). Moreover, in PD patients with motor fluctuations, the nonmotor assessment was conducted during the ON state [12]. The NMSS [7] was used for assessing NMS. This includes 30 items, each with a different nonmotor symptom. The symptoms refer to the 4 weeks prior to assessment. The total score for each item is the result of multiplying the frequency (0, never; 1, rarely; 2, often; 3, frequent; 4, very often) x severity (1, mild; 2, moderate; 3, severe) and will vary from 0 to 12 points. The scale score ranges from 0 to 360 points. The items are grouped into 9 different domains: (1) cardiovascular (items 1 and 2; score, 0 to 24); (2) sleep/fatigue (items 3, 4, 5, and 6; score, 0 to 48); (3) depression/apathy (items 7, 8, 9, 10, 11, and 12; score, 0 to 72); (4) perceptual problems/hallucinations (items 13, 14, and 15; score, 0 to 36); (5) attention/memory (items 16, 17, and 18; score, 0 to 36); (6) gastrointestinal tract (items 19, 20, and 21; score, 0 to 36); (7) urinary symptoms (items 22, 23, and 24; score, 0 to 36); (8) sexual dysfunction (items 25 and 26; score, 0 to 24); (9) miscellaneous (items 27, 28, 29, and 30; score, 0 to 48).Three different instruments were used to assess QoL: (1) the PDQ-39 [14]; (2) a rating of global perceived QoL (PQ-10) on a scale from 0 (worst) to 10 (best) [8, 15]; and (3) the EUROHIS-QOL8 [16]. The PDQ-39 is a PD-specific questionnaire that assesses the patients’ health-related QoL. There are 39 items grouped into 8 domains: (1) mobility (items 1 to 10); (2) Activities of Daily Living (items 11 to 16); (3) emotional well-being (items 17 to 22); (4) stigma (items 23 to 26); (5) social support (items 27 to 29); (6) cognition (items 30 to 33); (7) communication (items 34 to 36); and (8) pain and discomfort (items 37 to 39). For each item, the score may range from 0 (never) to 4 (always). The symptoms refer to the 4 weeks prior to assessment. Domain total scores are expressed as a percentage of the corresponding maximum possible score, and a Summary Index is obtained as average of the domain scores. The EUROHIS-QOL8 is an 8-item global QoL questionnaire (quality of life, health status, energy, autonomy for Activities of Daily Living, self-esteem, social relationships, economic capacity, and habitat) derived from the WHOQOL-BREF. For each item, the score ranges from 0 (not at all) to 5 (completely). The total score is expressed as the mean of the individual scores. A higher score indicates a better QoL. The Schwab and England Activities of Daily Living Scale (ADLS) was used for assessing disability [17]. Functional dependency was defined as an ADLS score less than 80% (80% = completely independent; 70% = not completely independent) [18].


### 2.1. Data analysis

Data were processed using SPSS 20.0 for Windows. NMS burden was defined as follows: mild (NMSS 1-20); moderate (NMSS 21-40); severe (NMSS 41-70); and very severe (NMSS > 70) [10]. Each domain of the NMSS was expressed as a percentage: (score/total score) × 100. The patients were classified according to H&Y-OFF (1, stage I; 2, stage II; 3, stage III; 4, stage IV /V) and NMS burden (A: 0-20; B: 21-40; C: 41-70; D: ≥ 71) in 16 stages (HY.NMSB): 1A, 1B, 1C, 1D, 2A, 2B, 2C, 2D, 3A, 3B, 3C, 3D, 4A, 4B, 4C, and 4D. PDQ-39 was expressed as a Summary Index (PDQ-39SI): (score/156) × 100. For comparisons between patients with a different H&Y stage, NMS burden stage, and/or HY.NMSB stage, chi-squared, ANOVA, and/or Mann–Whitney–Wilcoxon test were applied. With the aim of determining if the HY.NMSB contributes to the patient’s QoL independently of other factors, a multiple regression analysis was conducted (PDQ-39SI as dependent variable). A p value < 0.05 was considered significant.


### 2.2. Standard Protocol Approvals, Registrations, and Patient Consent

For this study, we received approval from theComité de Ética de la Investigación Clínica de Galicia from Spain (2014/534; 02/DEC/2014). Written informed consents from all participants in this study were obtained before the start of the study. COPPADIS-2015 was classified by the AEMPS (Agencia Española del Medicamento y Productos Sanitarios) as a postauthorization prospective follow-up study with the code COH-PAK-2014-01.


## 2.1. Data analysis

Data were processed using SPSS 20.0 for Windows. NMS burden was defined as follows: mild (NMSS 1-20); moderate (NMSS 21-40); severe (NMSS 41-70); and very severe (NMSS > 70) [10]. Each domain of the NMSS was expressed as a percentage: (score/total score) × 100. The patients were classified according to H&Y-OFF (1, stage I; 2, stage II; 3, stage III; 4, stage IV /V) and NMS burden (A: 0-20; B: 21-40; C: 41-70; D: ≥ 71) in 16 stages (HY.NMSB): 1A, 1B, 1C, 1D, 2A, 2B, 2C, 2D, 3A, 3B, 3C, 3D, 4A, 4B, 4C, and 4D. PDQ-39 was expressed as a Summary Index (PDQ-39SI): (score/156) × 100. For comparisons between patients with a different H&Y stage, NMS burden stage, and/or HY.NMSB stage, chi-squared, ANOVA, and/or Mann–Whitney–Wilcoxon test were applied. With the aim of determining if the HY.NMSB contributes to the patient’s QoL independently of other factors, a multiple regression analysis was conducted (PDQ-39SI as dependent variable). A p value < 0.05 was considered significant.


## 2.2. Standard Protocol Approvals, Registrations, and Patient Consent

For this study, we received approval from theComité de Ética de la Investigación Clínica de Galicia from Spain (2014/534; 02/DEC/2014). Written informed consents from all participants in this study were obtained before the start of the study. COPPADIS-2015 was classified by the AEMPS (Agencia Española del Medicamento y Productos Sanitarios) as a postauthorization prospective follow-up study with the code COH-PAK-2014-01.


## 3. Results

A total of 603 PD patients (62.7 ± 8.9 years old; 59.5% males) from the COPPADIS cohort were included in the analysis. The mean disease duration was 5.7 ± 4.5 years. One-hundred and twenty-eight (22.9%) patients were in stage I of H&Y, 407 (67.5%) in stage II of H&Y, 49 (8.1%) in stage III of H&Y, and only 9 (1.5%) in stage IV/V of H&Y. The mean NMSS total score was 46.7 ± 38.2, presenting 162 (26.9%) patients with mild NMS burden, 174 (28.8%) with moderate NMS burden, 140 (23.2%) with severe NMS burden, and 127 (21.1%) with very severe NMS burden. No patient presented absence of nonmotor symptoms (NMSS = 0). Data about PD-related variables are shown in Table SM1. When H&Y and NMS burden were combined (HY.NMSB), a higher percentage of patients with severe or very severe NMS burden in advanced H&Y stages (III and/or IV/V) (p<0.0001) was observed (Figure 1).Figure 1
Total number (a) and percentage (b) of PD patients presenting with different stages of the HY.NMSB scale (from 1A to 4D) (n=603).
(a)(b)A worse QoL and a greater disability were associated with a higher H&Y stage. Specifically, the PDQ-39SI and the EUROHIS-QOL8 total score were significantly lower and higher, respectively, in patients with a lower H&Y (Table1 and Figure 2(a)). The ADLS score was higher (indicative of lower disability) in patients with a lower H&Y (Table 1). When patients with a consecutive stage of H&Y were compared, the most significant differences were observed between patients with a stage II of H&Y and those ones with stage III, but no differences were observed between patients with a stage III of H&Y and those ones with stage IV (only 9 patients in this last subgroup) (Table 1). QoL and disability were related to NMS burden as well, so the higher the NMS burden stage, the worse the QoL, and the greater the disability (Table 2 and Figure 2(b)). After classifying participants by combining both scales, H&Y and NMSS (NMSB), QoL and disability were related to the HY.NMSB stage (Figure 2(c)): PDQ-39SI, from 6.7 ± 4.9 (HY.NMSB 1A) to 42.9 ± 11.9 (HY.NMSB 4D) (p<0.0001); EUROHIS-QOL8 total score, from 4.1 ± 0.5 (HY.NMSB 1A) to 3.1 ± 0.6 (HY.NMSB 3D) (p<0.0001; only 1 patient in the stage 4B but with a score of 4.5); and ADLS score, from 94.9 ± 5.7 (HY.NMSB 1A) to 55 ± 19.1 (HY.NMSB 4D) (p<0.0001). With regard to our hypothesis, it was observed that patients with a lower stage of H&Y could have a worse QoL and/or a greater disability if they had a greater NMS burden (Tables 3 and 4). For example, patients with stage I of H&Y and very severe NMS burden (HY.NMSB 1D; n = 15) compared to patients with stage II of H&Y but mild NMS burden (HY.NMSB 2A; n = 101) had a higher PDQ-39SI (28.6 ± 17.1 vs 7.9 ± 5.8; p<0.0001) and a lower PQ-10 (6.4 ± 1.5 vs 7.9 ± 1.2; p<0.0001), EUROHIS-QOL8 (3.5 ± 0.4 vs 4.1 ± 0.4p<0.0001), and ADLS score (88 ± 6.8 vs 91.8 ± 5.9; p=0.025) (Table 3 and Figure 2). Even PDQ-39SI (198 ± 11.9 vs 13.8 ± 9.8; p=0.003) and EUROHIS-QOL8 score (3.6 ± 0.5 vs 3.9 ± 0.5; p=0.030), we are significantly higher and lower, respectively, in those patients with stage I of H&Y and severe NMS burden HY.NMSB 1C; n = 27) than those in ones with stage < II of H&Y and moderate NMS burden (HY.NMS burden 2B; n = 125) (Table 3 and Figure 2). When patients with a stage II of H&Y were compared with those ones with a stage III, a worse QoL was observed in patients with stage II and very severe NMS burden (HY.NMSB 2D; n = 91) than those in patients with a stage III of H&Y but mild NMS burden (HY.NMSB 3A; n = 6) or moderate NMS burden = (HY.NMSB 3B; n = 9): PDQ-39SI 31.8 ± 3.8 vs 14.2 ± 10.9 p=0.003; 31.8 ±13.8 vs. 21.5 ± 7.9 (p=0.029): PQ-10, 6.2 ± 1.6 vs 8.5 ± 1.5 (p=0.003); EUROHIS-QOL8, 3.8 ± 0.6 vs 3.6 ± 0.4 (p=0.048) (Table 4 and Figure 2).Table 1
Quality of life (PDQ-39SI and EUROHIS-QOL8) and disability (ADLS score) in PD patients with regard to Hoehn and Yahr stage (s = 603).
H&Y 1,N = 138H&Y 2,N = 407H&Y 3,N = 49H&Y 4,N = 9papbpcpdPDQ-39SI13.3 ± 12.117.1 ± 12.930.9 ± 15.330.3 ± 15.3<0.00010.037<0.00010.908Mobility10.9 ± 14.216.1 ± 1841.6 ± 23.837.2 ± 24.3<0.00010.036<0.00010.613Activities of Daily Living13.4 ± 14.318.3 ± 18.133.6 ± 2429.1 ± 19.1<0.00010.023<0.00010.604Emotional well-being18.9 ± 16.921.6 ± 20.734.3 ± 21.932.8 ± 13.2<0.00010.372<0.00010.846Stigma12.3 ± 1713.2 ± 19.716.1 ± 22.122.9 ± 32.70.3160.8390.3410.432Social support6.8 ± 14.38.6 ± 16.99.7 ± 19.712.9 ± 22.10.4970.4920.6860.656Cognition14.9 ± 16.420.1 ± 18.127.2 ± 18.931.2 ± 17.9<0.00010.0150.0110.553Communication8.8 ± 13.89.5 ± 14.217.3 ± 19.719.4 ± 17.60.0010.5220.0010.766Pain and discomfort21.1 ± 19.926.9 ± 22.942.5 ± 22.540.7 ± 28.9<0.00010.065<0.00010.835PQ-107.5 ± 1.57.2 ± 6.26.2 ± 2.16.9 ± 1.4<0.00010.234<0.00010.375EUROHIS-QOL83.9 ± 0.53.8 ± 0.53.3 ± 0.63.7 ± 0.5<0.00010.117<0.00010.135Quality of life3.9 ± 0.73.8 ± 0.73.2 ± 0.83.8 ± 0.4<0.00010.207<0.00010.063Health status3.4 ± 0.83.1 ± 0.92.5 ± 0.92.9 ± 0.8<0.00010.012<0.00010.296Energy3.9 ± 0.83.7 ± 0.83.2 ± 0.83.7 ± 1.1<0.00010.195<0.00010.156Autonomy for ADL3.8 ± 0.73.6 ± 0.82.8 ± 0.83.1 ± 0.8<0.00010.023<0.00010.289Self-esteem3.9 ± 0.73.8 ± 0.83.4 ± 0.93.4 ± 0.70.0010.4370.0010.863Social relationships4 ± 0.74.1 ± 0.73.7 ± 0.84 ± 0.90.0210.8900.0040.388Economic capacity3.9 ± 0.73.7 ± 0.83.7 ± 13.9 ± 0.70.4140.8190.1600.546Habitat4.3 ± 0.74.2 ± 0.74.1 ± 0.84.4 ± 0.50.2870.8320.1120.161ADLS score93.5 ± 6.987.8 ± 9.477.1 ± 13.172.5 ± 23.8<0.0001<0.0001<0.00010.416Functional dependency (%)0.78.842.937.5<0.0001<0.0001<0.00010.546Chi-squared, Mann–Whitney–Wilcoxon, and ANOVA test were applied. The results represent percentages or mean±SD;pa, all groups; pb, H&Y 2 vs H&Y 1; pc, H&Y 3 vs H&Y 2; pd, H&Y 4 vs H&Y 3. ADL, Activities of Daily Living; ADLS, Schwab and England Activities of Daily Living Scale; EUROHIS-QOL8, EUROHIS-QOL 8-item index; H&Y, Hoehn and Yahr; PDQ-39SI, 39-item Parkinson’s Disease Quality of Life Questionnaire Summary Index.Figure 2
PDQ-39SI and EUROHIS-QOL8 scores in patients with regard to the H&Y (a), the nonmotor symptoms burden (NMSB) (b), and both (HY.NMSB) (c) (n = 603).
(a)(b)(c)Table 2
Quality of life (PDQ-39SI and EUROHIS-QOL8) and disability (ADLS score) in PD patients with regard to nonmotor symptoms burden: mild (NMS 1-20); moderate (NMS total score 21-40); severe (NMS total score 41-70); very severe (NMS total score > 70).
Mild,N=162Moderate,N=174Severe,N=140Very severe,N=127papbpcpdPDQ-39SI7.7 ± 5.713.8 ± 9.719.9 ± 10.732.9 ± 14.4<0.0001<0.0001<0.0001<0.0001Mobility6.2 ± 11.512.7 ± 15.619.7 ± 15.935.3 ± 22.9<0.0001<0.00010.029<0.0001Activities of Daily Living9.5 ± 11.115.8 ± 15.419.8 ± 16.732.4 ± 23.3<0.0001<0.0001<0.0001<0.0001Emotional well-being9.9 ± 10.815.6 ± 13.926.6 ± 18.741.6 ± 22.6<0.00010.0010.149<0.0001Stigma7.6 ± 14.113.7 ± 18.910.8 ±16.222.9 ± 25.5<0.00010.0250.001<0.0001Social support2.2 ± 8.94.9 ± 12.810.6 ± 17.518.6 ± 21.9<0.0001<0.0001<0.00010.001Cognition7.2 ± 9.616.2 ± 13.924.6 ± 16.234.9 ± 20.1<0.0001<0.00010.036<0.0001Communication3.5 ± 7.38.3 ± 12.411.6 ± 14.719.3 ± 19.7<0.0001<0.0001<0.0001<0.0001Pain and discomfort14.7 ± 15.620.7 ± 18.930.7 ± 19.647.4 ± 24.8<0.00010.002<0.0001<0.0001PQ-107.9 ± 1.27.5 ± 1.46.9 ± 1.46.1 ± 1.7<0.0001<0.00010.003<0.0001EUROHIS-QOL84.1 ± 0.53.9 ± 0.43.6 ± 0.53.3 ± 0.6<0.0001<0.0001<0.0001<0.0001Quality of life4.1 ± 0.53.9 ± 0.63.7 ± 0.73.3 ± 0.8<0.00010.0050.001<0.0001Health status3.5 ± 0.83.3 ± 0.83 ± 0.82.6 ± 0.9<0.00010.0010.006<0.0001Energy4.2 ± 0.73.8 ± 0.73.6 ± 0.83.2 ± 0.9<0.0001<0.00010.004<0.0001Autonomy for ADL4 ± 0.73.8 ± 0.83.4 ± 0.83 ± 0.9<0.00010.001<0.0001<0.0001Self-esteem4.2 ± 0.63.9 ± 0.73.6 ± 0.73.3 ± 0.9<0.00010.010<0.00010.001Social relationships4.4 ± 0.64.1 ± 0.63.9 ± 0.73.6 ± 0.8<0.0001<0.00010.059<0.0001Economic capacity4.1 ± 0.83.9 ± 0.73.8 ± 0.73.5 ± 0.9<0.00010.0790.1800.001Habitat4.4 ± 0.74.3 ± 0.64.2 ± 0.73.9 ± 0.7<0.00010.1050.1230.011ADLS score92.9 ± 6.190.2 ± 8.386.5 ± 10.480.5 ± 12.9<0.00010.001<0.0001<0.0001Functional dependency (%)0.64.611.528.3<0.00010.0240.019<0.0001Table 3
Quality of life (PDQ-39SI and EUROHIS-QOL8) and disability (ADLS score) in patients with stages 1C, 1D, 2A, or 2B of the HY-NMSB scale.
1C,N = 271D,N = 152A,N = 1012B,N = 125papbpcpdPDQ-39SI19.8 ± 11.928.6 ± 17.17.9 ± 5.813.8 ± 9.8<0.0001<0.0001<0.00010.003Mobility18.1 ± 14.927.8 ± 17.76.1 ± 10.513 ± 16.2<0.00010.001<0.00010.035Activities of Daily Living16.5 ± 15.228.3 ± 18.310.9 ± 12.415.9 ± 16.1<0.00010.0070.0560.710Emotional well-being28.7 ± 16.435.5 ± 21.38.9 ± 9.414.9 ± 13.7<0.0001<0.0001<0.0001<0.0001Stigma16.4 ± 20.423.8 ± 23.98.4 ± 15.713.9 ± 19.90.0130.1400.0300.448Social support13.6 ± 17.819.4 ± 22.62.4 ± 9.95.3 ± 13.8<0.00010.003<0.00010.005Cognition21.9 ± 17.432.5 ± 18.88.3 ± 9.615.9 ± 13.7<0.00010.001<0.00010.099Communication14.2 ± 15.920.6 ± 19.64.1 ± 8.47.9 ± 12.1<0.00010.007<0.00010.026Pain and discomfort27.8 ± 20.138.3 ± 27.413.5 ± 13.521.2 ± 20.3<0.00010.010<0.00010.053PQ-106.9 ± 1.66.4 ± 1.57.9 ± 1.27.5 ± 1.5<0.00010.0080.0080.201EUROHIS-QOL83.6 ± 0.53.5 ± 0.44.1 ± 0.43.9 ± 0.5<0.00010.004<0.00010.030Quality of life3.6 ± 0.63.2 ± 0.64.1 ± 0.63.9 ± 0.6<0.0001<0.00010.0010.048Health status3.2 ± 0.93.2 ± 0.63.6 ± 0.73.3 ± 0.80.0140.7260.0510.888Energy3.4 ± 0.73.4 ± 0.64.1 ± 0.63.8 ± 0.7<0.00010.025<0.00010.009Autonomy for ADL3.5 ± 0.73.5 ± 0.54.1 ± 0.63.7 ± 0.7<0.00010.065<0.00010.089Self-esteem3.6 ± 0.83.5 ± 0.64.2 ± 0.63.9 ± 0.7<0.00010.015<0.00010.016Social relationships3.9 ± 0.63.8 ± 0.64.4 ± 0.64.2 ± 0.60.0010.023<0.00010.022Economic capacity3.7 ± 0.73.4 ± 0.73.9 ± 0.83.9 ± 0.60.0100.0250.0140.054Habitat3.9 ± 0.83.9 ± 0.74.4 ± 0.64.3 ± 0.60.0050.0010.1600.114ADLS score92.6 ± 7.188 ± 6.891.8 ± 5.989.5 ± 80.0250.2460.4610.061FD (%)00140.8710.5620.7890.371Chi-squared and Mann–Whitney–Wilcoxon test were applied. The results represent percentages or mean ± SD;pa, 1D vs 2A; pb, 1D vs 2B; pc, 1C vs 2A; pd, 1C vs 2B. ADLS, Schwab and England Activities of Daily Living Scale; EUROHIS-QOL8, EUROHIS-QOL 8-item index; PDQ-39SI, 39-item Parkinson’s Disease Quality of Life Questionnaire Summary Index.Table 4
Quality of life (PDQ-39SI and EUROHIS-QOL8) and disability (ADLS score) in patients with stages 2C, 2D, 3A, or 3B of the HY-NMSB scale.
2C,N = 932D,N = 913A,N = 63B,N = 9papbpcpdPDQ-39SI18.5 ± 10.231.8 ± 13.814.2 ± 10.921.5 ± 7.90.0030.0290.1730.238Mobility17.2 ± 14.932 ± 2.127.1 ± 31.227.5 ± 16.30.3720.7220.7130.048Activities of Daily Living18.4 ± 16.431.1 ± 23.36.9 ± 7.725.9 ± 11.70.0050.7220.0810.084Emotional well-being25.6 ± 20.141.7 ± 23.115.9 ± 20.824.5 ± 19.50.0140.0360.2030.953Stigma9.3 ± 15.122.4 ± 24.47.3 ± 156.9 ± 14.10.1090.0730.6360.749Social support9.9 ± 16.719.1 ± 21.90 ± 02.8 ± 4.20.0150.0480.0810.526Cognition24.4 ± 15.935.7 ± 21.21 ± 2.624.3 ± 13.4<0.00010.109<0.00010.948Communication9.5 ± 13.618.4 ± 18.72.8 ± 6.813.9 ± 13.80.0250.6330.1830.226Pain and discomfort30.9 ± 19.646.1 ± 24.634.7 ± 22.628.7 ± 19.60.2090.0310.8300.673PQ-107 ± 1.46.2 ± 1.68.5 ± 1.57.2 ± 1.30.0030.0690.0250.620EUROHIS-QOL83.7 ± 0.43.3 ± 0.63.8 ± 0.63.6 ± 0.40.0480.1690.5900.377Quality of life3.7 ± 0.73.4 ± 0.74 ± 0.93.6 ± 0.50.1080.5630.4620.328Health status3 ± 0.72.6 ± 0.93.2 ± 0.72.7 ± 0.50.1340.7740.5980.139Energy3.7 ± 0.73.2 ± 0.93.8 ± 0.43.6 ± 0.50.0780.2930.5530.544Autonomy for ADL3.4 ± 0.73 ± 0.93 ± 0.63.2 ± 0.70.8190.6250.1240.340Self-esteem3.6 ± 0.73.2 ± 0.94 ± 0.93.8 ± 0.70.0830.1120.3350.696Social relationships4 ± 0.73.6 ± 0.84 ± 0.73.9 ± 0.60.1150.3220.6490.520Economic capacity3.9 ± 0.73.5 ± 0.94.2 ± 0.73.8 ± 1.10.0640.2310.3110.855Habitat4.3 ± 0.63.9 ± 0.74.2 ± 0.74.1 ± 0.90.3690.2550.7130.751ADLS score86.5 ± 9.381.8 ± 11.590 ± 8.983.3 ± 100.0910.7690.4210.278FD (%)9.725.3022.20.1870.6010.5560.250Chi-squared and Mann–Whitney–Wilcoxon test were applied. The results represent percentages or mean ± SD;pa, 2D vs 3A; pb, 2D vs 3B; pc, 2C vs 3A; pd, 2C vs 3B. ADLS, Schwab and England Activities of Daily Living Scale; EUROHIS-QOL8, EUROHIS-QOL 8-item index; PDQ-39SI, 39-item Parkinson’s Disease Quality of Life Questionnaire Summary Index.Table 5
COPPADIS study group.
Name (last name, first name)LocationRoleContributionAstrid Adarmes, DanielaHospital Universitario Virgen del Rocío, Sevilla, SpainSite investigatorEvaluation of participants and/or data managementAlmeria, MartaHospital Universitari Mutua de Terrassa, Terrassa, Barcelona, SpainSite investigatorNeuropsychologist; evaluation of participantsAlonso Losada, Maria GemaHospital Álvaro Cunqueiro, Complejo Hospitalario Universitario de Vigo (CHUVI), Vigo, SpainSite investigator /PICoordination at the centerEvaluation of participants and/or data managementAlonso Cánovas, AraceliHospital Universitario Ramón y Cajal, Madrid, SpainSite investigatorEvaluation of participants and/or data managementAlonso Frech, FernandoHospital Universitario Clínico San Carlos, Madrid, SpainSite investigatorEvaluation of participants and/or data managementAneiros Díaz, ÁngelComplejo Hospitalario Universitario de Ferrol (CHUF), Ferrol, A Coruña, SpainSite investigator /PICoordination at the centerEvaluation of participants and/or data managementÁlvarez, IgnacioHospital Universitari Mutua de Terrassa, Terrassa, Barcelona, SpainSite investigatorEvaluation of participants and/or data managementÁlvarez Sauco, MaríaHospital General Universitario de Elche, Elche, SpainSite investigator /PICoordination at the centerEvaluation of participants and/or data managementArnáiz, SandraComplejo Asistencial Universitario de Burgos, Burgos, SpainSite investigatorEvaluation of participants and/or data managementArribas, SoniaHospital Universitari Mutua de Terrassa, Terrassa, Barcelona, SpainSite investigatorNeuropsychologist; evaluation of participantsAscunce Vidondo, AranchaComplejo Hospitalario de Navarra, Pamplona, SpainSite investigatorEvaluation of participants and/or data managementAguilar, MiquelHospital Universitari Mutua de Terrassa, Terrassa, Barcelona, SpainSite investigatorEvaluation of participants and/or data managementÁvila Rivera, Maria AsunciónConsorci Sanitari Integral, Hospital General de L´Hospitalet, L´Hospitalet de Llobregat, Barcelona, SpainSite investigator /PICoordination at the centerEvaluation of participants and/or data managementBernardo Lambrich, NoemíHospital de Tortosa Verge de la Cinta (HTVC), Tortosa, Tarragona, SpainSite investigatorEvaluation of participants and/or data managementBejr-Kasem, HelenaHospital de Sant Pau, Barcelona, SpainSite investigatorEvaluation of participants and/or data managementBlázquez Estrada, MartaHospital Universitario Central de Asturias, Oviedo, SpainSite investigatorEvaluation of participantsBotí González, Maria ÁngelesHospital Universitari Mutua de Terrassa, Terrassa, Barcelona, SpainSite investigatorNeuropsychologist; evaluation of participantsBorrué, CarmenHospital Infanta Sofía, Madrid, SpainSite investigator /PICoordination at the centerEvaluation of participants and/or data managementBuongiorno, Maria TeresaHospital Universitari Mutua de Terrassa, Terrassa, Barcelona, SpainSite investigatorNurse study coordinatorCabello González, CarolinaComplejo Hospitalario de Navarra, Pamplona, SpainSite investigatorScheduling of evaluationsCabo López, IriaComplejo Hospitalario Universitario de Pontevedra (CHOP), Pontevedra, SpainSite investigator /PICoordination at the centerEvaluation of participants and/or data managementCaballol, NuriaConsorci Sanitari Integral, Hospital Moisés Broggi, Sant Joan Despí, Barcelona, Spain.Site investigator /PICoordination at the centerEvaluation of participants and/or data managementCámara Lorenzo, AnaHospital Clínic de Barcelona, Barcelona, SpainSite investigatorNurse study coordinatorCarrillo, FátimaHospital Universitario Virgen del Rocío, Sevilla, SpainSite investigatorEvaluation of participants and/or data managementCarrillo Padilla, Francisco JoséHospital Universitario de Canarias, San Cristóbal de la Laguna, Santa Cruz de Tenerife, SpainSite investigator /PICoordination at the centerCasas, ElenaComplejo Asistencial Universitario de Burgos, Burgos, SpainSite investigatorEvaluation of participants and/or data managementCatalán, Maria JoéHospital Universitario Clínico San Carlos, Madrid, SpainSite investigator /PICoordination at the centerEvaluation of participants and/or data managementClavero, PedroComplejo Hospitalario de Navarra, Pamplona, SpainSite investigatorEvaluation of participants and/or data managementCortina Fernández, AComplejo Hospitalario Universitario de Ferrol (CHUF), Ferrol, A Coruña, SpainSite investigatorCoordination of blood extractionsCosgaya, MarinaHospital Clínic de Barcelona, Barcelona, SpainSite investigatorEvaluation of participants and/or data managementCots Foraster, AnnaInstitut d'Assistència Sanitària (IAS) - Instituí Cátala de la Salud. Girona, SpainSite investigatorEvaluation of participants and/or data managementCrespo Cuevas, AneHospital del Mar, Barcelona, Spain.Site investigatorEvaluation of participants and/or data managementCubo, EstherComplejo Asistencial Universitario de Burgos, Burgos, SpainSite investigator /PICoordination at the centerEvaluation of participants and/or data managementDe Deus Fonticoba, TeresaComplejo Hospitalario Universitario de Ferrol (CHUF), Ferrol, A Coruña, SpainSite investigatorNurse study coordinatorEvaluation of participants and/or data managementDe Fábregues, OriolHospital Universitario Vall d´Hebron, Barcelona, SpainSite investigator /PICoordination at the centerEvaluation of participants and/or data managementDíez Fairen, MHospital Universitari Mutua de Terrassa, Terrassa, Barcelona, SpainSite investigatorEvaluation of participants and/or data managementErro, ElenaComplejo Hospitalario de Navarra, Pamplona, SpainSite investigatorEvaluation of participants and/or data managementEscalante, SoniaHospital de Tortosa Verge de la Cinta (HTVC), Tortosa, Tarragona, SpainSite investigator /PICoordination at the centerEvaluation of participants and/or data managementstelrich Peyret, ElenaInstitut d'Assistència Sanitària (IAS) - Instituí Cátala de la Salud. Girona, SpainSite investigatorEvaluation of participants and/or data managementFernández Guillán, NoeliaComplejo Hospitalario Universitario de Ferrol (CHUF), Ferrol, A Coruña, SpainSite investigatorNeuroimaging studiesGámez, PedroComplejo Asistencial Universitario de Burgos, Burgos, SpainSite investigatorEvaluation of participants and/or data managementGallego, MercedesHospital La Princesa, Madrid, SpainSite investigatorEvaluation of participants and/or data managementGarcía Caldentey, JuanCentro Neurológico Oms 42, Palma de Mallorca, SpainSite investigator /PICoordination at the centerEvaluation of participants and/or data managementGarcía Campos, CristinaHospital Universitario Virgen Macarena, Sevilla, SpainSite investigatorEvaluation of participants and/or data managementGarcía Moreno, Jose ManuelHospital Universitario Virgen Macarena, Sevilla, SpainSite investigator /PICoordination at the centerEvaluation of participants and/or data managementGastón, ItziarComplejo Hospitalario de Navarra, Pamplona, SpainSite investigator /PICoordination at the centerEvaluation of participants and/or data managementGuillén Fopiani, DesiréComplejo Hospitalario Universitario de Pontevedra (CHOP), Pontevedra, SpainSite investigatorNeuropsychologist; evaluation of participantsGómez Garre, María del PilarHospital Universitario Virgen del Rocío, Sevilla, SpainSite investigatorGenetic studies coordinationGómez Mayordomo, VíctorHospital Clínico San Carlos, Madrid, SpainSite investigatorEvaluation of participants and/or data managementGonzález Aloy, JavierInstitut d'Assistència Sanitària (IAS) - Instituí Cátala de la Salud. Girona, SpainSite investigatorEvaluation of participants and/or data managementGonzález Aramburu, IsabelHospital Universitario Marqués de Valdecilla, Santander, SpainSite investigatorEvaluation of participants and/or data managementGonzález Ardura, JessicaHospital Universitario Lucus Augusti (HULA), Lugo, SpainSite investigator /PICoordination at the centerEvaluation of participants and/or data managementGonzález García, BeatrizHospital La Princesa, Madrid, SpainSite investigatorNurse study coordinatorGonzález Palmás, Maria JosefaComplejo Hospitalario Universitario de Pontevedra (CHOP), Pontevedra, SpainSite investigatorEvaluation of participants and/or data managementGonzález Toledo, Gabriel RicardoHospital Universitario de Canarias, San Cristóbal de la Laguna, Santa Cruz de Tenerife, SpainSite investigatorEvaluation of participants and/or data managementGolpe Díaz, AnaComplejo Hospitalario Universitario de Ferrol (CHUF), Ferrol, A Coruña, SpainSite investigatorLaboratory analysis coordinationGrau Solá, MireiaConsorci Sanitari Integral, Hospital Moisés Broggi, Sant Joan Despí, Barcelona, SpainSite investigatorEvaluation of participants and/or data managementGuardia, GemmaHospital Universitari Mutua de Terrassa, Terrassa, Barcelona, SpainSite investigatorEvaluation of participants and/or data managementHernández Vara, JorgeHospital Universitario Vall d´Hebron, Barcelona, SpainSite investigator /PICoordination at the centerEvaluation of participants and/or data managementHorta Barba, AndreaHospital de Sant Pau, Barcelona, SpainSite investigatorNeuropsychologist; evaluation of participantsIdoate Calderón, DanielComplejo Hospitalario Universitario de Pontevedra (CHOP), Pontevedra, SpainSite investigaorNeuropsychologist; evaluation of participantsInfante, JonHospital Universitario Marqués de Valdecilla, Santander, SpainSite investigator /PICoordination at the centerEvaluation of participants and/or data managementJesús, SilviaHospital Universitario Virgen del Rocío, Sevilla, SpainSite investigatorEvaluation of participants and/or data managementKulievsky, JaimeHospital de Sant Pau, Barcelona, SpainSite investigator /PICoordination at the centerEvaluation of participants and/or data managementKurtis, MónicaHospital Ruber Internacional, Madrid, SpainSite investigator /PICoordination at the centerEvaluation of participants and/or data managementLabandeira, CarmenHospital Álvaro Cunqueiro, Complejo Hospitalario Universitario de Vigo (CHUVI), Vigo, SpainSite investigatorEvaluation of participants and/or data managementLabrador Espinosa, Miguel ÁngelHospital Universitario Virgen del Rocío, Sevilla, SpainSite investigatorNeuroimaging data analysisLacruz, FranciscoComplejo Hospitalario de Navarra, Pamplona, SpainSite investigatorEvaluation of participants and/or data managementLage Castro, MelvaComplejo Hospitalario Universitario de Pontevedra (CHOP), Pontevedra, SpainSite investigatorEvaluation of participants and/or data managementLegarda, InésHospital Universitario Son Espases, Palma de Mallorca, SpainSite investigator /PICoordination at the centerEvaluation of participants and/or data managementLópez Ariztegui, NuriaComplejo Hospitalario de Toledo, Toledo, SpainSite investigator /PIEvaluation of participants and/or data managementLópez Díaz, Luis ManuelHospital Da Costa de Burela, Lugo, SpainSite investigatorEvaluation of participants and/or data managementLópez Manzanares, LydiaHospital La Princesa, Madrid, SpainSite investigator /PICoordination at the centerEvaluation of participants and/or data managementLópez Seoane, BalbinoComplejo Hospitalario Universitario de Ferrol (CHUF), Ferrol, A Coruña, SpainSite investigatorNeuroimaging studiesLucas del Pozo, SaraHospital Universitario Vall d´Hebron, Barcelona, SpainSite investigatorEvaluation of participants and/or data managementMacías, YolandaFundación Hospital de Alcorcón, Madrid, SpainSite investigatorEvaluation of participants and/or data managementMata, MarinaHospital Infanta Sofía, Madrid, SpainSite investigatorEvaluation of participants and/or data managementMartí Andres, GloriaHospital Universitario Vall d´Hebron, Barcelona, SpainSite investigatorEvaluation of participants and/or data managementMartí, Maria JoséHospital Clínic de Barcelona, Barcelona, SpainSite investigator /PICoordination at the centerEvaluation of participants and/or data managementMartínez Castrillo, Juan CarlosHospital Universitario Ramón y Cajal, Madrid, SpainSite investigator /PICoordination at the centerEvaluation of participants and/or data managementMartinez-Martin, PabloCentro Nacional de Epidemiología y CIBERNED, Instituto de Salud Carlos III. MadridCollaborator in statistical and methods analysisMethods and statistical reviewerMcAfee, DarrianUniversity of Pennsylvania, PhiladelphiaCollaborator in english styleEnglish style reviewerMeitín, Maria TeresaHospital Da Costa de Burela, Lugo, SpainSite investigatorEvaluation of participants and/or data managementMenéndez González, ManuelHospital Universitario Central de Asturias, Oviedo, SpainSite investigator /PICoordination at the centerEvaluation of participants and/or data managementMéndez del Barrio, CarlotaHospital Universitario Virgen del Rocío, Sevilla, SpainSite investigatorEvaluation of participants and/or data managementMir, PabloHospital Universitario Virgen del Rocío, Sevilla, SpainSite investigator /PICoordination at the centerEvaluation of participants and/or data managementMiranda Santiago, JavierComplejo Asistencial Universitario de Burgos, Burgos, SpainSite investigatorEvaluation of participants and/or data managementMorales Casado, Maria IsabelComplejo Hospitalario de Toledo, Toledo, Spain.Site investigatorEvaluation of participants and/or data managementMoreno Diéguez, AntonioComplejo Hospitalario Universitario de Ferrol (CHUF), Ferrol, A Coruña, SpainSite investigatorNeuroimaging studiesNogueira, VíctorHospital Da Costa de Burela, Lugo, SpainSite investigator /PICoordination at the centerEvaluation of participants and/or data managementNovo Amado, AlbaComplejo Hospitalario Universitario de Ferrol (CHUF), Ferrol, A Coruña, SpainSite investigatorNeuroimaging studiesNovo Ponte, SabelaHospital Universitario Puerta de Hierro, Madrid, Spain.Site investigatorEvaluation of participants and/or data managementOrdás, CarlosHospital Rey Juan Carlos, Madrid, Spain, Madrid, Spain.Site investigatorEvaluation of participants and/or data managementPagonabarraga, JavierHospital de Sant Pau, Barcelona, SpainSite investigatorEvaluation of participants and/or data managementIsabel PareésHospital Ruber Internacional, Madrid, SpainSite investigatorEvaluation of participants and/or data managementPascual-Sedano, BertaHospital de Sant Pau, Barcelona, SpainSite investigatorEvaluation of participants and/or data managementPastor, PauHospital Universitari Mutade Terrassa, Terrassa, Barcelona, SpainSite investigatorEvaluation of participants and/or data managementPérez Fuertes, AídaComplejo Hospitalario Universitario de Ferrol (CHUF), Ferrol, A Coruña, SpainSite investigatorBlood analysisPérez Noguera, RafaelHospital Universitario Virgen Macarena, Sevilla, SpainSite investigatorEvaluation of participants and/or data managementPlanas-Ballvé, AnaConsorci Sanitari Integral, Hospital Moisés Broggi, Sant Joan Despí, Barcelona, SpainSite investigatorEvaluation of participants and/or data managementPlanellas, LluísHospital Clínic de Barcelona, Barcelona, SpainSite investigatorEvaluation of participants and/or data managementPrats, Marian ÁngelesInstitut d'Assistència Sanitària (IAS) - Instituí Cátala de la Salud. Girona, SpainSite investigatorEvaluation of participants and/or data managementPrieto Jurczynska, CristinaHospital Rey Juan Carlos, Madrid, Spain, Madrid, SpainSite investigator /PICoordination at the centerEvaluation of participants and/or data managementPuente, VíctorHospital del Mar, Barcelona, SpainSite investigator /PICoordination at the centerEvaluation of participants and/or data managementPueyo Morlans, MercedesHospital Universitario de Canarias, San Cristóbal de la Laguna, Santa Cruz de Tenerife, SpainSite investigatorEvaluation of participants and/or data managementRedondo, NuriaHospital La Princesa, Madrid, SpainSite InvestigatorEvaluation of participants and/or data managementRodríguez Méndez, LuisaComplejo Hospitalario Universitario de Ferrol (CHUF), Ferrol, A Coruña, SpainSite investigatorBlood analysisRodríguez Pérez, Amparo BelénHospital General Universitario de Elche, Elche, SpainSite investigatorEvaluation of participants and/or data managementRoldán, FlorindaHospital Universitario Virgen del Rocío, Sevilla, SpainSite investigatorNeuroimaging studiesRuíz de Arcos, MaríaHospital Universitario Virgen Macarena, Sevilla, Spain.Site investigatorEvaluation of participants and/or data managementRuíz Martínez, JavierHospital Universitario Donostia, San Sebastián, SpainSite investigatorEvaluation of participants and/or data managementSánchez Alonso, PilarHospital Universitario Puerta de Hierro, Madrid, SpainSite investigatorEvaluation of participants and/or data managementSánchez-Carpintero, MacarenaComplejo Hospitalario Universitario de Ferrol (CHUF), Ferrol, A Coruña, SpainSite investigatorNeuroimaging studiesSánchez Díez, GemaHospital Universitario Ramón y Cajal, Madrid, SpainSite investigatorEvaluation of participants and/or data managementSánchez Rodríguez, AntonioHospital Universitario Marqués de Valdecilla, Santander, SpainSite investigatorEvaluation of participants and/or data managementSantacruz, PilarHospital Clínic de Barcelona, Barcelona, SpainSite investigatorEvaluation of participants and/or data managementSantos García, DiegoCHUAC, Complejo Hospitalario Universitario de A CoruñaCoordinator of the ProjectCoordination of the COPPADIS-2015Segundo Rodríguez, José ClementeComplejo Hospitalario de Toledo, Toledo, SpainSite investigatorEvaluation of participants and/or data managementSeijo, ManuelComplejo Hospitalario Universitario de Pontevedra (CHOP), Pontevedra, SpainSite investigator /PICoordination at the centerEvaluation of participants and/or data managementSierra, MaríaHospital Universitario Marqués de Valdecilla, Santander, SpainSite investigatorEvaluation of participants and/or data managementSolano, BertaInstitut d'Assistència Sanitària (IAS) - Instituí Cátala de la Salud. Girona, SpainSite investigator /PICoordination at the centerEvaluation of participants and/or data managementSuárez Castro, EsterComplejo Hospitalario Universitario de Ferrol (CHUF), Ferrol, A Coruña, SpainSite investigatorEvaluation of participants and/or data managementTartari, Juan PabloHospital Universitari Mutua de Terrassa, Terrassa, Barcelona, SpainSite investigatorEvaluation of participants and/or data managementValero, CaridadHospital Arnau de Vilanova, Valencia, SpainSite investigatorEvaluation of participants and/or data managementVargas, LauraHospital Universitario Virgen del Rocío, Sevilla, SpainSite investigatorEvaluation of participants and/or data managementVela, LydiaFundación Hospital de Alcorcón, Madrid, SpainSite investigator /PICoordination at the centerEvaluation of participants and/or data managementVillanueva, ClaraHospital Universitario Clínico San Carlos, Madrid, SpainSite investigatorEvaluation of participants and/or data managementVives, BárbaraHospital Universitario Son Espases, Palma de Mallorca, SpainSite investigatorEvaluation of participants and/or data managementVillar, Maria DoloresHospital Universitario de Canarias, San Cristóbal de la Laguna, Santa Cruz de Tenerife, SpainSite investigatorEvaluation of participants and/or data managementIn a simple linear regression model, the HY.NMSB scale predicted the PDQ-39SI:β = 0.480; CI 95%, 1.981 – 2.661; p<0.0001. After adjustment to other covariates (age, gender, disease duration, levodopa equivalent daily dose, UPDRS-IV, FOGQ, and BDI-II), the HY.NMSB stage contributed significantly to the patient’s QoL (PDQ-39SI as dependent variable) as well: adjusted R-squared 0.591; β = 0.089; CI 95%, 0.098 – 0.770; p=0.011 (Table 2. SM). As compared to the classical H&Y stage alone (not significant in the model), the HY.NMS was multiplied by 12.7 the size effect over the PDQ-39SI (β standardized coefficient of 0.007 for the H&Y in a model with age, gender, disease duration, levodopa equivalent daily dose, UPDRS-IV, FOGQ, BDI-II, and NMSS (p=0.823) vs 0.089 for the HY.NMS in the model with the same covariates included except the NMSS (p=0.011)).


## 4. Discussion

The present study observed that the use in PD patients of a scale that combines the H&Y stage with the NMSS (HY.NMSB) could be useful since it would not only inform about motor and nonmotor aspects but would also serve to know how is the patient’s QoL and autonomy for ADL. This is relevant because many PD patients can be in stages I to III of H&Y for many years and stratification regarding NMS burden providing useful information not only for diagnosis but also for monitoring the outcome and ideally the response to a medication.Ray Chaudhuri et al. [11] proposed a new strategy for clinical classification of PD patients using the NMSS in 5 stratified levels of burden (0 = no NMS; 1 = NMSS, 1-20; 2 = NMSS, 21-40; 3 = NMSS, 41-70; 4 = NMSS > 70) and suggested that this simple assessment could be added to existing motor-based staging (i.e., H & Y) to complement PD assessment and avoid overlooking the weight of the NMS. In 951 PD patients, these authors observed a significant influence of NMS burden on disability and QoL, highlighting the need to include an NMS evaluation for a complete assessment of PD patients. We observed the same in 603 PD patients from the COPPADIS cohort. However, here, we define specifically a scale (HY.NMSB) combining the H&Y stage with the NMS burden: firstly, a number for the H&Y from 1 (stage I) to 4 (stage IV/V); secondly, a letter for the NMS burden from A (non NMS or mild NMS burden; NMSS 0-20) to D (very severe burden; NMSS > 70). Combining the number with the letter, a total of 16 stages are defined, from HY.NMSB 1A (H&Y I and non-NMS/mild NMS burden) to 4D (H&Y IV/V and very severe NMS burden). PD patients without NMS (i.e., NMSS total score = 0) are rare (none in this cohort), but in any case, they are included as “A” because there is really no difference between, for example, a patient with NMSS total score = 0 and another one with NMSS total score = 1 or 3. So, “A” is defined as a patient without NMS or mild NMS burden. On the other hand and with the idea of simplifying the scale, very advanced PD patients with regard to motor stage (H&Y IV and V) are considered together as number 4. After applying this scale (HY.NMSB) for the first time, we observed that QoL and disability were related to H&Y but NMS burden as well, so patients with a lower H&Y but a greater NMS burden can perceive a worse QoL and greater disability than patients with a higher H&Y stage but lower NMS burden. Conventionally, H&Y stages I and II represent mild PD, but this qualification cannot be supported attending the load of NMS and any domain/s they belong. The NMS present in PD may be very variable in number and type, and they maintain only a moderate association with the motor disturbances [10, 11, 19, 20]. In fact, although as expected, patients with mild NMS burden (A; 39.8%) were the most frequent in the group with a stage I of H&Y and patients with very severe NMS burden (D; 44.4%) in the group with H&Y IV/V; more than 30% of the patients in stage I of H&Y had severe or very severe NMS burden. Clinical and neuropathological data are now emerging supporting the concept of the nonmotor dominant endophenotype [21], and it seems necessary in daily practice to know the frequency and the severity of NMS in PD patients, even in early PD patients, because NMS burden could be significant, and this one impacts on their QoL and contributes to disability [7, 9, 15, 22]. Very recently, two PD subtypes have been suggested [23, 24], and it would be of great interest to know if very early PD patients with very severe NMS burden could correspond with the body-first (bottom-up) type and those with mild NMS burden with the brain-first (top-down) type.The application of the HY.NMSB scale could have different uses: (1) a fast and relatively simple way of knowing the motor and nonmotor states of a PD patient, stratifying him/her into a group (diagnosis value; first visit); (2) to monitor the long-term evolution of the patient (prognosis value; follow-up visits); (3) to monitor the response of a patient to a specific therapeutic intervention. In fact, the NMSS total score has been considered as the primary efficacy variable in recent trials [25], and it is known that some NMS can be improved, with dopaminergic medication or nondopaminergic medication [26]. In this context, the HY.NMSB could be used for defining a specific population or as an outcome parameter in clinical trials. For example, nabilone has very recently demonstrated to improve NMS in PD patients in a phase 2 trial [27], being an interesting possibility to identify what patients changed from a superior stage of the HY.NMSB to an inferior stage (e.g., from 2C to 2 B). Finally, the HY-NMSB scale could be useful to indirectly estimate the patient’s perception of QoL and disability. The correlation of H&Y, NMSS, and NMS burden with QoL and disability has been frequently reported [7–9, 22], including in PD patients from the COPPADIS cohort [15, 18], but this is the first time that the relationship considering both motor stage (H&Y) and NMS burden (NMSS) at the same time has been analyzed, and it is important because the influence of NMS burden on QoL perception is critical. An inherent limitation of the proposed classification (HY.NMSB) is the fact that the classification according to NMS is carried out taking into account the total NMS burden but without considering what exactly these symptoms are. Importantly, some NMS could help clinical practitioners to identify patients who are at different stages of the disease, such as hallucinations, fainting, inability to control body sphincters, or believing in unlikely facts [28]. Moreover, and compared with the International Parkinson and Movement Disorder Society─Nonmotor Rating Scale (MDS-NMS) [29], the NMSS collects the patient’s perception about different NMS in the previous 4 weeks but does not about nonmotor fluctuations.A very important limitation is that our sample is not fully representative of the PD population due to inclusion and exclusion criteria (i.e., age limit, no dementia, no severe comorbidities, and no second line therapies) which subsequently entails a bias toward early PD. The majority of the patients from this cohort were in the stage I or II of the H&Y (90.4%), so the same analysis with the proposed classification should be carried out in a cohort with more patients in advanced stages of H&Y. In spite of this and importantly, during the first 5 to 10 years of the disease, many patients with PD will be in stage II of the H&Y, and introducing the NMS burden will help to differentiate the degree of nonmotor affectation, that importantly correlates with QoL perception. In other words, the results of the present study are applicable for a long time to the majority of PD patients, especially in early young PD patients. Second, all scales or questionnaires used for assessing motor and NMS are validated except PQ-10 [8, 15]. Third, NMS were recorded with the NMSS, but specifically, as we commented nonmotor fluctuations were not identified [30]. Fourth, the OFF state (12 hours without taking medication) was considered for defining the H&Y stage because it represents a more natural state of the disease less conditioned by the symptomatic effect of the medication. Moreover, in PD patients with motor fluctuations, the symptoms during the OFF state mostly impact on QoL and autonomy. In any case, previously, similar results applying the HY.NMSB were observed when the H&Y stage was defined during the ON state in 149 PD patients from the CASINO cohort [8, 31]. In the COPPADIS cohort, the results were similar as well when the H&Y was defined during the ON state in those PD patients with motor fluctuations (data not shown). Fifth, the time it took to administer the HY.BMSB scale was not calculated. Finally, this is a cross-sectional study, but the aim of the COPPADIS-2015 study [12] is to follow-up the cohort for 5 years, so changes in HY.NMSB and the relationship with changes in other variables could be analyzed.In conclusion, this is the first time that a specific scale combing the H&Y stage and the NMSS (HY.NMSB scale) is applied in PD patients for knowing the relationship with the patient’s QoL perception and disability regarding the stage. The HY.NMSB scale is simple and reflects the degree of patient involvement more accurately than the H&Y. Patients with a lower H&Y stage may be more affected if they have a greater NMS burden. These results need to be replicated in a larger and well-distributed cohort of patients by motor stage.



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*Source: 8871549-2021-05-15.xml*