Research Article - Neuropsychiatry (2018) Volume 8, Issue 1
Clinical Factors Associated with the Quality Of Life in Patients with Parkinsons disease
- *Corresponding Author:
- Cheng-Hsien Lu
Department of Neurology
Kaohsiung Chang Gung Memorial Hospital
Chang Gung University College of Medicine
No. 123, Ta Pei Road, Niao Sung Hsiang
Kaohsiung City 833, Taiwan
Tel: +886-7-7317123 ext 2283
Abstract
Abstract
Purpose: The purpose of this study was to assess the clinical factors which define the quality of life (QOL) in patients with Parkinson’s disease (PD), and to investigate the relationships between the main contributory factors of the health profile and the overall QOL.
Methods: This prospective study assessed the QOL using the World Health Organization Quality of Life scale brief version (WHOQOL-BREF) Questionnaire. All patients were tested using the Unified Parkinson’s Disease Rating Scale (UPDRS) score, Hoehn and Yahr (HY) stage, Mini-Mental State Examination (MMSE), Schwab and England Activities of Daily Living scale (ADL), Geriatric Depression Scale (GDS), Fatigue Severity Scale (FSS) and the levodopa equivalent dose (LED). Stepwise model of multiple linear regression analysis was used to assess the impact of independent variables on the mean WHOQOL-BREF score.
Results: The mean WHOQOL-BREF score was 11.52 ± 3.94. Total and each domain (physical, psychological, social relationships, and environment domains) WHOQOL-BREF scores were positively correlated with education years, MMSE, and ADL. However, they were negatively correlated with LED; HY stage; UPDRS I, II, and III scores; GDS score; and FSS score (all p<0.0001). Multiple linear regression analysis showed that only UPDRS I and II, GDS, and FSS scores were independently associated with the mean WHOQOL-BREF score.
Conclusion: Based on our results, the impairment of non-motor features including activities of daily living and mentation, behavior, and mood and fatigue (UPDRS I and II, FSS, and GDS) affect the QOL in patients with PD. It is crucial to detect non-motor symptoms in the early phases and prompt treatment, which might help to improve the quality of life.
Keywords
Quality of life; Parkinson’s disease; WHOQOL-BREF
Introduction
Parkinson’s disease (PD) is the second most common neurodegenerative disease, and both motor and non-motor dysfunctions significantly affect the patient’s quality of life (QOL) [1-4]. The QOL means patient-reported outcomes not only included health-related quality of life (HRQOL) but also health status and subjective well-being (SWB) [5]. Therefore, it is important to adequately recognize and assess QOL in patients with PD.
There are different generic and specific instruments to investigate various aspect of QOL in patients with PD [6-11]. Among generic instruments, the Medical Outcomes Study 36- Item Short-Form Health Survey (SF-36) is one of the better known instruments, but it only measures the HRQOL (physical and mental function) [12]. Among specific instruments, the Parkinson’s disease Questionnaire (PDQ-39) and Short Form (PDQ-8) are the commonly tested and used QOL questionnaires for PD, although they do not adequately cover nocturnal sleep, sexuality, and fatigue [13]. To have a fair determination of QOL including not only the HRQOL (physical and psychological health) but also the social and environmental status, the World Health Organization Quality of Life Assessment Short Version (WHOQOL-BREF) questionnaire was designed to measure the overall QOL including personal health, access to health care, social network, and safety of the personal environment [14,15]. The WHOQOL-BREF questionnaire is less mentioned in the research articles about PD, despite being a relatively brief (28-item), cross-culture comparison, available in many language versions including the Taiwan version, and measuring a broad range of perception with life. The WHO defined QOL as an individual’s perception of their position in life in the context of the culture and value systems in which they live, and in relation to their goals, expectations, standard, and concerns [15]. Routine use of the WHOQOL-BREF questionnaire may be more appropriate in measuring the overall QOL in patients with PD, in daily practice.
This hospital-based study aimed to use the cross-culturally valid instrument, the WHOQOL-BREF Taiwan version questionnaire, to analyze the correlation among clinical factors and the overall QOL in patients with PD. This could aid in focused screening and clinical practice for the improvement of the QOL.
Materials and Methods
▪ Study design and participants
This single-center hospital-based prospective study enrolled 119 patients with PD, recruited consecutively from Chang Gung Memorial Hospital-Kaohsiung, a tertiary medical center and the main referral hospital serving a population of 3 million in southern Taiwan.
Patients received a definitive diagnosis of idiopathic PD according to the United Kingdom Parkinson’s Disease Society Brain Bank clinical diagnostic criteria [16] and were followed-up at the Neurology Outpatient Clinic for more than 6 months after titration of their daily doses of anti-Parkinsonian medications to a steady dose in accordance with their clinical symptoms [17]; their ability to correctly express their quality of life was assessed based on the Clinical Dementia Rating (CDR) [18].
Exclusion criteria included the following: (1) newly diagnosed PD or follow-up for less than 6 months as the daily dose of anti- Parkinsonian medications were still under titration; (2) presence of focal neurological signs not related to the diagnostic criteria of PD; (3) impaired consciousness or profound cognitive impairment (CDR score more than or equal to 2). All participants received verbal and written information about the purpose and process of our research which was approved by the hospital’s institutional Review Committees on Human Research.
▪ Clinical data collection
The clinical features included the following: age at disease onset (or age at the time of the first reported symptom attributable to the disease), sex, body height, body weight, body mass index, duration of the disease (time from onset until follow-up), education years, and anti- Parkinsonian medication (levodopa equivalent dose, LED) [19]. An experienced neurology nurse specialist (K.-Y. C) who was blinded to the patients’ clinical and biochemical data was trained to measure these functional scores at the time of enrollment.
All participants underwent brain MRI (Magnetic Resonance Imaging) and 99mTc-TRODAT-1 SPECT imaging for confirmation of the diagnosis [20]. The severity of PD was assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS) [21], and Hoehn and Yahr stage [22]. The UPDRS total score was computed as the sum of UPDRS subscales I, II, and III. All participants were evaluated in the morning when they were in the off phase of the medication cycle. Anti-parkinsonism medications were ceased on the day of the study and resumed after the test. The disability was measured using the Schwab and England (S&E) disability score [23]. The Schwab and England Activities of Daily Living (SEADL) scale is a quantitative tool for evaluating the disability of patients with Parkinson’s disease, ranging from 100% (completely independent, essentially normal) to 0% (bedridden, vegetative function, completely invalid). A higher score means a better functional status and scores below 80% indicate dependency. The depressive symptoms were measured with a 30-item Geriatric Depression Scale (GDS30) [24]. The Geriatric Depression Scale (GDS) consists of 30 questions, each with 2 possible answers scored either 0 or 1, with a maximum score of 30. The severity of depression was classified as follows: no depression (GDS<10) and depression (GDS≥10). Fatigue was measured using the Fatigue Severity Scale (FSS) [25]. The Fatigue Severity Scale (FSS) consists of 9 statements for evaluating the impact of fatigue. The total score was calculated by combining the mean score of each item. A threshold of FSS mean score ≥ 5 was defined as severe fatigue
▪ Neuropsychiatric assessment
The Mini-Mental State Examination (MMSE) was used to assess general intellectual function [26]; the ability to perform digit forward span was also assessed. Clinical Dementia Rating (CDR) scale was used to assess cognitive function, which was indicative of the functional capacity of participants without physical disability [27]. All of the subjects were assigned a CDR rating score as follows: 0 for no dementia and 0.5, 1, 2, and 3 for questionable, mild, moderate, and severe dementia, respectively.
▪ QOL assessment
Participants completed the WHOQOL-BREF questionnaire (Taiwan Version) with answers on a scale of 1 to 5. This is widely used in many countries to assess the QOL of both healthy people and those with disease, and its reliability and validity have been demonstrated [14]. The 28-item questionnaire measures 4 domains: physical health, psychological well-being, social relationships, and environment; and 2 separate items that assess overall QOL and general health satisfaction. The Taiwan version included 2 new national items: being respected/accepted and eating/food [14]. Because the number of items are different for each domain, the mean total score and that of each domain were then multiplied by 4 to allow the total and each domain score to have the same range, from 4 to 20. Higher scores indicate a perceived higher QOL [14].
▪ Outcomes assessments and data analysis
The Cronbach reliability coefficient for all questions on the WHOQOL-BREF questionnaire was 0.96. The coefficients for each of its domains were 0.91 for physical health (domain 1), 0.94 for psychological well-being (domain 2), 0.85 social relationships (domain 3), and 0.79 environment (domain 4). These confirm good internal consistency of the instrument.
Spearman’s rank correlation coefficient was calculated to assess the correlation between the clinical factors and WHOQOL-BREF scores. P-values of less than 0.05 were accepted as significant. Stepwise model of multiple linear regression analysis was used to assess the impact of independent variables on the mean WHOQOL-BREF score. All statistical analyses were conducted using the SAS software package, version 9.1 (2002, SAS Statistical Institute, Cary, North Carolina).
Results
▪ Study patients and their demographic data
The 119 patients with idiopathic PD included 56 males (age range, 32-81 years; mean ± SD, 66.48 ± 1.64 years) and 63 females (age range, 41-82 years; mean ± SD, 66.21 ± 1.25 years) (Table 1). Most (89.1%) of the patients were married, the remaining patients being either single (6.7%), widowed (1.7%) or divorced (1.7%). Mean disease duration was 4.20 ± 3.99 years at the time of enrollment. The mean levodopa equivalent dose was 532.42±519.56 mg/day. The mean education years were 6.81 ± 5.02 and the mean baseline mini-mental status exam score was 23.23 ± 5.78 (Table 1).
| n=119 | |
|---|---|
| Age (years) | 66.34 ± 11.04 |
| Sex (male/female) | 56/63 |
| Body Height (m2) | 158.98 ± 8.01 |
| Body Weight (kg) | 61.13 ± 9.62 |
| Body mass Index (kg/m2) | 24.16 ± 3.43 |
| Disease duration (years) | 4.20 ± 3.99 |
| Education (years) | 6.81 ± 5.02 |
| Striatal dopamine transporter uptake ratios | 1.44 ± 0.20 |
| The levodopa equivalent dose (mg/day) | 532.42 ± 519.56 |
| Unified Parkinson’s Disease Rating Scale | |
| Total UPDRSα | 48.17 ± 28.89 |
| UPDRS Iβ | 4.57 ± 3.24 |
| UPDRS IIγ | 13.87 ± 9.80 |
| UPDRS IIIδ | 31.40 ± 17.35 |
| Hoehn and Yahr stage (n (%)) | |
| Stage I | 37(31%) |
| Stage II | 33(28%) |
| Stage III | 26(21%) |
| Stage IV | 9(8%) |
| Stage V | 14(12%) |
| Geriatric Depression Scale | 13.95 ± 6.08 |
| Mini‐mental state examination score | 23.23 ± 5.78 |
| Schwab and England Activities of Daily Living scale | 74.96 ± 23.47 |
| Fatigue Severity Scale | 5.86 ± 3.12 |
| The World Health Organization Quality of Life scale brief Version (Taiwan Version) | |
| Score of overall quality of life (range from 1 to 4) | 2.67 ± 1.17 |
| Score of overall health (range from 1 to 4) | 2.51 ± 1.01 |
| Score of physical health domain (range from 4 to 20) | 10.54 ± 4.04 |
| Score of psychological domain (range from 4 to 20) | 10.11 ± 4.37 |
| Score of social relationships domain (range from 4 to 20) | 11.94 ± 4.06 |
| Score of environmental domain (range from 4 to 20) | 13.40 ± 3.78 |
| Total WHOQOL score (range from 4 to 20) | 11.52 ± 3.94 |
UPDRS: Unified Parkinson’s Disease Rating Scale
α=“Total UPDRS” score is the combined sum of parts I, II, and III. Theoretical minimum and maximum values are 0 and 176, respectively (176 represents the worst disability and 0 no disability)
β= I. Mentation, behavior, and mood. Theoretical minimum and maximum values are 0 and 16, respectively. (16 represents the worst disability and 0 no disability)
γ= II. Activities of daily living (ADL). Theoretical minimum and maximum values are 0 and 52, respectively. (52 represents the worst disability and 0 no disability)
δ= III. Motor examination. Theoretical minimum and maximum values are 0 and 108, respectively. (108 represents the worst disability and 0 no disability)
Table 1: Basic characteristics of the patients.
The mean total UPDRS score, UPDRS-I (mentation, behavior, and mood) score, UPDRS-II (activities of daily living) score, and UPDRS-III (motor examination) score were 48.17 ± 28.89 (range 5-119). 4.57 ± 3.24 (range 0-14), 13.87± 9.80 (range 1-46), and 31.40 ± 17.35 (range 5-81), respectively. The Hoehn and Yahr staging of the 119 patients with PD were as follows: 37 were stage I, 33 stage II, 26 stage III, 9 stage IV, and 14 Stage V. The mean SEADL, GDS, and FFS scores are listed in Table 1. The mean total WHOQOL-BREF score, overall QOL score, mean overall health score, physical health (domain 1) score, psychological well-being (domain 2) score, social relationships (domain 3) score, and environment (domain 4) score were 11.52 ± 3.94, 2.67 ± 1.17, 2.51 ± 1.01, 10.54 ± 4.04, 10.11 ± 4.37, 11.94 ± 4.06 and 13.40 ± 3.78, respectively (Table 1).
▪ Effects of risk factors on the total score and that of each domain of WHOQOL-BREF
A correlation analysis was used to test the influence of age, disease duration, education years, LED, the striatal 99mTc-TRODAT-1 uptake, HY stage, UPDRS I (Mentation, behavior, and mood) score, UPDRS II (Activities of daily living) score, UPDRS III (Motor examination) score, MMSE, SEADL score, GDS score, and FSS score on the total WHOQOL-BREF score and that of each domain (physical, psychological, social relationships, and environment) (Table 2). Based on the statistical analyses (correlation coefficient, p value), the total WHOQOL-BREF score and that of each domain (physical, psychological, social relationships, and environment) were positively correlated with education years, MMSE, and ADL. However, they were negatively correlated with LED; HY stage; UPDRS I, II, and III scores; GDS score; and FSS score (all p<0.0001) (Table 2).
| Variables | Total Score | Physical | Psychological | Social | Environment | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| r | P value | r | P value | r | P value | r | P value | r | P value | |
| Age | -0.20* | 0.034 | -0.15 | 0.097 | -0.14 | 0.143 | -0.27** | 0.003 | -0.27** | 0.004 |
| Disease Duration | -0.46** | <0.0001 | -0.47** | <0.0001 | -0.39** | <0.0001 | -0.48** | <0.0001 | -0.42** | <0.0001 |
| Education years | 0.34** | <0.0001 | 0.33** | <0.0001 | 0.29** | 0.001 | 0.33** | <0.0001 | 0.44** | <0.0001 |
| LED | -0.42** | <0.0001 | -0.42** | <0.0001 | -0.38** | <0.0001 | -0.37** | <0.0001 | -0.35* | <0.0001 |
| Trodat uptake | 0.28* | 0.027 | 0.22 | 0.077 | 0.25* | 0.043 | 0.27* | 0.031 | 0.25* | 0.042 |
| HY stage | -0.74** | <0.0001 | -0.70** | <0.0001 | -0.69** | <0.0001 | -0.70** | <0.0001 | -0.67** | <0.0001 |
| UPDRS I | -0.73** | <0.0001 | -0.68** | <0.0001 | -0.70** | <0.0001 | -0.66** | <0.0001 | -0.70** | <0.0001 |
| UPDRS II | -0.73** | <0.0001 | -0.72** | <0.0001 | -0.63** | <0.0001 | -0.70** | <0.0001 | -0.66** | <0.0001 |
| UPDRS III | -0.70** | <0.0001 | -0.67** | <0.0001 | -0.63** | <0.0001 | -0.68** | <0.0001 | -0.64** | <0.0001 |
| MMSE | 0.53** | <0.0001 | 0.53** | <0.0001 | 0.54** | <0.0001 | 0.58** | <0.0001 | 0.66** | <0.0001 |
| S&E ADL | 0.73** | <0.0001 | 0.70** | <0.0001 | 0.66** | <0.0001 | 0.71** | <0.0001 | 0.67** | <0.0001 |
| GDS | -0.84** | <0.0001 | -0.78** | <0.0001 | -0.88** | <0.0001 | -0.74** | <0.0001 | -0.73** | <0.0001 |
| FSS | -0.51** | <0.0.001 | -0.49** | <0.0.001 | -0.44** | <0.0.001 | -0.47** | <0.0001 | -0.46** | <0.0001 |
| Overall QoL | 0.90** | <0.0001 | 0.81** | <0.0001 | 0.87** | <0.0001 | 0.79** | <0.0001 | 0.80** | <0.0001 |
| Overall Health | 0.87** | <0.0001 | 0.81** | <0.0001 | 0.86** | <0.0001 | 0.77** | <0.0001 | 0.73** | <0.0001 |
r: correlation coefficient. *indicates that p value <0.05. **indicates that p value <0.0001.
Abbreviations: LED, the levodopa equivalent dose; Trodat uptake, The striatal 99mTc-TRODAT-1 uptake; HY stage, Hoehn and Yahr stage; UPDRS I, Mentation, behavior, and mood; UPDRS II. Activities of daily living (ADL); UPDRS III, Motor examination; MMSE Mini-Mental Status Examination; S&E ADL, Schwab and England Activities of Daily Living; GDS, Geriatric Depression Scale; FSS, Fatigue Severity Scale.
Table 2: Coefficients analysis of the total score and score of each domain of the WHOQOL-BREF questionnaire in patients with Parkinson’s disease.
▪ Clinical factors associated with mean total WHOQOL-BREF score
Variables that were significantly correlated with the total WHOQOL-BREF score were selected in stepwise model of multiple linear regression analysis, and showed that the GDS score (P<0.0001), UPDRS-I score (P=0.019), UPDRS-II score (P<0.0001), and FFS score (p=0.024) were independently associated with the total WHOQOL-BERF score. Stepwise model of multiple linear regression formula was calculated as follows: WHOQOL-BREF total score =17.597-0.185× (GDS)-0.093× (UPDRS II)-0.125× (UPDRS I)-0.148× (FSS) (Table 3).
| F (P value) |
Adjusted R2 |
Regression coefficient | Standard error | P value | |
|---|---|---|---|---|---|
| WHOQOL-BREF (Total score) |
152.83 (P<0.0001) |
0.85 | |||
| Constant | 17.597 | 0.281 | <0.0001 | ||
| GDS | -0.185 | 0.028 | <0.0001 | ||
| UPDRS II | -0.093 | 0.019 | <0.0001 | ||
| UPDRS I | -0.125 | 0.052 | 0.019 | ||
| FSS | -0.148 | 0.065 | 0.024 |
Regression coefficient for each individual variable.
R2 is the proportion of the WHOQOL-BREF variation explained by the model taking into account the listed factors cumulatively.
Abbreviations: WHOQOL-BREF, The World Health Organization Quality of Life scale brief Version; UPDRS II. Activities of daily living (ADL); UPDRS I, Mentation, behavior, and mood; FSS, Fatigue Severity Scale; GDS, Geriatric Depression Scale. This model is controlled for age, sex, education years, disease duration, LED, MMSE and UPDRS III but only significant variables are shown for clear visualization.
Table 3: Effects of the variables on the total score of the WHOQOL-BREF questionnaire in patients with Parkinson’s disease according to correlation analysis.
Discussion
This prospective study evaluated the overall QOL in patients with PD using the WHOQOL-BREF questionnaire and demonstrated two major findings. First, total and each domain (physical, psychological, social relationships and environment) WHOQOL-BREF scores were positively correlated with education years, MMSE and ADL. However, they were negatively correlated with LED; HY stage; UPDRS I, II, and III scores; GDS score; and FSS score (all p<0.0001). One study evaluated QOL in patients with PD using WHOQOLBREF questionnaire, and found a negative correlation between the psychological domain score and disease duration (p = 0.01), as well as the social domain score and disease severity (p = 0.001) [28]. Another study evaluated QOL in patients with PD using the 100-item version of WHOQOL (WHOQOL-100) and found the level of all facets of independence domain, energy and fatigue of physical domain, and three facets of the environment domain were negatively associated with QOL [29]. Second, a stepwise model of multiple linear regression analysis showed that only UPDRS I and II, GDS, and FSS scores were independently associated with the mean WHOQOL-BREF score. Our study demonstrated that non-motor features (UPDRS I and II , GDS, and FSS) have a greater effect on the QOL in patients with PD than do motor features (UPDRS III), and these findings are consistent with those of our previous studies [2,30].
One study demonstrated that depression is a major contributor to the QOL in patients with PD [31], and this conclusion was consistent with that of our previous study and other studies using different QOL instruments (EQ-5D and Medical Outcome Study 36-item short-form Health Survey) [1,2,32,33]. Our recent study also demonstrated that higher mean UPDRS scores (>38.5) are associated with a higher risk of depression which is often unrecognized and untreated. The prevention and evaluation of depressive disorders in the high-risk group are important safety issues and are highly relevant to patients’ QOL [34].
Fatigue, the major non-motor symptom, is one of most debilitating symptoms of PD, and is also associated with other non-motor symptoms (e.g. depression, dementia, and sleep disorders) [35- 38]. Our study demonstrated that the presence of fatigue could affect the QOL in patients with PD. Furthermore, our recent study also showed that a higher mean UPDRS score (>41.5), which may imply an increase in the severity of PD, was associated with a higher risk of fatigue [39].
However, the present study has several limitations. First, as a prospective observational study, it may be subject to the bias of unmeasured factors. Second, these results may not adequately reflect the general populations of PD because we excluded the patients who had severe dementia (CDR equal or more than two) and co-morbidity with other neurological disorders. Second, PD is a slowly progressive neurodegenerative disorder and we did not assess both the effects of dopaminergic therapy and antidepressants, and endurance exercise training. If the changes in function scores, clinical features, and imaging studies followed a standard pattern and temporal relationship, our ability to assess the impact of QOL scale in patients with PD would improve.
Conclusion
Based on our results, routine use of the WHOQOL-BREF questionnaire may be more appropriate into measuring the overall QOL in patients with PD, in daily practice in PD. The impairment of non-motor features including activities of daily living and mentation, behavior, and mood and fatigue (URDRS I and II, FSS and GDS) affect the QOL in patients with PD. It is crucial to detect non-motor symptoms in the early phases and prompt treatment, which might help to improve the quality of life.
Acknowledgements
The authors thank all the subjects who participated in this study.
Competing interests
The authors declare that they have no competing interests.
Ethics approval
The study was approved by Chang Gung Memorial Hospital’s Institutional Review Committee on Human Research.
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