Parkinson’s disease (PD) is a chronic degenerative disease of the central nervous system that evolves slowly and progressively and is characterized by bradykinesia, muscle rigidity and resting tremor among other motor signs and symptoms[1],[2]. Quality of life is significantly impaired not only by motor symptoms, but also by non-motor symptoms such as depression, anxiety, pain, constipation, hyposmia and sleep disturbances[3],[4].
There are few studies on the incidence and prevalence of PD in Brazil; however, the most recent study shows that the disease affects 3.3% of Brazilians over the age of 60 years[4]. One of the concerns when treating PD patients is to improve their quality of life. This includes their physical, functional and emotional well-being, their degree of independence and their family relationships, as well as social, economic and political aspects of their lives[5],[6].
A decline in quality of life in individuals with PD has been associated with worsening motor symptoms and the combination of neurodegenerative phenomena, psychological suffering and stigma associated with the disease[7]. However, in-depth studies are required to differentiate between the impact of PD at different stages of the disease[6],[7].
The objective of this study was to investigate which factors are associated with clinical/functional decline and a decline in quality of life in individuals with mild and moderate PD.
METHODS
The study was a cross-sectional one, and data on individuals who had been diagnosed with PD, and were registered at the Paraná Association for Individuals with Parkinson’s Disease (APPP), were collected from January to May 2012 in the city of Curitiba, in the state of Paraná, Brazil. The convenience sample comprised 100 individuals of both sexes between the ages of 60 and 80 years with impairment rated between 1 and 3 on the Hoehn and Yahr (HY) scale. The group with mild PD (MIG), consisting of 50 individuals classified as HY 1-2, was compared with the group with moderate PD (MOG), which consisted of 50 individuals classified as HY 3[8],[9]. The demographic data are shown in [Table 1].
Table 1
Comparison of mild Parkinson’s disease and moderate Parkinson’s disease groups in terms of gender, age, race, marital status and level of education.
Variable
|
Mild
|
Moderate
|
p-value*
|
|
|
n (%)
|
n (%)
|
Gender
|
|
|
|
Female
|
28 (56)
|
22 (44)
|
|
Male
|
22 (44)
|
28 (56)
|
0.317
|
Age (years)
|
|
|
|
60-65
|
11 (22)
|
13 (26)
|
|
66-70
|
16 (32)
|
8 (16)
|
|
71-75
|
10 (20)
|
17 (34)
|
|
76-80
|
13 (26)
|
12 (24)
|
0.196
|
Race
|
|
|
|
White
|
45 (90)
|
46 (92)
|
|
Yellow/Black
|
5 (10)
|
4 (8)
|
1
|
Marital status
|
|
|
|
Married
|
32 (64)
|
38 (76)
|
|
Separated/widow(er)/single
|
18 (36)
|
12 (24)
|
0.275
|
Level of education
|
|
|
|
Primary education (incomplete)
|
9 (18)
|
11 (22)
|
|
Primary education (complete)
|
27 (54)
|
19 (38)
|
|
High school (complete or incomplete)
|
5 (10)
|
8 (16)
|
|
Third-level education (complete or incomplete)
|
9 (18)
|
12 (24)
|
0.438
|
p* < 0.05.
Individuals were only included in the study if they agreed to take part, signed a voluntary informed-consent form and were present on the days when the data were collected. Individuals with dementia or any other concomitant neurodegenerative disease were excluded. The study started after it had been approved by the Human Research Ethics Committee of the Hospital de Clínicas, Federal University of Paraná (ref. no. 2654.261/2011-11).
The evaluation protocol covered clinical history and demographic, clinical, functional and quality-of-life data. The demographic data were collected in the interview, and the clinical history was obtained from the patients’ medical records. Clinical/functional data were obtained by applying the Unified Parkinson’s Disease Rating Scale (UPDRS) (activities of daily living [ADL] and motor examination sections)[9]. Quality-of-life data were collected with the Parkinson’s Disease Questionnaire (PDQ-39)[10]. The UPDRS and PDQ-39 were filled out by the researcher.
The UPDRS evaluates an individual’s signs, symptoms and activities based on self-reports and clinical observation and consists of 42 questions in four sections. The ADL and motor examination sections were analyzed.
The PDQ-39 is an easily-applied, widely-used questionnaire on quality of life in individuals with PD, which evaluates the individual’s health in the previous month. The 39 multiple choice questions cover eight domains and have five possible answers: never, occasionally, sometimes, often and always[11],[12]. The questionnaire is normally filled out by the individual. However, it was decided to complete it with the help of the researcher during a one-to-one interview because of the possibility of some of the respondents having a limited education or difficulty writing due to the motor symptoms of the disease.
Information on HY staging was obtained from the patients’ medical records at APPP. The influences of age, gender, education, marital status and disease duration on quality of life and ADL and motor examination scores were also examined.
Statistics
Quantitative variables were described in terms of their mean, median, minimum, maximum and standard deviation, and qualitative variables in terms of frequency and percentage. The non-parametric Mann-Whitney test was used to compare the two groups (MIG and MOG) based on the UPDRS and PDQ-39 scores.
Spearman’s coefficient was used to evaluate the correlation between the UPDRS and PDQ-39 scores and HY staging and between the UPDRS and the PDQ-39 scores. The significance level was set at p < 0.05. The data were analyzed with Statistica 8.0.
RESULTS
The mean disease duration in the MIG was 3.4 (± 2.2) years and 8.1 (± 4.7) in the MOG. The MOG had greater impairment in the ADL domain (UPDRS). This finding had borderline significance and was particularly noticeable in the increased drooling (p < 0.004), greater need for assistance with personal hygiene (p = 0.02) and increased frequency of freezing (p = 0.042) in this group. Although greater impairment was observed in motor examination items in the MOG, this was not statistically significant (p = 0.220). Nevertheless, when each item in this domain was considered individually, significant differences were observed in resting tremor (p < 0.035), pill-rolling (p < 0.001) and bradykinesia (p < 0.031) ([Table 2]).
Table 2
Comparison of the mild Parkinson’s disease group with the moderate Parkinson’s disease group in the activities of daily living and motor-examination sections of the UPDRS items with a statistically significant difference.
UPDRS – ADLs
|
Stage
|
Number of individuals and % for each answer
|
p-value*
|
|
0
|
1
|
2
|
3 or 4
|
Drooling
|
Mild
|
24 (48)
|
15 (30)
|
11 (22)
|
0 (0)
|
|
Moderate
|
9 (18)
|
18 (36)
|
19 (38)
|
4 (8)
|
0.004*
|
Personal hygiene
|
Mild
|
5 (10)
|
34 (68)
|
10 (20)
|
1 (2)
|
|
Moderate
|
0 (0)
|
38 (76)
|
6 (12)
|
6 (12)
|
0.020*
|
Freezing
|
Mild
|
7 (14)
|
23 (46)
|
12 (24)
|
8 (16)
|
|
Moderate
|
8 (16)
|
11 (22)
|
13 (26)
|
18 (36)
|
0.042*
|
UPDRS - Motor examination
|
Resting tremor
|
Mild
|
5 (10)
|
30 (60)
|
12 (24)
|
3 (6)
|
|
Moderate
|
1 (2)
|
33 (66)
|
6 (12)
|
10 (20)
|
0.035*
|
Pill-rolling
|
Mild
|
25 (50)
|
23 (46)
|
2 (4)
|
0 (0)
|
|
Moderate
|
7 (14)
|
39 (78)
|
3 (6)
|
1 (2)
|
0.001**
|
Bradykinesia
|
Mild
|
3 (6)
|
21 (42)
|
1 (2)
|
25 (50)
|
|
Moderate
|
1 (2)
|
32 (64)
|
4 (8)
|
13 (26)
|
0.031*
|
UPDRS: Unified Parkinson’s Disease Rating Scale. ADLs: Activities of Daily living. Categories 2, 3 and 4 were combined for the statistical analysis. Motor Examination: Categories 3 and 4 were combined for the statistical analysis. *Chi-square test, p < 0.05.
In the evaluation of quality of life as measured by the PDQ-39, the means of seven of the eight items analyzed were greater in the MOG than in the MIG. These differences were statistically significant in the mobility (p < 0.013), stigma (p < 0.043) and cognition (p < 0.002) domains ([Table 3]). The difference in the bodily discomfort domain between the groups was not statistically significant, but individual analysis of the items showed that painful muscle cramps and spasms caused significantly more impairment of quality of life in the MOG group (p = 0.04). The answers to the PDQ-39 for which there was a statistically significant difference between the two groups are shown in [Table 4].
Table 3
Comparison of quality-of-life scores in the Parkinson’s Disease Questionnaire-39 domains for the mild, and moderate Parkinson’s disease groups.
Domain
|
Stage
|
n
|
Mean
|
Median
|
Minimum
|
Maximum
|
Standard deviation
|
p-value*
|
Mobility
|
Mild
|
50
|
19.2
|
20.0
|
1.0
|
37.0
|
7.5
|
|
Moderate
|
50
|
23.4
|
23.0
|
10.0
|
38.0
|
7.1
|
0.013*
|
ADLs
|
Mild
|
50
|
9.4
|
9.0
|
0.0
|
19.0
|
4.6
|
|
Moderate
|
50
|
11.6
|
11.0
|
2.0
|
24.0
|
4.8
|
0.050
|
Well-being
|
Mild
|
50
|
10.0
|
12.0
|
0.0
|
26.0
|
5.1
|
|
Moderate
|
50
|
10.5
|
11.0
|
1.0
|
18.0
|
4.4
|
0.724
|
Stigma
|
Mild
|
50
|
2.7
|
1.5
|
0.0
|
12.0
|
3.1
|
|
Moderate
|
50
|
3.9
|
2.0
|
0.0
|
18.0
|
3.8
|
0.043*
|
Support
|
Mild
|
50
|
6.7
|
8.0
|
1.0
|
12.0
|
2.3
|
|
Moderate
|
50
|
7.4
|
8.0
|
2.0
|
11.0
|
2.1
|
0.089
|
Cognition
|
Mild
|
50
|
5.8
|
7.0
|
0.0
|
12.0
|
2.6
|
|
Moderate
|
49
|
7.3
|
8.0
|
2.0
|
12.0
|
2.4
|
0.002*
|
Communication
|
Mild
|
50
|
3.3
|
3.5
|
0.0
|
8.0
|
2.6
|
|
Moderate
|
50
|
3.6
|
4.0
|
0.0
|
8.0
|
2.4
|
0.614
|
Bodily discomfort
|
Mild
|
50
|
6.3
|
7.0
|
0.0
|
11.0
|
2.3
|
|
Moderate
|
50
|
6.2
|
6.0
|
2.0
|
10.0
|
1.8
|
0.525
|
ADLs: Activities of Daily living; *Statistically significant difference in the non-parametric Mann-Whitney test at a significance level of p < 0.05.
Table 4
Answers in the PDQ-39 domains with statistically significant, or borderline statistically significant differences between the mild, and moderate Parkinson’s disease groups.
PDQ-39 domains
|
Difference between the MIG and MOG groups
|
Mobility
|
Q1. Have you had difficulty doing the leisure activities you like?
|
p = 0.041
|
Q10. Have you been confined to the house more than you would like?
|
p = 0.052
|
ADLs domain
|
Q5. Have you had difficulty cutting up your food?
|
p = 0.048
|
Q6. Have you had difficulty holding a drink without spilling it?
|
p = 0.043
|
Emotional well-being domain
|
Q5. Have you felt anxious?
|
p = 0.01
|
Q6. Have you felt worried about your future? (p=0.054)
|
p = 0.054
|
Stigma domain
|
Q2. Have you avoided situations which involve eating or drinking in public?
|
p = 0.045
|
Cognition domain
|
Q2. Have you had problems with your concentration?
|
p = 0.018
|
Q3. Have you felt your memory was bad?
|
p = 0.027
|
Bodily discomfort domain
|
Q1. Have you had painful muscle cramps or spasms?
|
p = 0.04
|
MIG: group with mild PD; MOG: group with moderate PD; PDQ-39: Parkinson’s disease questionnaire-39.
There was no correlation between gender and clinical/functional status or quality of life in individuals in the MIG. In the MOG, a decline in quality of life was associated with a lack of support from friends and family members (p = 0.01).
Among married individuals, a decline in quality of life was associated with stigma (p = 0.02) in the MOG and with a lack of support from friends and family members in both groups (p < 0.001).
There was no correlation between age and clinical/functional status or quality of life in individuals in the MIG. In the MOG, increasing age was associated with greater dependence in ADLs (p = 0.02) and greater cognitive impairment (concentration and memory, p = 0.01).
Greater disease duration was associated with a decline in quality of life in the ADL (MIG, p = 0.03) and emotional well-being (MOG, p = 0.01) domains ([Table 5]).
Table 5
Relation between UPDRS and PDQ-39 domains and disease duration in the mild, and moderate Parkinson’s disease groups.
Variable
|
Mild
|
Moderate
|
|
|
r
|
p-value
|
r
|
p-value
|
ADLs
|
0.14
|
0.328
|
0.17
|
0.230
|
UPDRS
|
Motor examination
|
-0.03
|
0.811
|
0.17
|
0.232
|
Mobility
|
-0.05
|
0.742
|
0.19
|
0.188
|
ADLs
|
0.30
|
0.035*
|
0.11
|
0.459
|
Well-being
|
0.01
|
0.948
|
0.34
|
0.017*
|
PDQ-39
|
Stigma
|
0.12
|
0.414
|
-0.05
|
0.729
|
Support
|
-0.13
|
0.387
|
0.01
|
0.972
|
Cognition
|
0.15
|
0.311
|
0.27
|
0.060
|
Communication
|
0.06
|
0.681
|
0.24
|
0.087
|
Bodily discomfort
|
0.16
|
0.275
|
0.07
|
0.629
|
ADLs: activities of daily living; UPDRS: unified Parkinson’s disease rating scale. PDQ-39: Parkinson’s disease questionnaire-39.
DISCUSSION
The domain that evaluates independence in ADLs was significantly more affected in patients with moderate PD. This finding corroborates the results reported in the literature, in which mild PD is characterized by complete functionality and moderate PD by functional impairment due to the more severe signs and symptoms, which act as precursors of disability[13],[14].
Detailed analysis of the responses in this domain showed that the need for assistance with personal hygiene together with drooling and more frequent freezing were markers of loss of independence and difficulty living with embarrassment and limited social interaction. Drooling is associated with muscle rigidity and bradykinesia, symptoms that also lead to a greater need for assistance with personal hygiene[15]. For Khoo et al.[16], non-motor signs such as drooling were common in the early stages of PD and may adversely affect patients’ functional status and well-being.
A sudden loss of the ability to start or sustain a specific motor activity (freezing) can also adversely affect performance in ADLs and subject the individual to more frequent falls[17].
While there was no significant difference between the mild and moderate PD groups in the motor examination section of the UPDRS as a whole, analysis of each item showed that there was a significant difference in resting tremor, pill-rolling and bradykinesia between the groups. Bradykinesia, or slowness of movement, directly affects performance of activities such as turning in bed, standing up, getting dressed and walking[2],[15]. It can be inferred from the results of the ADL section that the ability to perform activities related to personal hygiene is also affected.
Resting tremor, which is usually the first sign reported by individuals with PD[15],[16],[17],[18], was identified as the sign most closely associated with perceived worsening of the patient’s health. Santos, Menezes and Souza[19] reported that individuals in their series experienced embarrassment, particularly in connection with tremor because of its association with alcoholism. In addition to embarrassment, symptoms such as tremor and pill-rolling evolve in parallel with prejudice and reduced self-esteem and self-image, as they lead to shame, anxiety, a risk of depression, shyness in public spaces and social isolation[19].
Akinetic-rigid syndrome generally manifests when there has already been a 60% to 80% loss in dopaminergic neurons in the substantia nigra. Here, these symptoms were more important in individuals in the MOG, who had a mean disease duration of eight years, compared with three years in the MIG[17],[20].
The greatest impairment in terms of quality of life in the MOG was observed in the domains of mobility, stigma, cognition and ADLs, corroborating the findings of studies by Navarro-Peternella et al.,[9] Pinheiro et al.,[13] Navarro-Peternella and Marcon[14], and Quintella et al.[21]
In the mobility domain, having difficulty doing pleasurable leisure activities was one factor that adversely affected quality of life, a finding also reported in studies by Mandira[22] and Tavares et al.[23]. Normal mobility is required to perform ADLs and leisure activities; reduced mobility compromises performance of these activities, limits the activities that can be performed and increases the time required to perform them. Individuals in the MOG also reported that they were confined to the home more than they would like, indicating that they are increasingly less able to perform activities outside their homes. Increasing physical impairment associated with the main symptoms of the disease causes individuals with PD to become isolated, while at the same time making them more dependent on others to perform activities that previously gave them a sense of personal satisfaction, in turn further reducing their quality of life[13],[24].
A greater dependence on others to carry out daily activities such as cutting food and drinking without spilling was a further factor in the decline in quality of life in these patients, particularly when the disease was in the moderate stage. Rigidity, bradykinesia and tremor impose limitations on these activities[15], which in turn leads to irritability, anxiety, insecurity and pessimism as the individual is faced with the prospect of increasing dependence on others[24].
Anxiety and concern about the future were significantly more important in the MOG, corroborating the study by Correia et al.[20], showing that depressive symptoms, including anxiety, contribute to a decline in quality of life in these individuals. Navarro-Peternella and Marcon[14] studied individuals with PD and found that fear and insecurity about dependence on others, about loss of independence at work and in ADLs and about the future in general, help to aggravate the condition. The individuals in their study reported that understanding the unstable nature of the disease and the fact that it was incurable is something that sadly they have to face for the rest of their lives and that will be part of their relationships and day-to-day activities.
More individuals in the MOG than the MIG reported avoiding situations that involved eating or drinking in public. This difference was statistically significant. Stigma in the MOG was an important social factor that adversely affected quality of life in the individuals assessed. Werle et al.[25] investigated quality of life in individuals with cervical dystonia, a chronic disease that is also associated with stigma. They found that the need to hide the disease, insecurity in the presence of new people, problems with friends and family members, fear about the disease and sadness and irritation were factors that reduced their quality of life.
In our sample, problems related to concentration and poor memory were more significant in the MOG and progressively impaired quality of life, corroborating the study by Rodríguez-Violante et al.[26] Motor symptoms are no longer considered the only important determinants of quality of life in individuals with PD, and the importance of non-motor symptoms, such as depression, apathy, fatigue, pain and cognitive deterioration, have been increasingly recognized[9],[17].
Here, the groups were similar in terms of gender, and the decline in quality of life among men was related to lack of support from friends and family members, corroborating the study by Navarro-Peternella and Marcon[9]. In a study by Tavares et al.,[23] the domain that evaluated social relations was a predictor of decline in quality of life in men with PD.
Quality of life among married individuals in our series was worse in the social support domain in both the mild and moderate stages. Among married individuals with moderate PD, greater impairment of quality of life was also associated with stigma. This finding is unexpected as married individuals are normally considered to have greater support and acceptance. On the other hand, this finding may be explained by the fact that a chronic disease that causes increasing dependence can be a source of conflict and strengthen or weaken affective ties and family bonds[14],[27].
While in the present study older age among individuals in the moderate stage was related to worse scores for ADLs and cognition in the PDQ-39, in a study by Tedrus et al.,[28] the greatest impairment was observed for the ADL and mobility domains. Longer disease duration was associated with greater impairment of quality of life in the ADL and emotional well-being domains in the PDQ-39, a finding also reported in other studies[26],[29]. In the study by Tedrus et al.,[28] a decline in quality of life in individuals with PD was associated not only with disease duration but also with advanced age and age of onset.
In conclusion, markers of decline in quality of life in the moderate stage of PD were related to stigma, worsening cognition, greater mobility impairment and reduced independence in ADLs. Drooling, a greater need for assistance with personal hygiene and a greater frequency of freezing caused significant quality-of-life impairment in individuals in the moderate stage of the disease together with resting tremor, pill-rolling and bradykinesia.