Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease and is caused by a loss of dopaminergic neurons in the substantia nigra. PD is characterized by the manifestation of motor symptoms such as bradykinesia, static tremor, and rigidity. In addition to motor symptoms, nonmotor symptoms such as hyposmia, sleep disorders, neuropsychiatric symptoms, and autonomic dysfunction become increasingly recognizable over time. These nonmotor symptoms accelerate disease progression and severely affect the patient’s quality of life. Lower urinary tract (LUT) dysfunction is a common nonmotor symptom of PD and was recently reported to occur in 27%–63.9% of PD patients during any stage of their disease [
Micturition is a complicated process controlled by the frontal lobe, basal ganglia, brainstem, spinal cord, and the other central autonomic networks [
From May 2017 to March 2018, this cross-sectional study enrolled 100 PD patients who visited the Department of Neurology at Shengjing Hospital of China Medical University. PD was diagnosed according to the United Kingdom PD Society Brain Bank Clinical Diagnostic Criteria for PD [
All patients were evaluated during the “on” state of PD. A physician specializing in movement disorders collected demographic and clinical data, including the patient’s sex, age, age of onset, disease duration, years of education, levodopa equivalent daily doses (LEDD), LUT symptoms, motor symptoms, and nonmotor symptoms (hyposmia, RBD, constipation, anxiety and depression, and hallucination) during face-to-face interviews. Motor disability and disease severity were rated using the Hoehn–Yahr stage (H-Y stage) [
The overactive bladder symptom score (OABSS) was developed by Homma et al. and has been validated as a simple and effective research tool for assessing an OAB [
Based on the questions of the NMS questionnaire, “If you have loss or change in your ability to taste or smell,” “If you have talking or moving about in your sleep as if you are “acting” out a dream,” “If you have constipation (less than 3 bowel movements a week) or having to strain to pass a stool (faeces),” “If you have feeling anxious, frightened or panicky,” “If you have feeling sad, “low” or “blue,”” and “If you have seeing or hearing things that you know or are told are not there,” the patients who answer “yes,” respectively, are considered accompanying with hyposmia, RBD, constipation, anxiety, depression, and hallucination.
All data were analyzed using the Statistical Package for the Social Sciences (SPSS), Version 17 (Chicago, IL, USA). The Kolmgorow–Smimov test was used to evaluate data for its normal distribution. Data with a normal distribution are presented as the mean ± standard deviation (
Our cohort of PD patients included 55 (55%) males with a mean age of 66.40 ± 9.30 years and 45 (45%) females with a mean age of 65.44 ± 6.81 years. There was no significant difference between the male and female patients in terms of mean age (
Among the 100 participants, 89 (89%) PD patients suffered from LUT symptoms and 45 (45%) PD patients suffered from OAB. Nighttime frequency was the most common LUT symptom with a prevalence of 86%, followed by urgency (50%), urge incontinence (34%), and daytime frequency (17%) (Figure
Frequency of urinary symptoms in PD patients.
The demographic and clinical characteristics of the enrolled PD patients are shown in Table
Demographic and clinical characteristics of the enrolled PD patients and the univariate analysis between PD-OAB and PD-NOAB.
Enrolled PD patients | PD-OAB | PD-NOAB |
|
|
|
---|---|---|---|---|---|
Number of patients | 100 | 45 (45%) | 55 (55%) | ||
Gender (male/female) | 55/45 | 29/16 | 26/29 | 2.949 | 0.086 |
|
65.97 ± 8.247 (range 48–85) | 69.36 ± 7.53 | 63.20 ± 7.82 | −3.982 |
|
|
61.45 ± 8.361 (range 40–81) | 64.30 ± 7.83 | 59.13 ± 8.12 | −3.217 |
|
Disease duration (years) | 4 (2, 7) (range 0.25–20) | 4 (2, 7) | 3.5 (1, 6) | −0.984 | 0.325 |
Education (years) | 9 (9, 12) (range 0–20) | 9 (9, 12) | 10 (9, 12) | −0.774 | 0.439 |
LEDD (mg) | 350 (178.13, 562.50) (range 0–1425) | 337.5 (193.75, 668.75) | 375 (150, 525) | −0.347 | 0.728 |
Motor symptom | |||||
|
2 (2, 3) (range 1–5) | 2.5 (2, 3.5) | 2 (2, 2) | −2.851 |
|
|
35 (27, 47.75) (range 12–112) | 39 (28.5, 56) | 34 (24, 44) | −2.069 |
|
Clinical subtype | |||||
Tremor-dominant (yes/no) | 67/33 | 30/15 | 37/18 | 0.004 | 0.949 |
Akinetic/rigid-dominant (yes/no) | 44/56 | 20/25 | 24/31 | 0.007 | 0.935 |
Nonmotor symptom | |||||
Hyposmia (yes/no) | 39/61 | 19/26 | 20/35 | 0.357 | 0.550 |
|
58/42 | 31/14 | 27/28 | 3.982 |
|
Constipation (yes/no) | 72/28 | 33/12 | 39/16 | 0.072 | 0.788 |
Anxiety and depression (yes/no) | 55/45 | 26/19 | 29/26 | 0.255 | 0.614 |
Hallucination (yes/no) | 11/89 | 6/39 | 5/50 | 0.455 | 0.536 |
MMSE score | 28 (26, 29) (range 11–30) | 27 (25.5, 29) | 28 (26, 29) | −1.454 | 0.146 |
|
24 (21.25, 27) (range 7–30) | 24 (20, 26) | 26 (22, 28) | −2.721 |
|
|
15 (14, 16) (range 6–18) | 14 (12, 15) | 16 (15, 17) | −5.034 |
|
There was no significant difference between the two groups in terms of gender (
The accompanying factors found to be associated with OAB are shown in Table
Risk factors for OAB.
Factor |
|
S.E. | Wald | OR | 95% CI of |
| |
---|---|---|---|---|---|---|---|
Lower | Upper | ||||||
Hoehn–Yahr stage | 1.101 | 0.400 | 7.577 | 3.007 | 1.373 | 6.585 |
|
RBD | 1.228 | 0.535 | 5.264 | 3.414 | 1.196 | 9.745 |
|
FAB score | 1.207 | 0.304 | 15.726 | 3.344 | 1.842 | 6.074 |
|
A multiple linear regression analysis was performed to remove the confounding factors and identify factors that could independently affect storage dysfunction. The results showed that sex (
Multiple linear regression coefficients of OABSS score.
Items |
|
S.E. | 95% CI of |
|
| |
---|---|---|---|---|---|---|
Lower | Upper | |||||
Age (years) | 0.125 | 0.042 | 0.042 | 0.207 | 2.992 |
|
Hoehn–Yahr stage | 1.068 | 0.479 | 0.117 | 2.018 | 2.231 |
|
RBD | 1.553 | 0.608 | 0.347 | 2.759 | 2.556 |
|
FAB score | 1.252 | 0.288 | 0.680 | 1.824 | 4.347 |
|
Constant | −8.644 | 2.518 | −13.643 | −3.646 | −3.433 | 0.001 |
LUT dysfunction in PD has received increasing attention in the recent years due to our increased knowledge of nonmotor symptoms. We found no gender-related differences in the average age, disease duration, and incidence of OAB and LUT dysfunction among the PD patients we recruited, which proves that the data we collected were logical. In our study, the most common LUT symptom in PD patients was nighttime frequency (86%), followed by urgency (50%), urge incontinence (34%), and daytime frequency (17%). The incidence of each of those symptoms was in accordance with those reported in previous studies, and all of them can seriously affect a patient’s quality of life. The most striking finding in our study was that frontal lobe executive impairment, a severe disease stage, and RBD accompanied with a higher prevalence of OAB in PD patients. Furthermore, the severity of LUT disorders in PD patients was independently influenced by the above three factors and also old age.
According to the six pathological stages of Parkinson’s disease proposed by Braak et al. [
Our study used the FAB scale to detect the frontal lobe executive function and found that the FAB scores in the PD-OAB group were significantly lower than those in the PD-NOAB group. We also found that the OABSS was negatively correlated with the FAB score in PD patients, suggesting that the decrease in frontal cortical executive function might be an independent accompanying factor for OAB and could influence the severity of storage symptoms in PD patients. Previous animal studies have demonstrated that the frontal cortex, and especially the prefrontal cortex, plays a significant role in inhibiting the micturition reflex during the storage phase [
When compared with functional neuroimaging, the FAB scale [
A comparative analysis of clinical data for the patients in our study confirmed that the mean H-Y stage of patients in the PD-OAB group was significantly higher than that of patients in the PD-NOAB group and identified the H-Y stage as an accompanying factor for OAB in PD. We also found that increases in the H-Y stage corresponded with increases in the OABSSs, suggesting that the LUT symptoms in PD patients may be closely correlated with nigral dopaminergic depletion. Our findings are in accordance with those reported by Mito et al. [
Previous functional neuroimaging studies revealed a significant decrease of dopamine transporter imaging in the brains of PD patients with urinary dysfunction [
A previous study showed that nigral dopaminergic depletion is related to akinesia/rigidity, but not tremor [
Several specific nonmotor symptoms are also known to be associated with LUT dysfunction [
The pontine micturition center is located on the ventral medial side of the pontine storage center, adjacent to the locus coeruleus, which can project spinal fibers containing excitatory and inhibitory neurotransmitters downward [
The possible correlation between age and the presence of LUT symptoms in PD patients has been previously studied. Some studies reported correlations among them [
Our study did not find any relationship between a patient’s OABSS and sex, disease duration, or education. Previous studies have failed to reach a consensus on this topic [
Our study has limitations. First, this is only a cross-sectional design with no causal inference, and it needs further studies to confirm the results. Secondly, this is a single-center trail with small number of cases. It is better to expand the sample size and design multicenter test for further research. Furthermore, our study lacks information of some other important nonmotor features such as orthostatic hypotension, and further evaluation will be required.
In summary, our study showed that decreased frontal lobe executive function, increased severity of motor disorders, and RBD are independent accompanying factors for OAB. An aggravation of LUT dysfunction in PD patients was consistently associated with the above three factors and also old age. This association may be related to decreased inhibition of the micturition reflex by the superior central nervous system and a neurotransmitter imbalance, which leads to detrusor hyperreflexia. We believe that our research may help to improve the clinical diagnosis and treatment of PD, identify its underlying pathogenesis, and assist in establishing a prognosis for PD patients.
The underlying data related to this study are available from the corresponding author upon request but not for the commercial activities.
The authors declare that they have no conflicts of interest.
The authors wish to thank Yang Xue (Department of Neurology, Shengjing Hospital, Affiliated Hospital of China Medical University, Shen Yang, China) who encourage us all the time and BioMed Proofreading® LLC for careful language revision.
The questionnaire used to define hyposmia, RBD, constipation, anxiety, depression and hallucination.