Parkinson disease (PD) is a common progressive neurodegenerative disease, found in approximately 1% of the population aged 60 years and above and becomes more common with age [1, 2]. Internationally, the prevalence of the disease has doubled in the last 25 years, while disability and death due to PD are increasing at a faster rate than for any other neurological disorder [3].

PD is characterised by a triad of hallmark motor symptoms: bradykinesia, rigidity, and resting tremor—resulting from progressive loss of midbrain dopaminergic neurons in the substantia nigra pars compacta and the presence of Lewy bodies in surviving neurons [4]. In addition to motor symptoms, PD involves an array of nonmotor symptoms, including autonomic dysregulation and cognitive dysfunction [5]. The autonomic dysregulation can lead to neurogenic lower urinary tract dysfunction, orthostatic hypotension, dysphagia, sialorrhea, gastroparesis, constipation, and sexual dysfunction [6].

Cognitive dysfunction in PD may range from subjective cognitive impairment, to mild cognitive impairment, to dementia [4].

Lower urinary tract symptoms (LUTS) are prevalent in up to 85% of persons living with PD [7]. LUTS encompasses storage, voiding, and obstructive symptoms [8]. Urinary dysfunction in PD has a major impact on patients’ quality of life (QoL) [9].

Urinary storage symptoms in PD often occur as part of a neurogenic overactive bladder (OAB) syndrome, a manifestation of neuronal dysregulation, which is characterised by increased urinary urgency, urinary frequency, nocturia, and urinary urge incontinence (UUI) [9].

Urinary voiding symptoms in PD often occur because of several different pathophysiological processes. These include neurogenic underactive bladder (UAB), external sphincter or bladder neck dyssynergia, and bladder outflow obstruction (BOO) resulting from benign or malignant prostatic enlargement. UAB encompasses difficulty emptying the bladder (causing elevated postvoid residual volume), sensations of inadequate bladder emptying (causing elevated or normal postvoid residual volumes), hesitancy or intermittent urinary stream, reduced strength of urinary stream, and a need to strain to maintain adequate micturition [8]. Detrusor underactivity is defined as reduced strength and duration of contraction of the detrusor muscle, resulting in prolonged or inadequate bladder emptying [10]. Subjects may simultaneously experience both OAB and UAB symptoms, a syndrome named coexisting overactive-underactive bladder [11]. Obstructive and voiding symptoms overlap considerably.

LUTS can be assessed quickly and effectively in PD using validated questionnaires and clinical rating scales that query symptom severity. Among the most commonly used questionnaires are the International Prostate Symptom Score, the Danish Prostate Symptom Score (Dan-PSS), and the International Consultation on Incontinence Questionnaires (ICIQ) for men (ICIQ-MLUTS) and women (ICIQ-FLUTS) [9, 12].

In a study launched by a task force established by the Movement Disorder Society (MDS) to review questionnaires and clinical rating scales for the assessment of urinary symptoms in PD, the ICIQ-MLUTS (formerly ICS Male SF), OAB-questionnaire short form, and ICIQ-OABqol were the only 3 questionnaires found to satisfy all tested clinimetric properties of clinical scales used in urological disorders (excluding “minimal clinically important difference”). The ICIQ-MLUTS and ICIQ-FLUTS are highly detailed questionnaires that assess storage, voiding, and incontinence symptoms. The reliability of most questionnaire items was found to be “excellent” and met the criteria of “recommended with caveats” for use in PD (caveat: recommendation of further validation in PD) [12]. To our knowledge, there are currently no studies that have used these detailed, validated questionnaires to assess LUTS in a cohort of PD patients. In this unique study, we employed the ICIQ-MLUTS and ICIQ-FLUTS to assess urinary symptoms.

The relationship between LUTS, motor, and cognitive function have been previously investigated. However, there are few studies that utilise the Montreal Cognitive Assessment (MoCA) to score cognitive performance in PD and explore its association with motor symptoms and LUTS severity. Moreover, a paucity of data exists on how these relationships differ between non–drug-naive and drug-naive PD (DNPD). Winge et al. [13] suggest that LUTS scores (measured with Dan-PSS) correlate with age and Hoehn and Yahr stage of disease. They further found a significant correlation between LUTS scores and disease severity (measured with Unified Parkinson Disease Rating Scale, UPDRS). In a similar study by Xu et al. [14], the OAB symptom scores were compared against the Hoehn and Yahr stage and MDS-UPDRS score: patients with OAB symptoms were aged older, at a more advanced stage of disease, and had more severe symptoms – including cognitive dysfunction. Although the literature generally agrees that there is a correlation between increased motor symptoms severity, worsening LUTS, and worsening cognitive performance, it remains to be discovered if poor cognitive performance can predict current or prospective worsening of LUTS.

This study aims to assess LUTS, motor, and cognitive function and correlations using validated clinical questionnaires (ICIQ-MLUTS, ICIQ-FLUTS, UPDRS – Motor Examination [UPDRS-ME], modified Hoehn and Yahr, MoCA) in patients diagnosed with PD as well as determining whether these relationships differ between non–drug-naive and drug-naive PD.

18 patients with confirmed PD were assessed for differences in sociodemographic and health characteristics, and comparisons were made between non–drug-naive versus drug-naive PD (Table 2), and between male versus female sex (Table 3).

PD group had similar median LUTS scores (13.5% PD vs. 11.5% DNPD), higher median bother scores (9.9% PD vs. 3.1% DNPD), higher median stage of functional disability (as shown by Hoehn and Yahr stage: stage 3 PD vs. stage 2 DNPD), higher median motor symptoms scores (33 PD vs. 28 DNPD), and similar median MoCA scores (24/30 PD vs. 24/30 DNPD). Only the difference in disease duration between non–drug-naive and drug-naive PD met the threshold for statistical significance set (P<0.050) (Table 2).

Women had a higher median disease duration (6 years female vs. 2 years male), higher median LUTS scores (37.5% females vs. 11.5% males), higher median bother scores (29.2% female vs. 3.8% male), higher median stage of functional disability (as shown by Hoehn and Yahr stage: stage 4 females vs. stage 2 males), similar median motor symptoms scores (33 females vs. 30 males), and similar median MoCA scores (23 of 30 females vs. 24 of 30 males). Despite these differences, none met the significance threshold set (P<0.050) (Table 3).

Urinary incontinence symptoms scores were significantly correlated with worse QoL scores due to LUTS (r=0.76, P<0.001), with total urinary symptoms scores (r=0.82, P<0.001), and negatively correlated with MoCA scores (r=-0.52, P=0.046). No such correlation was found between urinary incontinence symptoms and motor symptoms severity scores (r=0.09, P=0.725) (Table 4).

Fig. 2 illustrates the correlation between urinary incontinence symptoms and MoCA scores (r=-0.52, P=0.046). Fig. 3 demonstrates a linear relationship between increasing LUTS severity and bother scores (r=0.76, P<0.001). An increase in LUTS severity is associated with a proportional increase in impact of QoL.

Cognitive impairment was found to be associated with urinary incontinence symptoms. No such statistically significant correlation was found between urinary incontinence symptoms and motor symptoms. Additionally, urinary incontinence symptoms were most significantly and strongly correlated with overall LUTS severity, compared to urinary storage, filling, or voiding symptoms. This suggests that cognitive function may be a better predictor of functional urinary disability in PD patients than their motor symptoms severity.

The highly detailed, validated questionnaires (ICIQ-MLUTS, ICIQ-FLUTS, MoCA, UPDRS-ME, modified Hoehn and Yahr stage) were used to assess the baseline LUTS, motor, and cognitive function and correlations of both non–drug-naive and drug-naive PD. This is the first study of its kind to demonstrate a statistically significant correlation between urinary incontinence and cognitive impairment using these questionnaires.

Longer duration of disease was significantly correlated with more severe motor symptoms and higher stages of functional motor disability. This was an expected finding and reflected in similar studies, such as by Winge et al. [13].

Non–drug-naive PD patients were found to have more severe motor symptoms, more severe LUTS, higher reported bother scores, and similar cognitive performance compared to their drug-naive counterparts. None of these findings met this study’s threshold for statistical significance. There were twice as many PD (n=12, 66.7%) as drug-naive PD patients (n=6, 33.3%). Such a ratio is likely due to the temporal nature of recruiting a drug-naive patient: there is a small recruitment window following diagnosis and before pharmacological therapy. By comparison, the recruitment timeframe is not inherently restricted in non–drug-naive patients. Interestingly, cognitive performance was observed to be very similar across all participants, supporting existing evidence that mild cognitive impairment is prevalent in many non–drug-naive and even already in drug-naive patients by time of diagnosis [4, 16].

There were fewer women (n=3, 16.7%) compared to men (n=15, 83.3%) in this study as may be expected owing to the known higher prevalence of PD in men compared to women. Female subjects were older, lived with increased disease duration, had worse LUTS and higher levels of functional disability, and similar cognitive performance. Although this pattern of more severe, symptom-driven phenotype though reduced prevalence of disease is expected in women [5, 17], there were too few female subjects to reliably interpret this comparison.

Episodes of urinary urgency, UUI, and detrusor overactivity (DO) on urodynamics have been shown to be more common in patients with DLB than in patients with PD without DLB (93%, 53%, and 92% in patients with DLB vs. 53%, 27%, and 46% in patients with PD but without DLB) [18]. Furthermore, urinary urgency episodes, urge incontinence, and DO are also more common in patients with PD without DLB compared to those with Alzheimer dementia [18]. The onset of UUI in patients with PD and DLB occurs earlier (3.2 years) and before severe cognitive impairment when compared to patients with Alzheimer’s dementia where UI tends to occur after 6.5 years and after severe cognitive decline.

The origin of bladder dysfunction in PD has several possible origins. These include non-relaxation of the urethral sphincter leading to BOO and secondary DO [19]. It is now more commonly believed that DO develops following loss of substantia nigra cells as the basal ganglia exert an inhibitory action on the micturition reflex [19]. The severity of bladder symptoms has been shown to correlate with the level of degeneration of the caudate nucleus on imaging studies [13]. It is likely that urinary symptoms in PD are also related to cortical dysfunction and an associated difficulty in processing sensory information [20, 21]. The cerebral cortex’s role in processing afferent signals from the bladder may explain the more severe urinary symptoms in patients with DLB as well as those in our study.

Given the increased prevalence of PD in men and with age, older male patients with PD LUTS are very likely to have coexisting benign prostatic enlargement and obstruction. On urodynamic testing, men with PD are often found to have coexisting neurogenic DO and BOO. Urologists often face a dilemma regarding whether to offer BOO surgery to men with BOO and PD. In the study of Staskin et al. [22] published in 1988, the rates of urinary incontinence in patients with PD who underwent transurethral resection of the prostate (TURP), increased from 17% before TURP to 28% after. It is likely however that this study included patients with multisystem atrophy as well as PD which may account for the high rates of urinary incontinence observed. In a later study by Roth et al. [23] published in 2009, where patients were more stringently selected, 64% of men who were in urinary retention before BOO surgery were catheter-free after, continence was restored in 5 out of 10 men, and there was no new urinary incontinence at 3 years followup. There remains nevertheless a dilemma in such patients as although, BOO surgery may mean a catheter is not needed, urinary urgency in a patient with impaired mobility can often lead to UUI. Urologists therefore often pay close attention to the motor function of PD patients when considering the appropriateness of BOO surgery. This study would suggest that the cognitive function should also be taken into account as poor cognitive function may represent a marker of worse outcomes.

Limitations of this study include the relatively small total study population, especially of DNPD patients.

In conclusion, cognitive impairment in patients with PD appears to be more strongly associated with urinary incontinence severity than motor symptoms. When considering the appropriateness of urological intervention in PD patients, cognitive function should be taken into account as well as motor function.