Review
Pathophysiology of bladder dysfunction in Parkinson's disease

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Abstract

Bladder dysfunction (urinary urgency/frequency) is a common non-motor disorder in Parkinson's disease (PD). In contrast to motor disorders, bladder dysfunction is sometimes non-responsive to levodopa treatment. The brain pathology causing the bladder dysfunction (appearance of overactivity) involves an altered dopamine basal ganglia-frontal circuit, which normally suppresses the micturition reflex. The pathophysiology of the bladder dysfunction in PD differs from that in multiple system atrophy; therefore, it might aid in differential diagnosis. Anticholinergic agents are used to treat bladder dysfunction in PD, although these drugs should be used with caution particularly in elderly patients who have cognitive decline. These treatments might be beneficial in maximizing the patients' quality of life.

Introduction

Parkinson's disease (PD) is a neurodegenerative disorder associated with loss of dopaminergic neurons. The prevalence rate estimates of PD ranged from 65.6 per 100,000 to 12,500 per 100,000. In addition to motor symptoms, patients with PD often show non-motor symptoms. The non-motor problems of PD include neuropsychiatric disorders, sleep disorders, sensory symptoms, and autonomic disorders (Goldstein et al., 2011). Bladder dysfunction is one of the most common autonomic disorders (Jain, 2011, Sakakibara et al., 2008c), the incidence being estimated as 55–80%. Studies have shown that the bladder dysfunction has great significance in relation to quality-of-life measures, early institutionalization, and health economics (McGrother et al., 1990, Sakakibara et al., 2001b). It is particularly important to note that, unlike motor disorder, bladder dysfunction is sometimes non-responsive to levodopa, suggesting that they occur through a complex patho-physiology (Uchiyama et al., 2003). This is because pathology of PD is not confined to the degeneration of dopaminergic neurons in the substantia nigra, and involves other locations in the brain and other neurotransmitter systems than the dopaminergic system. For this reason, add-on therapy is required to maximize patients' quality of life. This article reviews patho-physiology of bladder dysfunction in PD, with particular reference to neural control of the bladder, symptoms, objective assessment, and treatment.

Section snippets

Normal micturition and detrusor overactivity

The lower urinary tract (LUT) consists of two major components, the bladder and urethra. The bladder has abundant muscarinic M2,3 receptors and adrenergic beta 3 receptors, and is innervated by cholinergic (parasympathetic) and noradrenergic (sympathetic) fibers for contraction and relaxation, respectively (de Groat, 2006). The urethra has abundant adrenergic alpha 1A/D receptors and nicotinic receptors, and is innervated by noradrenergic (sympathetic; contraction) and cholinergic (somatic;

Basal ganglia circuit and dopamine

The net effect of the basal ganglia on micturition is thought to be inhibitory (Fig. 2) (de Groat, 2006, Seki et al., 2001, Yoshimura et al., 1998, Yoshimura et al., 2003). Functional neuroimaging during bladder filling results in activation in the globus pallidus of normal volunteers (Nour et al., 2000) and in the putamen in patients with PD (Kitta et al., 2006). In contrast, dopamine transporter imaging was lower in PD patients with urinary dysfunction than in those without it (Sakakibara et

Lower urinary tract symptoms

The reported prevalence of LUT symptoms (LUTS) in patients with PD ranges from 38% to 71% (Andersen, 1985, Berger et al., 1987, Gray et al., 1995, Hald and We, 1982, Hattori et al., 1992, Murnaghan, 1961). However, it has been difficult to determine to what extent PD contributes to LUTS. Men older than 60 years of age may have bladder outlet obstruction due to prostate hyperplasia. Women may have stress urinary incontinence. “Idiopathic DO” (Abrams et al., 2002) may occur in men and women older

Dopaminergic drugs

It is possible that levodopa and other antiparkinson medication may affect bladder function in PD. Aranda and Cramer (1993) studied the effects of 3–8 mg apomorphine injection on the storage function in 2 de novo PD patients, and found that the bladder capacity increased. They gave oral levodopa to one of the patients, and the bladder capacity increased. We compared the frequency of bladder dysfunction in de novo PD and PD with levodopa. In that study, LUTS was less frequent than in the treated

Conclusions

This article reviewed the current concepts of bladder dysfunction in PD. Central nervous system pathology is clearly associated with bladder dysfunction (urinary urgency/frequency) in PD. Anticholinergic agents are the choice to treat bladder dysfunction that does not easily penetrate the BBB. These treatments are beneficial in maximizing patients' quality of life.

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