Haddad R, Panicker J N, Verbakel I, Dhondt K, Ghijselings L, Hervé F, Petrovic M, Whishaw M, Bliwise D L, Everaert K
Department of Urology, NOPIA Research Group, Ghent University Hospital, Ghent, Belgium; GRC 001 GREEN Neuro-Urology Research Group, Sorbonne Université, Rothschild Academic Hospital, AP-HP, 75012 Paris, France.
Department of Uro-Neurology, The National Hospital for Neurology and Neurosurgery and Department of Brain Repair and Rehabilitation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, United Kingdom.
Prog Urol. 2023 Mar;33(4):155-171. doi: 10.1016/j.purol.2023.01.002. Epub 2023 Jan 27.
Aging is associated with a combination of several lower urinary tract (LUT) signs and symptoms, including residual urine, overactive bladder and nocturia. One of the mechanisms of this LUT dysfunction that has not been discussed in dept so far is the role of dopamine (DA).
In this narrative review, we explore the dopaminergic hypothesis in the development of this combination of LUT signs and symptoms in older adults.
DA is one of the neurotransmitters whose regulation and production is disrupted in aging. In synucleinopathies, altered DAergic activity is associated with the occurrence of LUTS and sleep disorders. Projections of DAergic neurons are involved in the regulation of sleep, diuresis, and bladder activity. The low dopamine hypothesis could explain the genesis of a set of LUT signs and symptoms commonly seen in this population, including elevated residual urine, Overactive bladder syndrome and Nocturia (discussed as the RON syndrome). This presentation is however also common in older patients without synucleinopathies or neurological disorders and therefore we hypothesise that altered DAergic activity because of pathological aging, and selective destruction of DAergic neurons, could underpin the presentation of this triad of LUT dysfunction in the older population.
The concept of RON syndrome helps to better understand this common phenotypic presentation in clinical practice, and therefore serves as a useful platform to diagnose and treat LUTS in older adults. Besides recognizing the synucleinopathy "red flag" symptoms, this set of multi-causal LUT signs and symptoms highlights the inevitable need for combination therapy, a challenge in older people with their comorbidities and concomitant medications.
衰老与几种下尿路（LUT）体征和症状相关，包括残余尿、膀胱过度活动症和夜尿症。多巴胺（DA）的作用是迄今为止尚未深入讨论的LUT功能障碍机制之一。
在本叙述性综述中，我们探讨了多巴胺能假说在老年人LUT体征和症状组合发展中的作用。
DA是衰老过程中调节和产生受到破坏的神经递质之一。在突触核蛋白病中，多巴胺能活性改变与LUTS和睡眠障碍的发生有关。多巴胺能神经元的投射参与睡眠、利尿和膀胱活动的调节。低多巴胺假说可以解释该人群中常见的一组LUT体征和症状的发生，包括残余尿增加、膀胱过度活动症和夜尿症（称为RON综合征）。然而，这种表现也常见于没有突触核蛋白病或神经疾病的老年患者中，因此我们假设，由于病理性衰老导致的多巴胺能活性改变以及多巴胺能神经元的选择性破坏，可能是老年人群中这种LUT功能障碍三联征表现的基础。
RON综合征的概念有助于在临床实践中更好地理解这种常见的表型表现，因此是诊断和治疗老年人LUTS的有用平台。除了识别突触核蛋白病的“红旗”症状外，这组多因素导致的LUT体征和症状凸显了联合治疗的必然需求，这对患有合并症和正在服用多种药物的老年人来说是一项挑战。
