Abstract:
Mild cognitive impairment (MCI) is common in people with chronic kidney disease (CKD), and its prevalence increases with progressive loss of kidney function. MCI is characterized by a decline in cognitive performance greater than expected for an individual age and education level but with minimal impairment of instrumental activities of daily living. Deterioration can affect one or several cognitive domains (attention, memory, executive functions, language, and perceptual motor or social cognition). Given the increasing prevalence of kidney disease, more and more people with CKD will also develop MCI causing an enormous disease burden for these individuals, their relatives, and society. However, the underlying pathomechanisms are poorly understood, and current therapies mostly aim at supporting patients in their daily lives. This illustrates the urgent need to elucidate the pathogenesis and potential therapeutic targets and test novel therapies in appropriate preclinical models. Here, we will outline the necessary criteria for experimental modeling of cognitive disorders in CKD. We discuss the use of mice, rats, and zebrafish as model systems and present valuable techniques through which kidney function and cognitive impairment can be assessed in this setting. Our objective is to enable researchers to overcome hurdles and accelerate preclinical research aimed at improving the therapy of people with CKD and MCI.
摘要:
轻度认知障碍(MCI)在慢性肾脏病(CKD)患者中很常见,其患病率随着肾功能的进行性丧失而增加。MCI的特征在于认知表现的下降大于个体年龄和教育水平的预期,但对日常生活的工具活动的损害最小。恶化会影响一个或几个认知领域(注意力,记忆,执行功能,语言,和知觉运动或社会认知)。鉴于肾脏疾病的患病率越来越高,越来越多的CKD患者也会发展为MCI,给这些人带来巨大的疾病负担,他们的亲戚和社会。然而,对潜在的病理机制了解甚少,目前的治疗主要旨在支持患者的日常生活.这说明迫切需要阐明发病机制,和潜在的治疗目标,并在适当的临床前模型中测试新疗法。这里,我们将概述CKD认知障碍实验建模的必要标准。我们讨论了老鼠的使用,大鼠和斑马鱼作为模型系统,并提供了有价值的技术,通过这些技术可以在这种情况下评估肾功能和认知障碍。我们的目标是使研究人员能够克服障碍并加速旨在改善CKD和MCI患者治疗的临床前研究。