Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.
Biogem Scarl, Ariano Irpino, Italy.
Nat Rev Nephrol. 2020 Aug;16(8):452-469. doi: 10.1038/s41581-020-0266-9. Epub 2020 Mar 31.
Cognitive impairment is an increasingly recognized major cause of chronic disability and is commonly found in patients with chronic kidney disease (CKD). Knowledge of the relationship between kidney dysfunction and impaired cognition may improve our understanding of other forms of cognitive dysfunction. Patients with CKD are at an increased risk (compared with the general population) of both dementia and its prodrome, mild cognitive impairment (MCI), which are characterized by deficits in executive functions, memory and attention. Brain imaging in patients with CKD has revealed damage to white matter in the prefrontal cortex and, in animal models, in the subcortical monoaminergic and cholinergic systems, accompanied by widespread macrovascular and microvascular damage. Unfortunately, current interventions that target cardiovascular risk factors (such as anti-hypertensive drugs, anti-platelet agents and statins) seem to have little or no effect on CKD-associated MCI, suggesting that the accumulation of uraemic neurotoxins may be more important than disturbed haemodynamic factors or lipid metabolism in MCI pathogenesis. Experimental models show that the brain monoaminergic system is susceptible to uraemic neurotoxins and that this system is responsible for the altered sleep pattern commonly observed in patients with CKD. Neural progenitor cells and the glymphatic system, which are important in Alzheimer disease pathogenesis, may also be involved in CKD-associated MCI. More detailed study of CKD-associated MCI is needed to fully understand its clinical relevance, underlying pathophysiology, possible means of early diagnosis and prevention, and whether there may be novel approaches and potential therapies with wider application to this and other forms of cognitive decline.
认知障碍是日益公认的慢性残疾的主要原因，在慢性肾脏病（CKD）患者中很常见。了解肾功能障碍与认知障碍之间的关系可能有助于我们了解其他形式的认知功能障碍。与一般人群相比，CKD 患者患痴呆症及其前驱期（轻度认知障碍，MCI）的风险增加，其特征是执行功能、记忆和注意力缺陷。CKD 患者的大脑成像显示前额皮质的白质损伤，在动物模型中，还显示皮质下单胺能和胆碱能系统受损，同时伴有广泛的大血管和微血管损伤。不幸的是，目前针对心血管危险因素（如抗高血压药物、抗血小板药物和他汀类药物）的干预措施似乎对 CKD 相关的 MCI 几乎没有或没有影响，这表明尿毒症神经毒素的积累可能比血流动力学因素或脂质代谢紊乱在 MCI 发病机制中更为重要。实验模型表明，脑单胺能系统易受尿毒症神经毒素的影响，而该系统负责 CKD 患者常见的睡眠模式改变。在阿尔茨海默病发病机制中起重要作用的神经祖细胞和神经淋巴系统也可能与 CKD 相关的 MCI 有关。需要更详细地研究 CKD 相关的 MCI，以充分了解其临床相关性、潜在的病理生理学、早期诊断和预防的可能方法，以及是否可能有新的方法和潜在的治疗方法，更广泛地应用于这种和其他形式的认知能力下降。
