Tsuruya Kazuhiko, Yoshida Hisako
Contrib Nephrol. 2018;196:27-36. doi: 10.1159/000485694. Epub 2018 Jul 24.
There is an increasing prevalence of dementia associated with population aging, and anti-dementia measures have now become of increasing importance in Japan. Chronic kidney disease (CKD) is a risk factor for cognitive impairment.
We previously demonstrated that hemodialysis patients have a higher prevalence of brain atrophy, even at younger age, than the general population, and also demonstrated the association between frontal lobe atrophy and frequency of rapid decline in blood pressure during the hemodialysis session. Recently, we demonstrated that decline in gray matter volume in CKD patients on peritoneal dialysis was significantly more rapid compared to non-dialysis-dependent CKD patients, and also showed a close association between gray matter atrophy and executive dysfunction in CKD patients, suggesting the importance of preventing brain atrophy for the prevention of cognitive impairment. Our recent epidemiological study demonstrated that both decreased kidney function and albuminuria were identified as independent risk factors for the development of dementia. In addition, it has been reported that possible contributing factors include anemia, oxidative stress, and the renin-angiotensin system (RAS). Previous reports have demonstrated that CKD patients with severe anemia show cognitive impairment, which was recovered by correction of anemia using erythropoiesis-stimulating agents. Then, we examined the role of oxidative stress and RAS using a mouse model of CKD-associated cognitive impairment, and demonstrated that the RAS inhibitor candesartan, as well as the antioxidant tempol, inhibited the development of cognitive impairment through inhibition of oxidative stress in the hippocampus. Key Messages: In CKD patients, progression of brain atrophy is more rapid and cognitive impairment is more common than in non-CKD subjects. Oxidative stress and RAS in the brain are associated with CKD-associated cognitive impairment.
随着人口老龄化，痴呆症的患病率日益增加，抗痴呆措施在日本变得越来越重要。慢性肾脏病（CKD）是认知障碍的一个危险因素。
我们之前证明，即使在较年轻的年龄段，血液透析患者脑萎缩的患病率也高于普通人群，并且还证明了额叶萎缩与血液透析期间血压快速下降频率之间的关联。最近，我们证明，与非透析依赖的CKD患者相比，腹膜透析的CKD患者灰质体积下降明显更快，并且还表明CKD患者的灰质萎缩与执行功能障碍密切相关，这表明预防脑萎缩对于预防认知障碍很重要。我们最近的流行病学研究表明，肾功能下降和蛋白尿均被确定为痴呆症发生的独立危险因素。此外，据报道，可能的促成因素包括贫血、氧化应激和肾素 - 血管紧张素系统（RAS）。先前的报告表明，患有严重贫血的CKD患者表现出认知障碍，使用促红细胞生成素刺激剂纠正贫血后这种障碍得以恢复。然后，我们使用CKD相关认知障碍的小鼠模型研究了氧化应激和RAS的作用，并证明RAS抑制剂坎地沙坦以及抗氧化剂Tempol通过抑制海马体中的氧化应激来抑制认知障碍的发展。关键信息：在CKD患者中，脑萎缩的进展比非CKD受试者更快，认知障碍也更常见。大脑中的氧化应激和RAS与CKD相关的认知障碍有关。
