慢性腎臟病患者之認知功能障礙及其相關因子探討

過去研究顯示慢性腎臟病(chronic kidney disease, CKD)患者認知功能較一般人差，然而其原因仍然不清楚。已知CKD患者的同胱胺酸濃度會增加，而同胱胺酸是一般族群失智症的危險因子。此外，CKD患者血中尿毒素Indoxyl sulfate (IS)及P-cresol sulfate (PCS)具有對細胞的直接毒性或間接透過增加血管病變，進而造成心血管疾病等併發症。這些尿毒素也可能和CKD患者的腦病變認知功能障礙有關。本研究分為兩個部分，第一部分研究目的包括1) 探討CKD患者的核心認知功能障礙面向；2)探討CKD患者的認知功能表現與血中同胱胺酸濃度及血管危險因子的相關性；第二部分目的為探討CKD患者的認知功能和血中IS及PCS濃度的相關性。本研究為一個案對照研究，納入病患組條件為50歲以上、腎絲球過濾率（Glomerular filtration rate, GFR）＜60 mL/min/1.73 m2之CKD病患。對照組為無腎臟疾病史且腎絲球過濾率≥60 mL/min/1.73 m2之個案。第一部分研究共230位CKD患者及92位對照組，研究結果顯示CKD患者核心認知障礙為記憶力及執行功能障礙。患者血中同胱胺酸濃度越高(β=-0.17, p=0.041)及血管危險因子 (FCRS)分數越高(β=-0.16, p=0.027)，執行功能面向表現越差。第二部分研究共199位CKD患者及84位對照組完成研究，結果顯示患者的血中IS濃度越高，執行功能表現越差(β= -0.18, p=0.021)。上述研究結果顯示CKD患者認知功能障礙和高血中同胱胺酸濃度、高血管危險因子及高血中尿毒素IS有關。然而其他認知功能面向(如記憶障礙)的相關危險因子則在本研究中未發現，由此推估CKD的認知障礙為多重因素造成，未來需要針對其他可能危險因子作進一步研究。

關鍵字

認知功能障礙；慢性腎臟病；同胱胺酸；尿毒素

並列摘要

Patients with chronic kidney disease (CKD) more commonly experience cognitive impairment, but the etiologies are not clear yet. Elevated homocysteine levels are present in CKD, and this is a risk factor for cognitive impairment and vascular diseases in the general population. Uremic toxins such as P-cresol sulfate (PCS) and Indoxyl sulfate (IS) had been proposed to be associated with cardiovascular complications in CKD through direct cell toxic effects or vascular effects. However, the association between IS/PCS and cognitive impairment is unknown. Thus, the first study aimed to 1) investigate the features of cognitive impairment in CKD; 2) investigate the associations of homocysteine level and vascular burden. The second study aimed to investigate the association between IS level and cognitive impairment in patients with CKD. Two hundred and thirty patients with CKD and 92 controls completed the first study. Memory impairment and executive dysfunction were identified as core features of cognitive impairment. Among the patients with CKD, higher serum homocysteine levels (β=-0.17, p=0.041) and higher Framingham Cardiovascular Risk Scale scores (β=-0.16, p=0.027) were correlated with poor executive function independently. In the second study, 199 patients with CKD and 84 controls completed. Higher IS level was correlated with poor executive function (β= -0.18, p=0.021) in patients with CKD. Our results showed that an elevated homocysteine level, an increased vascular burden and higher IS level were associated with executive dysfunction in patients with CKD. Other risk factors related to other cognitive domains in CKD should be investigated in the future.

並列關鍵字

cognitive impairment ； chronic kidney disease ； homocysteine ； uremic toxin

參考文獻

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