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克隆性造血的不定潜能与慢性肾脏病患者认知障碍风险降低有关。

Clonal hematopoiesis of indeterminate potential is associated with reduced risk of cognitive impairment in patients with chronic kidney disease.

机构信息

Division of Nephrology, Department of Medicine, University of Illinois Chicago, Chicago, Illinois, USA.

Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Palo Alto, California, USA.

出版信息

Alzheimers Dement. 2024 Oct;20(10):6960-6971. doi: 10.1002/alz.14182. Epub 2024 Aug 8.

Abstract

INTRODUCTION

Clonal hematopoiesis of indeterminate potential (CHIP) and dementia disproportionately burden patients with chronic kidney disease (CKD). The association between CHIP and cognitive impairment in CKD patients is unknown.

METHODS

We conducted time-to-event analyses in up to 1452 older adults with CKD from the Chronic Renal Insufficiency Cohort who underwent CHIP gene sequencing. Cognition was assessed using four validated tests in up to 6 years mean follow-up time. Incident cognitive impairment was defined as a test score one standard deviation below the baseline mean.

RESULTS

Compared to non-carriers, CHIP carriers were markedly less likely to experience impairment in attention (adjusted hazard ratio [HR] [95% confidence interval {CI}] = 0.44 [0.26, 0.76], p = 0.003) and executive function (adjusted HR [95% CI] = 0.60 [0.37, 0.97], p = 0.04). There were no significant associations between CHIP and impairment in global cognition or verbal memory.

DISCUSSION

CHIP was associated with lower risks of impairment in attention and executive function among CKD patients.

HIGHLIGHTS

Our study is the first to examine the role of CHIP in cognitive decline in CKD. CHIP markedly decreased the risk of impairment in attention and executive function. CHIP was not associated with impairment in global cognition or verbal memory.

摘要

简介

不确定潜能的克隆性造血(CHIP)和痴呆症不成比例地给患有慢性肾脏病(CKD)的患者带来负担。CHIP 与 CKD 患者认知障碍之间的关联尚不清楚。

方法

我们对接受 CHIP 基因测序的慢性肾功能不全队列中多达 1452 名年龄较大的 CKD 患者进行了事件时间分析。在长达 6 年的平均随访时间内,使用四项经过验证的测试评估认知能力。认知障碍的定义为测试得分比基线平均值低一个标准差。

结果

与非携带者相比,CHIP 携带者发生注意力障碍的可能性明显降低(校正后的危险比[HR] [95%置信区间{CI}] = 0.44 [0.26, 0.76],p = 0.003)和执行功能障碍(校正后的 HR [95% CI] = 0.60 [0.37, 0.97],p = 0.04)。CHIP 与全球认知或言语记忆障碍之间没有显著关联。

讨论

CHIP 与 CKD 患者注意力和执行功能障碍的风险降低有关。

重点

我们的研究首次检验了 CHIP 在 CKD 认知下降中的作用。CHIP 显著降低了注意力和执行功能障碍的风险。CHIP 与全球认知或言语记忆障碍无关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f02d/11485087/759c003f8929/ALZ-20-6960-g002.jpg

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