Clonal Hematopoiesis of Indeterminate Potential Associated with Covert Cerebral Changes.

IF 8.1 1区医学 Q1 CLINICAL NEUROLOGY

Annals of Neurology Pub Date : 2025-06-27 DOI:10.1002/ana.27304

Yijuan Li, Dingding Zhang, Fei Han, Lixin Zhou, Jun Ni, Ming Yao, Zhengyu Jin, Shuyang Zhang, Liying Cui, Xinzhuang Yang, Yi-Cheng Zhu

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Abstract

Objective: Clonal hematopoiesis of indeterminate potential (CHIP) is an emerging risk factor for cardio-cerebrovascular diseases. This study aimed to investigate CHIP's association with cerebrovascular or glymphatic changes in a community-based population.

Methods: This study examined Chinese community cohort participants. CHIP mutations were identified through whole-exome sequencing. Intracranial arterial stenosis, silent brain infarcts, cerebral small vessel disease markers, and diffusion along the perivascular space index were identified by magnetic resonance imaging. The correlation between CHIP and neuroimaging outcomes was investigated through univariate and multivariate logistic/linear regression. The multivariate regression model was adjusted for cerebrovascular disease risk factors, including age, sex, body mass index, smoking status, hypertension, diabetes, and hyperlipidemia.

Results: In total, 18.2% (224 out of 1,229) participants were identified as carriers of CHIP mutations. The prevalence of CHIP generally increases with age (p = 0.009). After adjusting for vascular risk factors using multivariate regression, CHIP mutations were found to be significantly associated with increased odds of large magnetic resonance imaging-defined infarcts (>15 mm; OR 3.20; 95% CI 1.18 to 8.43; p = 0.018), inversely associated with diffusion along the perivascular space (β = -0.02; 95% CI -0.04 to 0; p = 0.034), and showed a borderline association with intracranial arterial stenosis (OR 1.52; 95% CI 0.99 to 2.30; p = 0.053). Notably, no statistically significant correlations were observed between CHIP and cerebral small vessel disease markers or brain atrophy measures.

Interpretation: CHIP was significantly associated with glymphatic dysfunction and large infarcts, and marginally associated with intracranial arterial stenosis. Further research is needed to elucidate the pathophysiology linking CHIP to cerebral covert changes. ANN NEUROL 2025.

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不确定电位的克隆造血与隐性脑改变相关。

目的：不确定电位克隆造血（CHIP）是一种新出现的心脑血管疾病危险因素。本研究旨在调查CHIP与社区人群脑血管或淋巴改变的关系。方法：本研究以华人社区队列为研究对象。通过全外显子组测序鉴定CHIP突变。磁共振成像发现颅内动脉狭窄、无症状性脑梗死、脑小血管疾病标志物和沿血管周围空间扩散指数。通过单变量和多变量logistic/线性回归研究CHIP与神经影像学结果的相关性。多因素回归模型调整了脑血管疾病危险因素，包括年龄、性别、体重指数、吸烟状况、高血压、糖尿病和高脂血症。结果：总共有18.2%（1229名参与者中的224名）被确定为CHIP突变携带者。CHIP的患病率一般随年龄增长而增加（p = 0.009）。在使用多变量回归对血管危险因素进行调整后，CHIP突变被发现与磁共振成像定义的大面积梗死的几率增加显著相关(bb0 15 mm；或3.20;95% CI 1.18 ~ 8.43；P = 0.018)，与沿血管周围空间扩散呈负相关(β = -0.02；95% CI -0.04 ~ 0；p = 0.034)，并与颅内动脉狭窄呈边缘性相关(OR 1.52；95% CI 0.99 ~ 2.30；p = 0.053)。值得注意的是，CHIP与脑血管疾病标志物或脑萎缩指标之间没有统计学上显著的相关性。解释：CHIP与淋巴功能障碍和大面积梗死显著相关，与颅内动脉狭窄轻微相关。需要进一步的研究来阐明CHIP与大脑隐性变化之间的病理生理学联系。Ann neurol 2025。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Annals of Neurology 医学-临床神经学

CiteScore

18.00

自引率

1.80%

发文量

270

审稿时长

3-8 weeks

期刊介绍： Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.