妇女健康主动记忆研究中潜力不确定的克隆造血和认知障碍的风险

IF 11.1 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's & Dementia Pub Date : 2025-09-30 DOI:10.1002/alz.70737

Yasminka A. Jakubek, Aaron P. Smith, Xiaoyan I. Leng, Megan E. Hall, Daniel Ezzat, Yash Pershad, Jason M. Collins, Md Mesbah Uddin, David W. Fardo, Pradeep Natarajan, Alexander G. Bick, Jacob O. Kitzman, Michael C. Honigberg, Kathleen M. Hayden, JoAnn E. Manson, Siddhartha Jaiswal, Eric A. Whitsel, Alexander P. Reiner

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引用次数: 0

摘要

不确定潜力克隆造血（CHIP）会增加几种慢性衰老相关疾病的风险。矛盾的是，在最近的研究中，CHIP与较低的痴呆风险有关。方法：我们在妇女健康倡议记忆研究中研究了基线CHIP与轻度认知障碍（MCI）和/或可能的痴呆之间的关系。采用基于血液的靶向测序检测CHIP。Cox比例风险模型检查了认知障碍发生的时间，调整了传统的风险因素。结果：使用传统的变异等位基因分数（VAF）阈值为2%，CHIP与偶发认知障碍无关。较大CHIP克隆（VAF≥8%）的存在与判定可能痴呆的发生率较低相关（风险比= 0.62[95%可信区间= 0.41 ~ 0.94],p = 0.025），而与复合结局MCI/可能痴呆的相关性较弱且重叠1.0。讨论：CHIP与绝经后妇女认知障碍风险降低的关联可能取决于VAF和损害严重程度。亮点：WHIMS包括约5000名绝经后妇女，随访长达25年。CHIP与WHIMS中判定可能痴呆的风险降低相关。大型CHIP克隆（> 8% VAF），但不是小型克隆(

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Clonal hematopoiesis of indeterminate potential and the risk of cognitive impairment in the Women's Health Initiative Memory Study

INTRODUCTION

Clonal hematopoiesis of indeterminate potential (CHIP) confers an increased risk of several chronic aging-related diseases. Paradoxically, CHIP was associated with lower risk of dementia in recent studies.

METHODS

We examined associations between baseline CHIP and incident mild cognitive impairment (MCI) and/or probable dementia in the Women's Health Initiative Memory Study. CHIP was detected using blood-based targeted sequencing. Cox proportional hazards models examined time to onset of cognitive impairment, adjusting for traditional risk factors.

RESULTS

Using a conventional variant allele fraction (VAF) threshold of 2%, CHIP was not associated with incident cognitive impairment. The presence of larger CHIP clone (VAF ≥ 8%) was associated with a lower incidence of adjudicated probable dementia (hazard ratio = 0.62 [95% confidence interval = 0.41 to 0.94], p = 0.025), while the association with the composite outcome MCI/probable dementia was weaker and overlapped 1.0.

DISCUSSION

The association of CHIP with lower risk of cognitive impairment in postmenopausal women may be dependent on VAF and impairment severity.

Highlights

The WHIMS comprises ∼5000 postmenopausal women, followed for up to 25 years.
CHIP was associated with reduced risk of adjudicated probable dementia in WHIMS.
Large CHIP clones (> 8% VAF), but not small clones (<8% VAF), showed an association.
CHIP was not associated with MCI in the WHIMS cohort.

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来源期刊

Alzheimer's & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

期刊介绍： Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.