Sex variation in the relationship between APOE ε4, cognitive decline, and dementia.

IF 4 Q1 CLINICAL NEUROLOGY

Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Pub Date : 2025-05-02 eCollection Date: 2025-04-01 DOI:10.1002/dad2.70053

Eleanor M Kerr, Jennifer A Ailshire, Eileen Crimmins, Katrina M Walsemann

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引用次数: 0

Abstract

Introduction: We examine if the relationship between apolipoprotein E (APOE) ε4 and cognitive decline and dementia onset differs by sex in non-Hispanic White and Black respondents from the Health and Retirement Study.

Methods: We used race-stratified linear mixed models to estimate cognitive decline and Cox proportional hazards models to estimate time to dementia onset. Sex differences were estimated using interaction terms.

Results: APOE ε4 was associated with cognitive decline (b = -0.4) and dementia onset (hazard ratio [HR] = 1.48) in White adults, and cognitive decline (b = -0.5) in Black adults. The relationship between APOE ε4 and cognitive decline or dementia onset did not differ by sex in either group.

Discussion: Our findings question a key hypothesis in the field-that female APOE ε4 carriers experience faster cognitive decline and earlier dementia onset than their male counterparts-and highlight the importance of using probability samples to reduce survivor and participation bias commonly found in genetics research.

Highlights: White apolipoprotein E ε4 allele (APOE ε4) carriers had faster cognitive decline and earlier dementia onset.Black APOE ε4 carriers had faster cognitive decline.These patterns did not vary by sex for either Black or White adults.

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APOE ε4与认知能力下降和痴呆之间关系的性别差异。

引言：我们研究了载脂蛋白E (APOE) ε4与认知能力下降和痴呆发病之间的关系是否因性别而异。方法：我们使用种族分层线性混合模型来估计认知能力下降，并使用Cox比例风险模型来估计痴呆发病时间。性别差异是通过相互作用来估计的。结果：APOE ε4与白人成人认知能力下降（b = -0.4）和痴呆发病（危险比[HR] = 1.48）相关，与黑人成人认知能力下降（b = -0.5）相关。APOE ε4与认知能力下降或痴呆发病的关系在两组中均无性别差异。讨论：我们的研究结果质疑了该领域的一个关键假设，即女性APOE ε4携带者比男性患者认知能力下降更快，痴呆发病更早，并强调了使用概率样本来减少遗传学研究中常见的幸存者和参与偏见的重要性。重点：白色载脂蛋白E ε4等位基因（APOE ε4）携带者认知能力下降较快，痴呆发病早。黑色APOE ε4携带者认知能力下降较快。这些模式在黑人和白人成年人中都没有性别差异。

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

Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Medicine-Psychiatry and Mental Health

CiteScore

7.80

自引率

7.50%

发文量

101

审稿时长

8 weeks

期刊介绍： Alzheimer''s & Dementia: Diagnosis, Assessment & Disease Monitoring (DADM) is an open access, peer-reviewed, journal from the Alzheimer''s Association® that will publish new research that reports the discovery, development and validation of instruments, technologies, algorithms, and innovative processes. Papers will cover a range of topics interested in the early and accurate detection of individuals with memory complaints and/or among asymptomatic individuals at elevated risk for various forms of memory disorders. The expectation for published papers will be to translate fundamental knowledge about the neurobiology of the disease into practical reports that describe both the conceptual and methodological aspects of the submitted scientific inquiry. Published topics will explore the development of biomarkers, surrogate markers, and conceptual/methodological challenges. Publication priority will be given to papers that 1) describe putative surrogate markers that accurately track disease progression, 2) biomarkers that fulfill international regulatory requirements, 3) reports from large, well-characterized population-based cohorts that comprise the heterogeneity and diversity of asymptomatic individuals and 4) algorithmic development that considers multi-marker arrays (e.g., integrated-omics, genetics, biofluids, imaging, etc.) and advanced computational analytics and technologies.