Prospective associations of interleukin-6 and APOE allele with cognitive decline in biracial community-dwelling older adults: The Chicago Health and Aging Project (CHAP).

IF 4 Q1 CLINICAL NEUROLOGY

Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Pub Date : 2024-10-21 eCollection Date: 2024-10-01 DOI:10.1002/dad2.70002

Ted K S Ng, Todd Beck, Pankaja Desai, Klodian Dhana, Robert S Wilson, Denis A Evans, Kumar B Rajan

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引用次数: 0

Abstract

Introduction: It is unclear whether inflammation, that is, high interleukin-6 (IL-6) levels, and genetic risk, that is, apolipoprotein E (APOE) ε4 allele, have a compounding effect on cognitive decline (CD).

Methods: We analyzed a subset of participants from the longitudinal cohort study, Chicago Health and Aging Project, comprising 1120 biracial community-dwelling older adults (60% Black and 62% women), and mean follow-up = 6.4 years. We ran adjusted mixed-effects models on2 longitudinal CD.

Results: In APOE ε4 carriers, higher serum IL-6 was not associated with the rate of CD (β = -0.0091 [standard deviation (SD) = 0.0165, p = 0.5800]). Conversely, in non-ε4 carriers, compared to the lower tertile, those with the upper tertile of serum IL-6 levels experienced significantly accelerated CD (β = -0.0257 [SD = 0.0084, p = 0.0023]).

Discussion: Even without the largest genetic risk factor for late-onset Alzheimer's disease/Alzheimer's disease and related dementias (AD/ADRD), elevated serum IL-6 still accelerate the rate of CD in non-APOE ε4 carriers. Hence, interventions ameliorating inflammation may prevent AD/ADRD.

Highlights: Interleukin-6 (IL-6) and the apolipoprotein E (APOE) ε4 allele have been separately associated with an increased risk for cognitive decline, but their interaction remains unclear.In ε4 carriers, IL-6 was not associated with cognitive decline. However, even without the biggest genetic risk factor for Alzheimer's disease (AD), that is, APOE ε4, elevated serum IL-6 still could confer accelerated rate of cognitive decline, with a detrimental effect half of that imposed by APOE ε4 alone.We found no racial differences in these associations.These findings contribute complementary evidence on non-APOE ε4-dependent and non-AD biological pathways through which cognitive decline can still be accelerated in non-APOE ε4 carriers and highlight a specific subgroup of older adults who are at a higher risk of AD and thus may benefit from anti-inflammatory interventions.

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白细胞介素-6 和 APOE 等位基因与双种族社区老年人认知能力下降的前瞻性关联：芝加哥健康与老龄化项目（CHAP）。

导言：目前尚不清楚炎症（即白细胞介素-6（IL-6）水平过高）和遗传风险（即载脂蛋白E（APOE）ε4等位基因）是否会对认知能力下降（CD）产生复合影响：我们分析了纵向队列研究 "芝加哥健康与老龄化项目"（Chicago Health and Aging Project）的参与者子集，其中包括 1120 名居住在社区的双种族老年人（60% 为黑人，62% 为女性），平均随访时间为 6.4 年。我们在 2 个纵向 CD 上运行了调整后的混合效应模型：在 APOE ε4 携带者中，较高的血清 IL-6 与 CD 发生率无关（β = -0.0091 [标准差 (SD) = 0.0165, p = 0.5800]）。相反，在非ε4携带者中，与较低三分位数相比，血清IL-6水平较高三分位数者的CD发生率明显加快（β = -0.0257 [SD = 0.0084, p = 0.0023]）：讨论：即使没有晚期阿尔茨海默病/阿尔茨海默病及相关痴呆症（AD/ADRD）的最大遗传风险因素，血清IL-6升高仍会加速非APOE ε4携带者的CD发病率。因此，改善炎症的干预措施可预防 AD/ADRD：白细胞介素-6（IL-6）和载脂蛋白 E（APOE）ε4 等位基因分别与认知能力下降风险增加有关，但它们之间的相互作用仍不清楚。然而，即使没有阿尔茨海默病（AD）最大的遗传风险因素，即APOE ε4，血清IL-6升高仍会导致认知能力下降速度加快，其不利影响仅为APOE ε4的一半。这些发现为非 APOE ε4 依赖性和非 AD 生物通路提供了补充证据，非 APOE ε4 携带者仍可通过这些通路加速认知功能的衰退，并突出了一个特定的老年人亚群，他们罹患 AD 的风险较高，因此可能受益于抗炎干预措施。

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.