The interaction between circadian syndrome and genetic susceptibility in the risk of incident dementia: A longitudinal cohort study.

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The Journal of Prevention of Alzheimer's Disease Pub Date : 2025-05-01 Epub Date: 2025-02-07 DOI:10.1016/j.tjpad.2025.100089

Linling Yu, Wei Liu, Chenqi Liao, Na Shen, Anding Liu, Liming Cheng, Xiong Wang

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引用次数: 0

Abstract

Background: Despite growing interest in circadian disturbances as potential triggers for dementia, the specific impact of circadian syndrome (CircS) on dementia incidence remains poorly understood. Moreover, the role of genetic susceptibility modulating these effects remains to be explored.

Methods: Dementia-free participants from the UK Biobank cohort were included in the analysis. To evaluate the association between CircS and the incidence of dementia, as well as the modifying influence of genetic susceptibility on this relationship, Cox proportional hazards models were utilized.

Results: During a median follow-up period of 14.55 years, 3,965 incident dementia cases were documented. CircS was found to significantly increased the risk of incident dementia, with a hazard ratio (HR) of 1.401 (95 % confidence interval [CI]: 1.296, 1.516). Compared to a CircS score of ≤3, mild CircS (HR: 1.259, 95 % CI: 1.146-1.383), moderate CircS (HR: 1.667, 95 % CI: 1.461-1.903), and severe CircS (HR: 2.028, 95 % CI: 1.397-2.944) were all significantly associated with an elevated risk of dementia. There were significant multiplicative interactions between CircS and genetic susceptibility (P_interaction<0.001). Participants with both a high polygenic risk score (PRS) and CircS had the highest risk of incident dementia (HR: 2.551, 95 % CI: 2.169, 3.001), compared to those with a low PRS and no CircS.

Conclusions: CircS was associated with an increased risk of dementia, which might be aggravated by genetic susceptibility.

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昼夜节律综合征和遗传易感性在痴呆发生风险中的相互作用：一项纵向队列研究。

背景：尽管人们对昼夜节律紊乱作为痴呆的潜在诱因越来越感兴趣，但昼夜节律综合征（CircS）对痴呆发病率的具体影响仍知之甚少。此外，遗传易感性调节这些效应的作用仍有待探索。方法：来自英国生物银行队列的无痴呆参与者被纳入分析。为了评估CircS与痴呆发病率之间的关系，以及遗传易感性对这种关系的调节作用，我们使用了Cox比例风险模型。结果：在14.55年的中位随访期间，记录了3965例痴呆病例。CircS显著增加痴呆发生的风险，风险比（HR）为1.401（95%可信区间[CI]: 1.296, 1.516）。与CircS评分≤3的患者相比，轻度CircS （HR: 1.259, 95% CI: 1.146-1.383）、中度CircS （HR: 1.667, 95% CI: 1.461-1.903）和重度CircS （HR: 2.028, 95% CI: 1.397-2.944）均与痴呆风险升高显著相关。CircS与遗传易感性之间存在显著的倍增性相互作用(pinteraction结论：CircS与痴呆风险增加相关，而遗传易感性可能会加重痴呆风险。

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

The Journal of Prevention of Alzheimer's Disease Medicine-Psychiatry and Mental Health

CiteScore

9.20

自引率

0.00%

发文量

期刊介绍： The JPAD Journal of Prevention of Alzheimer’Disease will publish reviews, original research articles and short reports to improve our knowledge in the field of Alzheimer prevention including: neurosciences, biomarkers, imaging, epidemiology, public health, physical cognitive exercise, nutrition, risk and protective factors, drug development, trials design, and heath economic outcomes.JPAD will publish also the meeting abstracts from Clinical Trial on Alzheimer Disease (CTAD) and will be distributed both in paper and online version worldwide.We hope that JPAD with your contribution will play a role in the development of Alzheimer prevention.