Associations of the LIBRA index with cognitive resilience to genetic susceptibility to dementia.

IF 5 2区医学 Q1 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH

American journal of epidemiology Pub Date : 2025-05-20 DOI:10.1093/aje/kwaf108

Maude Wagner, Jeanne Neuffer, Quentin Le Grand, Aniket Mishra, Claudine Berr, Stéphanie Debette, Catherine Helmer, Cécile Proust-Lima, Cécilia Samieri

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Abstract

The role of lifestyle and health-related factors in dementia risk has been established. However, how a combination of modifiable risk factors, as reflected by the LIBRA (LIfestyle for BRAin health) index, contributes to cognitive resilience to genetic susceptibility to dementia (CRgen) remains unclear. We selected 6,774 Three-City study participants without dementia at baseline (mean age=74 years) and with ≥2 cognitive measures over time. Genetic risk was defined through ApoE-ε4 carriage alone (ε4-carriers) or combined with high AD-specific genetic risk scores beyond ApoE (ε4-carriers/GRS-high). To define CRgen, we modeled and compared the cognitive slopes of at-risk individuals to their demographically similar peers without genetic risk; at-risk individuals with the most preserved cognition were defined as resilient (ε4-carriers [n=237]; ε4-carrier/GRS-high [n=319]), and the least preserved as non-resilient (ε4-carriers [n=866]; ε4-carrier/GRS-high [n=1,249]). Lower LIBRA risk scores at baseline, denoting healthier lifestyle and reduced dementia risk, were linearly associated with greater odds of CRgen, both in ε4-carriers (odds ratio [OR]=1.11;95%CI=1.05-1.18) and ε4-carriers/GRS-high (OR=1.16;95%CI=1.11-1.22). When examining the LIBRA components, cognitive activity and coronary heart diseases history showed the strongest independent associations with CRgen (all P≤.01). Genetically susceptible older adults can develop cognitive resilience, which may be promoted by lifestyle modifications and health management simultaneously.

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天秤座指数与认知恢复力对痴呆遗传易感性的关系

生活方式和健康相关因素在痴呆风险中的作用已经确定。然而，正如LIBRA（大脑健康生活方式）指数所反映的那样，可改变的风险因素的组合如何有助于认知恢复对痴呆症遗传易感性（CRgen）的影响仍不清楚。我们选择了6774名三市研究参与者，他们在基线时没有痴呆（平均年龄=74岁），并且随着时间的推移有≥2项认知测量。遗传风险通过单独携带ApoE-ε4 （ε4-carrier）或结合ApoE （ε4-carrier /GRS-high）以外的ad特异性高遗传风险评分来定义。为了定义CRgen，我们建模并比较了有风险个体与人口统计学上相似但没有遗传风险的同龄人的认知斜率；认知保存最完好的高危个体被定义为弹性个体(ε4-carrier [n=237]；ε4-载流子/ grs高[n=319])，最小保留为非弹性(ε4-载流子[n=866]；ε4-carrier / GRS-high [n = 1249])。基线时较低的LIBRA风险评分，意味着更健康的生活方式和更低的痴呆风险，与较高的CRgen几率呈线性相关，无论是ε4携带者（比值比[OR]=1.11;95%CI=1.05-1.18）还是ε4携带者/ grs高（OR=1.16;95%CI=1.11-1.22）。在检测LIBRA成分时，认知活动和冠心病病史与CRgen的独立相关性最强（均P≤0.01）。遗传易感的老年人可以发展认知弹性，这可能通过改变生活方式和同时进行健康管理来促进。

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

American journal of epidemiology 医学-公共卫生、环境卫生与职业卫生

CiteScore

7.40

自引率

4.00%

发文量

221

审稿时长

3-6 weeks

期刊介绍： The American Journal of Epidemiology is the oldest and one of the premier epidemiologic journals devoted to the publication of empirical research findings, opinion pieces, and methodological developments in the field of epidemiologic research. It is a peer-reviewed journal aimed at both fellow epidemiologists and those who use epidemiologic data, including public health workers and clinicians.