一项基于人群的研究中，血管负担和遗传风险与认知能力及痴呆症的关联

Vascular burden and genetic risk in association with cognitive performance and dementia in a population-based study.

作者信息

Georgakis Marios K, Ntanasi Eva, Ramirez Alfredo, Grenier-Boley Benjamin, Lambert Jean-Charles, Sakka Paraskevi, Yannakoulia Mary, Kosmidis Mary H, Dardiotis Efthimios, Hadjigeorgiou Georgios M, Charissis Sokratis, Mourtzi Niki, Hatzimanolis Alexandros, Scarmeas Nikolaos

机构信息

Institute for Stroke and Dementia Research (ISD), University Hospital, Ludwig-Maximilians-University LMU, Feodor-Lynen-Str. 17, Munich 81377, Germany.

Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.

出版信息

Cereb Circ Cogn Behav. 2022 May 5;3:100145. doi: 10.1016/j.cccb.2022.100145. eCollection 2022.

DOI:10.1016/j.cccb.2022.100145

PMID:36324400

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9616333/

Abstract

BACKGROUND AND PURPOSE

Vascular risk factors may influence cognitive function and thus represent possible targets for preventive approaches against dementia. Yet it remains unknown, if they associate with cognition independently of the individual genetic risk for dementia.

METHODS

In a population-based study of 1172 community-dwelling individuals aged ≥65 years in Greece, we constructed a vascular burden score (VBS; based on presence of hypertension, diabetes, hyperlipidemia, heart disease, and cerebrovascular disease, range 0-5) and a polygenic risk score (PRS) for clinically-diagnosed Alzheimer's disease (AD) based on 23 genetic variants. We then explored in joint models the associations of the PRS for AD and VBS with global cognitive performance, cognitive performance across multiple cognitive domains, and odds of dementia.

RESULTS

The mean age of study participants was 73.9 ± 5.2 years (57.1% females). Both the PRS for AD and VBS were associated with worse global cognitive performance (beta per-SD-increment in PRS: -0.06, 95%CI: -0.10 to -0.02, beta per-point-increment in VBS: -0.05, 95%CI: -0.09 to -0.02), worse performance across individual cognitive domains (memory, executive function, attention, language, visuospatial ability), and higher odds of dementia (OR per-SD increment in PRS: 1.56, 95%CI: 1.17-2.09, OR per-point increment in VBS: 1.38, 95%CI: 1.05-1.81). There was no evidence of an interaction between the two scores. Higher VBS was associated with worse cognitive performance equally across tertiles of the PRS for AD, even among individuals at the highest tertile.

CONCLUSIONS

Both genetic risk and vascular burden are independently and additively associated with worse cognitive performance and higher odds of dementia.

摘要

背景与目的

血管危险因素可能影响认知功能，因此是预防痴呆症的潜在靶点。然而，这些因素是否独立于个体患痴呆症的遗传风险而与认知相关仍不清楚。

方法

在希腊一项针对1172名年龄≥65岁的社区居民的基于人群的研究中，我们构建了一个血管负担评分（VBS；基于高血压、糖尿病、高脂血症、心脏病和脑血管疾病的存在情况，范围为0至5）以及一个基于23个基因变异的临床诊断阿尔茨海默病（AD）的多基因风险评分（PRS）。然后，我们在联合模型中探讨了AD的PRS和VBS与整体认知表现、多个认知领域的认知表现以及痴呆症几率之间的关联。

结果

研究参与者的平均年龄为73.9±5.2岁（57.1%为女性）。AD的PRS和VBS均与较差的整体认知表现相关（PRS每标准差增加的β值：-0.06，95%置信区间：-0.10至-0.02；VBS每增加一分的β值：-0.05，95%置信区间：-0.09至-0.02），在各个认知领域（记忆、执行功能、注意力、语言、视觉空间能力）的表现较差，以及患痴呆症的几率较高（PRS每标准差增加的OR值：1.56，95%置信区间：1.17至2.09；VBS每增加一分的OR值：1.38，95%置信区间：1.05至-1.81）。没有证据表明两个评分之间存在相互作用。较高的VBS与AD的PRS三分位数中较差的认知表现同样相关，即使在最高三分位数的个体中也是如此。