tau病理介导血管风险负担与非痴呆老年人认知障碍的关联：CABLE研究

Tau Pathologies Mediate the Associations of Vascular Risk Burden with Cognitive Impairments in Non-demented Elders: The CABLE Study.

作者信息

Yu G-X, Ou Y-N, Bi Y-L, Ma Y-H, Hu H, Wang Z-T, Hou X-H, Xu W, Tan L, Yu J-T

机构信息

Prof. Jin-Tai Yu, Department of Neurology, Huashan Hospital, Fudan University, No. 12 Wulumuqi Road, Shanghai, China; Prof. Lan Tan, Department of Neurology, Qingdao Municipal Hospital, Dalian Medical University, No.5 Donghai Middle Road, Qingdao, China, E-mail addresses:

出版信息

J Prev Alzheimers Dis. 2022;9(1):136-143. doi: 10.14283/jpad.2021.55.

DOI:10.14283/jpad.2021.55

PMID:35098984

Abstract

BACKGROUND

Studies suggested that vascular dysfunction might increase the risk of developing Alzheimer's disease (AD), but the underlying mechanisms still remain obscure.

OBJECTIVE

To evaluate the associations of vascular risk burden with AD core pathologies and investigate the effects of AD core pathologies on relationships between vascular risk burden and cognitive impairments.

DESIGN

The Chinese Alzheimer's Biomarker and LifestyLE (CABLE) study was principally focusing on aging, as well as the risk factors and biomarkers of AD initiated in 2017.

SETTING

The CABLE study was a large cohort study established in Qingdao, China.

PARTICIPANTS

A total of 618 non-demented elders were obtained from CABLE study.

MEASUREMENTS

The general vascular risk burden was assessed by the Framingham General Cardiovascular Risk Score (FGCRS). Multivariate linear regression analyses were performed to evaluate the associations of FGCRS with cerebrospinal fluid (CSF) AD biomarkers and cognition. Casual mediation analyses were performed to investigate the mediating effects of AD biomarkers on cognition.

RESULTS

Increased FGCRS was related to higher levels of CSF total tau (t-tau, p < 0.001), phosphorylated tau (p-tau, p < 0.001) as well as the ratio of t-tau and amyloid-β 42 (t-tau/Aβ42, p = 0.010), and lower Chinese-Modified Mini-Mental State Examination (CM-MMSE, p = 0.010) score. Stratified analysis indicated that age modified the associations, with FGCRS being significantly associated with tau pathology (p < 0.001 for t-tau and p-tau) in middle-aged group (<65 years old), instead of older group. The influences of FGCRS on cognitive impairments were partially mediated by tau pathologies (a maximum proportion of 20.9%).

CONCLUSIONS

Tau pathology might be a pivotal mediator for effects of vascular risk on cognitive decline. Early and comprehensive intervention for vascular risk factors might be a potential approach to delaying or preventing cognitive impairment and AD.

摘要

背景

研究表明，血管功能障碍可能会增加患阿尔茨海默病（AD）的风险，但其潜在机制仍不清楚。

目的

评估血管风险负担与AD核心病理之间的关联，并研究AD核心病理对血管风险负担与认知障碍之间关系的影响。

设计

中国阿尔茨海默病生物标志物与生活方式（CABLE）研究主要聚焦于衰老以及2017年启动的AD风险因素和生物标志物。

地点

CABLE研究是在中国青岛开展的一项大型队列研究。

参与者

从CABLE研究中选取了618名非痴呆老年人。

测量

采用弗雷明汉心血管总体风险评分（FGCRS）评估总体血管风险负担。进行多变量线性回归分析以评估FGCRS与脑脊液（CSF）AD生物标志物及认知之间的关联。进行因果中介分析以研究AD生物标志物对认知的中介作用。

结果

FGCRS升高与CSF总tau蛋白（t-tau，p<0.001）、磷酸化tau蛋白（p-tau，p<0.001）水平升高以及t-tau与淀粉样β蛋白42的比值（t-tau/Aβ42，p=0.010）升高相关，且与中国修订版简易精神状态检查表（CM-MMSE，p=0.010）评分降低相关。分层分析表明年龄会改变这种关联，在中年组（<65岁）中FGCRS与tau病理显著相关（t-tau和p-tau的p<0.001），而在老年组中并非如此。FGCRS对认知障碍的影响部分由tau病理介导（最大比例为20.9%）。