脑血管疾病功能连接组表型和血浆 p-tau181 对纵向神经变性和认知结果的叠加效应

IF 13 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's & Dementia Pub Date : 2024-11-14 DOI:10.1002/alz.14328

Joanna Su Xian Chong, Fang Ji, Saima Hilal, Joyce Ruifen Chong, Jia Ming Lau, Nathanael Ren Jie Tong, Boon Yeow Tan, Narayanaswamy Venketasubramanian, Mitchell Kim Peng Lai, Christopher Li‐Hsian Chen, Juan Helen Zhou

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引用次数: 0

摘要

引言我们研究了多种脑血管疾病（CeVD）神经影像学标志物对大脑功能连接性（FC）的影响，以及这种与CeVD相关的FC变化如何与血浆磷酸化tau（p-tau）181（一种阿尔茨海默病[AD]标志物）相互作用，从而影响下游神经变性和认知变化.方法使用偏最小二乘法相关性检验了痴呆症谱系中529名参与者的四种CeVD标志物与全脑FC之间的多变量关联。使用线性混合效应模型研究了CeVD相关FC模式和p-tau181对纵向灰质体积（GMV）和认知变化的交互影响。讨论我们的研究结果表明，CeVD 对大脑连接组产生了整体影响，并强调了 AD 和 CeVD 对神经退化和认知的叠加作用。研究发现了一种与高负担CeVD标记物相关的全球网络表型。CeVD表型和血浆磷酸化tau 181对下游结果的影响是叠加的。

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Additive effects of cerebrovascular disease functional connectome phenotype and plasma p‐tau181 on longitudinal neurodegeneration and cognitive outcomes

INTRODUCTIONWe investigated the effects of multiple cerebrovascular disease (CeVD) neuroimaging markers on brain functional connectivity (FC), and how such CeVD‐related FC changes interact with plasma phosphorylated tau (p‐tau)181 (an Alzheimer's disease [AD] marker) to influence downstream neurodegeneration and cognitive changes.METHODSMultivariate associations among four CeVD markers and whole‐brain FC in 529 participants across the dementia spectrum were examined using partial least squares correlation. Interactive effects of CeVD‐related FC patterns and p‐tau181 on longitudinal gray matter volume (GMV) and cognitive changes were investigated using linear mixed‐effects models.RESULTSWe identified a brain FC phenotype associated with high CeVD burden across all markers. Further, expression of this general CeVD‐related FC phenotype and p‐tau181 contributed additively, but not synergistically, to baseline and longitudinal GMV and cognitive changes.DISCUSSIONOur findings suggest that CeVD exerts global effects on the brain connectome and highlight the additive nature of AD and CeVD on neurodegeneration and cognition.Highlights

Effects of multiple cerebrovascular disease (CeVD) markers on functional connectivity were studied.

A global network phenotype linked to high burden across CeVD markers was identified.

CeVD phenotype and plasma phosphorylated tau 181 contributed additively to downstream outcomes.

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来源期刊

Alzheimer's & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

期刊介绍： Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.