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

IF 4.1 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

ACS Chemical Neuroscience 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

Abstract

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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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

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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来源期刊

ACS Chemical Neuroscience BIOCHEMISTRY & MOLECULAR BIOLOGY-CHEMISTRY, MEDICINAL

CiteScore

9.20

自引率

4.00%

发文量

323

审稿时长

1 months

期刊介绍： ACS Chemical Neuroscience publishes high-quality research articles and reviews that showcase chemical, quantitative biological, biophysical and bioengineering approaches to the understanding of the nervous system and to the development of new treatments for neurological disorders. Research in the journal focuses on aspects of chemical neurobiology and bio-neurochemistry such as the following: Neurotransmitters and receptors Neuropharmaceuticals and therapeutics Neural development—Plasticity, and degeneration Chemical, physical, and computational methods in neuroscience Neuronal diseases—basis, detection, and treatment Mechanism of aging, learning, memory and behavior Pain and sensory processing Neurotoxins Neuroscience-inspired bioengineering Development of methods in chemical neurobiology Neuroimaging agents and technologies Animal models for central nervous system diseases Behavioral research