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.

中文翻译：

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脑血管疾病功能连接组表型与血浆 p-tau181 对纵向神经退行性变和认知结局的累加效应


引言我们研究了多种脑血管疾病 （CeVD） 神经影像学标志物对脑功能连接 （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）相互作用以影响下游神经退行性和认知变化。方法使用偏最小二乘相关检查痴呆谱系中 529 名参与者的 4 个 CeVD 标志物与全脑 FC 之间的多元关联。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。结果我们确定了所有标志物中与高 CeVD 负荷相关的脑 FC 表型。此外，这种一般 CeVD 相关 FC 表型和 p-tau181 的表达对基线和纵向 GMV 以及认知变化有加加作用，但不是协同作用。讨论我们的研究结果表明，CeVD 对大脑连接组产生整体影响，并突出了 AD 和 CeVD 对神经退行性和认知的累加性。亮点 研究了多种脑血管病 （CeVD） 标志物对功能连接的影响。确定了与 CeVD 标志物的高负担相关的全球网络表型。CeVD 表型和血浆磷酸化 tau 181 对下游结局有累加作用。