Additive effects of cerebrovascular disease functional connectome phenotype and plasma p‐tau181 on longitudinal neurodegeneration and cognitive outcomes
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INTRODUCTION
We 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.
METHODS
Multivariate 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.
RESULTS
We 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.
DISCUSSION
Our 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
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Effects of multiple cerebrovascular disease (CeVD) markers on functional connectivity were studied.
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A global network phenotype linked to high burden across CeVD markers was identified.
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CeVD phenotype and plasma phosphorylated tau 181 contributed additively to downstream outcomes.
