Functional connectome phenotype of multiple cerebrovascular disease markers and its interaction with plasma p-tau181 on downstream outcomes

Motivation: Cerebrovascular disease (CeVD) is assessed by several MRI markers, but their impact on brain functional connectivity (FC) remains unclear. Goal(s): To examine how multiple CeVD markers influence FC, and how CeVD-related FC changes interact with Alzheimer’s disease pathology to influence downstream outcomes. Approach: We studied multivariate associations between four CeVD markers and whole-brain FC in 529 participants, and how this CeVD-related FC phenotype interacted with plasma p-tau181 to influence longitudinal brain atrophy and cognitive decline. Results: We identified a FC phenotype linked to high CeVD burden across all markers. This phenotype and p-tau181 contributed additively, but not synergistically, to atrophy and cognitive decline. Impact: Using a multivariate approach, our study demonstrated that CeVD exerted widespread, non-MRI marker-specific effects on the whole-brain functional connectome. Further, we showed that AD and CeVD have additive but not synergistic effects on neurodegeneration and cognitive changes over time.