Abstract #4964

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

Joanna Su Xian Chong¹, Fang Ji¹, Saima Hilal^2,3,4, Joyce Ruifen Chong^3,4, Jia Ming Lau¹, Boon Yeow Tan⁵, Narayanaswamy Venketasubramanian^3,6, Mitchell Kim Peng Lai^3,4, Christopher Li-Hsian Chen^3,4, and Juan Helen Zhou^1,7,8

¹Centre for Sleep and Cognition & Centre for Translational Magnetic Resonance Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore, ²Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore, ³Memory Ageing & Cognition Centre, National University Health System, Singapore, Singapore, ⁴Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore, ⁵St Luke’s Hospital, Singapore, Singapore, ⁶Raffles Neuroscience Centre, Raffles Hospital, Singapore, Singapore, ⁷Integrative Sciences and Engineering Programme (ISEP), National University of Singapore, Singapore, Singapore, ⁸Department of Electrical and Computer Engineering, National University of Singapore, Singapore, Singapore

Synopsis

Keywords: Functional Connectivity, Alzheimer's Disease, Cerebrovascular disease

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.

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