Abstract 70: Rich-Club Behaviour and Analyses in the Human Brain Connectome as Novel Early Biomarkers of Cognitive Decline

Abstract

Introduction: Transient ischemic attack (TIA) patients have an increased risk of early dementia, but the mechanism is unclear. One potential mechanism is the damaging effects of microvascular disease on brain networks. Rich club is a phenomenon where highly connected nodes form a “rich club” amongst themselves, thus playing an important role in global brain network communication. In this study we aim to determine 1) whether the prominence of the rich club effect declines greater in TIA patients than controls over time, and 2) the relationship of rich club prominence with cognition. Methods: TIA patients (n=47) and controls (n=43) underwent DTI imaging and cognitive assessment at baseline, 1-year, 3-year, and 5-year. Whole-brain tractography utilizing constrained spherical deconvolution was performed to construct whole-brain connectomes for both groups at all available timepoints. The maximum normalized rich club coefficient (Φ max ) was used as an indicator of the prominence of the rich club effect. Independent-sample T-tests were used to compare Φ max cross-sectionally, while a linear mixed effect (LME) model was used to examine the longitudinal change in Φ max in TIA patients vs. controls, while controlling for covariates including age, sex, WMH volume, whole-brain volume, and peak width of skeletonized mean diffusivity. Results: TIA patients had a mean age of 63.94 ( SD =8.62) and 20 females. Controls had a mean age of 60.73 (8.16) and 29 females. The prominence of the rich club was not significantly different between TIA patients and controls at baseline or 1-year ( p >0.05). However, TIA patients showed a significantly less prominent rich club at 3-year and 5-year compared to controls ( p =0.047 and 0.018, respectively). TIA patients exhibited a significantly greater decrease in rich club prominence over time, relative to controls ( p =0.023), after accounting for covariates. Longitudinal LME models showed no association between changes in rich club prominence and changes in cognition ( p >0.05 for all cognitive domains). Conclusion: In this study, we show a decrease in rich club prominence in TIA patients compared to controls which might identify their increased risk of cognitive impairment, and the potential benefits of aggressive vascular risk reduction.