Abstract 11433: Elevated Vascular Endothelial Growth Factor A is Associated with Disruption of Default Network Connectivity

Introduction: Vascular Endothelial Growth Factor A (VEGF-A) is an angiogenic signaling protein involved in the maintenance of the cerebral vasculature. VEGF-A may play a role in the pathogenesis of Alzheimer’s disease and vascular dementia; however, whether elevated VEGF-A levels indicate a pathophysiolocal response or protective mechanism remains unclear. No prior study has explored whether VEGF-A levels may be associated with changes in functional connectivity among brain regions prior to the development of cognitive decline. Hypothesis: Disruption of the default network often precedes the development of cognitive changes. In a sample of older adults, we hypothesized that VEGF-A levels may be associated with default network connectivity, indicating early involvement of VEGF-A in disease processes. Methods: Forty-six independently living older adults (mean age = 72.0 years; SD = 6.4; 34.8% male) free of dementia or clinical stroke underwent venipuncture and brain MRI. Plasma was assayed for VEGF-A. Using resting state functional MRI, blood-oxygen level dependent (BOLD) time series from all voxels in each region of interest (ROI) was averaged to determine mean ROI activity. Medial prefrontal cortex, lateral parietal cortex and precuneus cortex ROIs comprised the default network. Results: Accounting for age and sex, multiple linear regression analysis revealed a significant negative association between VEGF-A levels and default mode network connectivity (B =-.0007, 95% CI (-.0012, -.0002), p = .0096). This association persisted after adjusting for APOE4 carrier status and Framingham score. A significant association was present in both APOE4 carriers (p = .019) and non-carriers (p = .029). Conclusions: Prior studies evaluating the association between VEGF-A levels and cognition have been conflicted. This study is the first to examine whether VEGF-A may be linked to early changes in brain network connectivity which precede cognitive decline. These findings suggest that VEGF-A may be elevated early in the progression of neurocognitive disorders. Whether higher levels of VEGF-A contribute to the pathogenesis of neurocognitive disorders or play a protective role in persevering cognitive function warrants further investigation.