# Elevated vascular endothelial growth factor a is associated with disruption of default network connectivity in older adults

## TL;DR

Higher levels of VEGF-A in older adults are linked to reduced brain network connectivity, which may signal early signs of cognitive decline.

## Contribution

This is the first study to link plasma VEGF-A levels with disruption of the default mode network in older adults.

## Key findings

- VEGF-A levels were negatively associated with default mode network connectivity.
- Higher VEGF-A levels correlated with reduced global efficiency of the network.
- Elevated VEGF-A may indicate early neurocognitive disorder progression.

## Abstract

Vascular Endothelial Growth Factor A (VEGF-A) is an angiogenic signaling protein involved in the maintenance of the cerebral vasculature. No prior study has explored whether plasma VEGF-A levels may be associated with brain functional connectivity changes, such as disruption of the default mode network (DMN), which often precedes the development of cognitive changes in aging. Seventy-six independently living older adults (mean age = 70.3 years; SD = 7.5; 31.6% male) free of dementia or clinical stroke underwent venipuncture and brain MRI. Plasma was assayed for VEGF-A. Using resting state functional MRI, region of interest (ROI) to ROI connectivity and graph theory analysis were conducted to determine average connectivity and global efficiency between each of the following ROIs comprising the DMN: medial prefrontal cortex, lateral parietal cortex and precuneus cortex. Multiple linear regression analysis revealed a significant negative association between VEGF-A levels and DMN connectivity (B = − 0.14, 95% CI (-0.26, − 0.01), p =.038), accounting for age, sex, education, and vascular risk factors. Graph theory analysis similarly revealed that VEGF-A levels are associated with global efficiency of the entire network (B = − 0.18, p =.004). 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 preserving cognitive function warrants further investigation. Clinical Trial Number: N/A; None.

The online version contains supplementary material available at 10.1007/s11682-025-00969-z.