Elevated vascular endothelial growth factor a is associated with disruption of default network connectivity in older adults - PubMed (original) (raw)

. 2025 Apr;19(2):379-383.

doi: 10.1007/s11682-025-00969-z. Epub 2025 Feb 4.

Jung Yun Jang 2, Allison C Engstrom 1, Trevor Lohman 3, Shubir Dutt 4, John Paul M Alitin 3, Isabel J Sible 5, Anisa Marshall 5, Fatemah Shenasa 1, Aimee Gaubert 3, Amy Nguyen 3, David Robert Bradford 6, Kathleen Rodgers 6, S Duke Han 3 7, Daniel A Nation 8 9

Affiliations

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

Arunima Kapoor et al. Brain Imaging Behav. 2025 Apr.

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.

Keywords: Default network connectivity; Vascular endothelial growth factor A.

© 2025. The Author(s).

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethical approval: Appropriate Institutional Ethics Committee(s) have reviewed and approved the study protocol described in the manuscript. This study was approved by the Institutional Review Board at University of Southern California and University of California, Irvine; all participants gave informed consent. Competing interests: The authors declare no competing interests.

Figures

Fig. 1

Fig. 1

Partial regression plot of association between VEGF-A levels and DMN connectivity. Note: Higher VEGF-A levels are associated with decreased connectivity, adjusting for age, sex, education, and vascular risk factors

Fig. 2

Fig. 2

Global efficiency of default network as a function of VEGF-A levels. Note: The effect of VEGF-A levels on DMN connectivity is attributed to decreased efficiency between these nodes. Nodes are represented as blue circles, with strength of global efficiency represented by the size of the circle. Black lines represent edges between nodes

References

    1. Dvorak, H. F., Brown, L. F., Detmar, M., & Dvorak, A. M. (1995). Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. The American Journal of Pathology, 146(5), 1029–1039. -PMC -PubMed
    1. Hedden, T., Van Dijk, K. R. A., Becker, J. A., Mehta, A., Sperling, R. A., Johnson, K. A., & Buckner, R. L. (2009). Disruption of functional connectivity in clinically normal older adults harboring amyloid Burden. The Journal of Neuroscience, 29(40), 12686–12694. 10.1523/JNEUROSCI.3189-09.2009 -DOI -PMC -PubMed
    1. Hohman, T. J., Bell, S. P., & Jefferson, A. L. (2015). The role of vascular endothelial growth factor in Neurodegeneration and Cognitive decline. JAMA Neurology, 72(5), 520. 10.1001/jamaneurol.2014.4761 -DOI -PMC -PubMed
    1. Holmes, D. I., & Zachary, I. (2005). The vascular endothelial growth factor (VEGF) family: Angiogenic factors in health and disease. Genome Biology, 6(2), 209. 10.1186/gb-2005-6-2-209 -DOI -PMC -PubMed
    1. Jang, J. Y., Han, S. D., Yew, B., Blanken, A. E., Dutt, S., Li, Y., Ho, J. K., Gaubert, A., & Nation, D. A. (2021). Resting-state functional connectivity signatures of apathy in community-living older adults. Frontiers in Aging Neuroscience, 13. 10.3389/fnagi.2021.691710 -PMC -PubMed

MeSH terms

Substances

Grants and funding

LinkOut - more resources