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Serum Brain–Derived Neurotrophic Factor and Vascular Endothelial Growth Factor Levels Are Associated With Risk of Stroke and Vascular Brain Injury: Framingham Study
Open accessAbstract
Background and Purpose—: Brain-derived neurotrophic factor (BDNF), a major neurotrophin and vascular endothelial growth factor (VEGF) have a documented role in neurogenesis, angiogenesis, and neuronal survival. In animal experiments, they impact infarct size and functional motor recovery after an ischemic brain lesion. We sought to examine the association of serum BDNF and VEGF with the risk of clinical stroke or subclinical vascular brain injury in a community-based sample. Methods—: In 3440 Framingham Study participants (mean age, 65±11 years; 56% women) who were free of stroke/transient ischemic attack (TIA), we related baseline BDNF and logVEGF to risk of incident stroke/TIA. In a subsample with brain MRI and with neuropsychological tests available (n=1863 and 2104, respectively; mean age, 61±9 years, 55% women, in each), we related baseline BDNF and logVEGF to log-white matter hyperintensity volume on brain MRI, and to visuospatial memory and executive function tests. Results—: During a median follow-up of 10 years, 193 participants experienced incident stroke/TIA. In multivariable analyses adjusted for age, sex, and traditional stroke risk factors, lower BDNF and higher logVEGF levels were associated with an increased risk of incident stroke/TIA (hazard ratio comparing BDNF Q1 versus Q2–Q4, 1.47; 95% confidence interval, 1.09–2.00; P =0.012 and hazard ratio/SD increase in logVEGF, 1.21; 95% confidence interval, 1.04–1.40; P =0.012). Persons with higher BDNF levels had less log-white matter hyperintensity volume (β±SE=−0.05±0.02; P =0.025), and better visual memory (β±SE=0.18±0.07; P =0.005). Conclusions—: Lower serum BDNF and higher VEGF concentrations were associated with increased risk of incident stroke/TIA. Higher levels of BDNF were also associated with less white matter hyperintensity and better visual memory. Our findings suggest that circulating BDNF and VEGF levels modify risk of clinical and subclinical vascular brain injury.
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“Because factors such as age, sex, education, physical activity, and smoking status may determine social relationships and also influence BDNF levels, dementia risk, and stroke risk, we parsimoniously adjusted for a priori variables [4], [25], [26].”
From Associations between social relationship measures, serum brain-derived neurotrophic factor, and risk of stroke and dementia (2017) · cites this paper as [4]
In the citing paper
“Because lower circulating BDNF levels and small social networks have separately been associated with higher risk of incident stroke [3], [4], cognitive dysfunction [2], [5], [6], and the accumulation of Alzheimer's disease pathology [7], [8]”
From Associations between social relationship measures, serum brain-derived neurotrophic factor, and risk of stroke and dementia (2017) · cites this paper as [4]
In the citing paper
“Because lower circulating BDNF levels and small social networks have separately been associated with higher risk of incident stroke [3], [4], cognitive dysfunction [2], [5], [6], and the accumulation of Alzheimer's disease pathology [7], [8]”
From Associations between social relationship measures, serum brain-derived neurotrophic factor, and risk of stroke and dementia (2017) · cites this paper as [4]
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Cites
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MethodSelf-citationAN INVESTIGATION OF CORONARY HEART DISEASE IN FAMILIES
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- 10.1001/archinte.1979.03630450011006 · DOI
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Koenig, H. G., VanderWeele, T. J., & Peteet, J. R. (2023) · doi:10.1093/oso/9780190088859.001.0001 · Cited by 1,160
Neuroinflammatory mechanisms of blood-brain barrier damage in ischemic stroke
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Inflammation and cerebral small vessel disease: A systematic review
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Vascular endothelial growth factor: a neurovascular target in neurological diseases
Lange, C. M., Storkebaum, E., de Almodóvar, C. R., Dewerchin, M. A., & Carmeliet, P. (2016) · Nature Reviews Neurology · doi:10.1038/nrneurol.2016.88 · Cited by 384
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Poggesi, A., Pasi, M., Pescini, F., Pantoni, L., & Inzitari, D. (2015) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2015.116 · Cited by 257
Metadata
- Authors
- Pikula, A., Beiser, A. S., Chen, T. C., Preis, S. R., Vorgias, D., DeCarli, C., Au, R., Kelly-Hayes, M., Kase, C. S., Wolf, P. A., Vasan, R. S., & Seshadri, S.
- Affiliations
- Boston University (US)
- From the Boston University Schools of Medicine and Public Health, Boston, MA (A.P., A.S.B., T.C.C., S.R.P., D.V., R.A., M.K.-H., C.S.K., P.A.W., R.S.V., S.S.); Framingham Heart Study, Framingham, MA (A.P., A.S.B., S.R.P., C.D., R.A., M.K.-H., C.S.K., P.A.W., R.S.V., S.S.); and University of California at Davis, Sacramento (C.D.).
- ORCID
- Venue
- Stroke
- Published
- 2013-10
- Volume
- 44
- Issue
- 10
- Pages
- 2768-2775
- ISSN
- 0039-2499 (ISSN-L)
- 1524-4628
- PMC
- PMC3873715
- OpenAlex
- W2111149177
- Cited by
- 200
- References
- 47
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 15 · 2023: 51 · 2022: 16 · 2021: 10 · 2020: 18 · 2019: 15 · 2018: 12 · 2017: 15 · 2016: 13 · 2015: 17 · 2014: 6
- FWCI
- 8.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Stroke (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- American Heart Association
- National Institutes of Health (UL1TR000157, n01hc25195-41-0-1, n01hv28178-12-0-0)
- National Institute on Aging (R01AG031287, AG031287, AG08122, AG033193, R01AG016495, R01AG033193, R01AG008122)
- National Heart, Lung, and Blood Institute (N01‐HC25195, K24HL004334, N01-HC-025195, N01-HV-028178, R01HL093029, U01HL096917)
- National Institute of Neurological Disorders and Stroke (R01NS017950)
- National Center for Research Resources
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Clinical Neurology › Acute Ischemic Stroke Management
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- brain-derived neurotrophic factor, vascular endothelial growth factor, stroke risk, transient ischemic attack, white matter hyperintensities, vascular brain injury, visuospatial memory, executive function, serum biomarkers, Framingham Heart Study, angiogenesis, neurogenesis, ischemic brain injury, cognitive function, vascular risk factors, sex differences, neuroinflammation
- MeSH terms
- Age Factors, Aged, Brain Ischemia, Female, Follow-Up Studies, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Radiography, Risk Factors, Sex Factors, Incidence, Brain-Derived Neurotrophic Factor, Stroke, Vascular Endothelial Growth Factor A
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