Albuminuria, structural brain findings and Circulating biomarkers of brain injury in older adults

Abstract Albuminuria reflects systemic endothelial dysfunction, but its relationships with subclinical brain abnormalities have not been comprehensively catalogued. The Cardiovascular Health Study recruited older adults from four US communities, beginning in 1989–1990. Systematic measurements of alb...

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Main Authors: Jens W. Horn, Alison Fohner, Russell Tracy, Hieab H. H. Adams, Luc Djousse, Solfrid Romundstad, Imre Janszky, W. T. Longstreth, Kenneth J. Mukamal
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-06448-1
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author Jens W. Horn
Alison Fohner
Russell Tracy
Hieab H. H. Adams
Luc Djousse
Solfrid Romundstad
Imre Janszky
W. T. Longstreth
Kenneth J. Mukamal
author_facet Jens W. Horn
Alison Fohner
Russell Tracy
Hieab H. H. Adams
Luc Djousse
Solfrid Romundstad
Imre Janszky
W. T. Longstreth
Kenneth J. Mukamal
author_sort Jens W. Horn
collection DOAJ
description Abstract Albuminuria reflects systemic endothelial dysfunction, but its relationships with subclinical brain abnormalities have not been comprehensively catalogued. The Cardiovascular Health Study recruited older adults from four US communities, beginning in 1989–1990. Systematic measurements of albuminuria were performed in 1996–1997; two brain MRIs, in 1992–1994 and 1997–1999; and serum neurofilament light chain (NfL) measurements from 1996–1997 stored samples. We examined the associations of albuminuria with longitudinal progression of white matter hyperintensities (WMH) and ventricular size, incident infarcts, and cross-sectional quantitative brain volumes and circulating biomarkers of neuronal injury (n = 834–1950). Albuminuria was positively associated with ventricular grade worsening (odds ratio per doubling 1.10, 95% confidence interval (CI) 1.01–1.19) and with circulating NfL levels (2% higher per doubling, 95% CI 1–4%), even after adjustment for vascular risk factors. Albuminuria was also associated with worsening of WMH, incident infarcts, and quantitative WMH and hippocampal volumes, but these latter associations appeared to reflect burden of cardiovascular risk factors. Albuminuria is independently associated with worsening ventricular size and circulating NfL, suggesting a specific role of microvascular dysfunction in brain atrophy. It also reflects cardiovascular risk factor burden on markers of vascular brain injury. These results highlight the diverse associations of albuminuria with common brain abnormalities of aging.
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spelling doaj-art-87a15eb760ae4c1fae83ce80c72efe352025-08-20T04:01:35ZengNature PortfolioScientific Reports2045-23222025-07-0115111110.1038/s41598-025-06448-1Albuminuria, structural brain findings and Circulating biomarkers of brain injury in older adultsJens W. Horn0Alison Fohner1Russell Tracy2Hieab H. H. Adams3Luc Djousse4Solfrid Romundstad5Imre Janszky6W. T. Longstreth7Kenneth J. Mukamal8Department of Public Health and Nursing, Norwegian University of Science and TechnologyDepartment of Epidemiology, University of WashingtonDepartment of Pathology & Laboratory Medicine and Biochemistry, Larner College of Medicine, University of VermontDepartment of Clinical Genetics and Department of Radiology and Nuclear Medicine, Erasmus University Medical CenterDivision of Aging, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical SchoolDepartment of Internal Medicine, Levanger Hospital, Health Trust Nord-TrøndelagDepartment of Public Health and Nursing, Norwegian University of Science and TechnologyDepartment of Epidemiology, University of WashingtonDepartment of Medicine, Beth Israel Deaconess Medical CenterAbstract Albuminuria reflects systemic endothelial dysfunction, but its relationships with subclinical brain abnormalities have not been comprehensively catalogued. The Cardiovascular Health Study recruited older adults from four US communities, beginning in 1989–1990. Systematic measurements of albuminuria were performed in 1996–1997; two brain MRIs, in 1992–1994 and 1997–1999; and serum neurofilament light chain (NfL) measurements from 1996–1997 stored samples. We examined the associations of albuminuria with longitudinal progression of white matter hyperintensities (WMH) and ventricular size, incident infarcts, and cross-sectional quantitative brain volumes and circulating biomarkers of neuronal injury (n = 834–1950). Albuminuria was positively associated with ventricular grade worsening (odds ratio per doubling 1.10, 95% confidence interval (CI) 1.01–1.19) and with circulating NfL levels (2% higher per doubling, 95% CI 1–4%), even after adjustment for vascular risk factors. Albuminuria was also associated with worsening of WMH, incident infarcts, and quantitative WMH and hippocampal volumes, but these latter associations appeared to reflect burden of cardiovascular risk factors. Albuminuria is independently associated with worsening ventricular size and circulating NfL, suggesting a specific role of microvascular dysfunction in brain atrophy. It also reflects cardiovascular risk factor burden on markers of vascular brain injury. These results highlight the diverse associations of albuminuria with common brain abnormalities of aging.https://doi.org/10.1038/s41598-025-06448-1EpidemiologyRisk factorsMagnetic resonance imageAlbuminuriaCerebral small vessel diseaseNeurofilament light chain
spellingShingle Jens W. Horn
Alison Fohner
Russell Tracy
Hieab H. H. Adams
Luc Djousse
Solfrid Romundstad
Imre Janszky
W. T. Longstreth
Kenneth J. Mukamal
Albuminuria, structural brain findings and Circulating biomarkers of brain injury in older adults
Scientific Reports
Epidemiology
Risk factors
Magnetic resonance image
Albuminuria
Cerebral small vessel disease
Neurofilament light chain
title Albuminuria, structural brain findings and Circulating biomarkers of brain injury in older adults
title_full Albuminuria, structural brain findings and Circulating biomarkers of brain injury in older adults
title_fullStr Albuminuria, structural brain findings and Circulating biomarkers of brain injury in older adults
title_full_unstemmed Albuminuria, structural brain findings and Circulating biomarkers of brain injury in older adults
title_short Albuminuria, structural brain findings and Circulating biomarkers of brain injury in older adults
title_sort albuminuria structural brain findings and circulating biomarkers of brain injury in older adults
topic Epidemiology
Risk factors
Magnetic resonance image
Albuminuria
Cerebral small vessel disease
Neurofilament light chain
url https://doi.org/10.1038/s41598-025-06448-1
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