Horn Jens W, Fohner Alison, Tracy Russell, Adams Hieab H H, Djousse Luc, Romundstad Solfrid, Janszky Imre, Longstreth W T, Mukamal Kenneth J
Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.
Department of Internal Medicine, Levanger Hospital, Health Trust Nord-Trøndelag, Levanger, Norway.
Sci Rep. 2025 Jul 1;15(1):22172. doi: 10.1038/s41598-025-06448-1.
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.
蛋白尿反映全身内皮功能障碍，但其与亚临床脑异常的关系尚未得到全面梳理。心血管健康研究从1989 - 1990年开始，在美国四个社区招募老年人。1996 - 1997年对蛋白尿进行了系统测量；1992 - 1994年和1997 - 1999年进行了两次脑部磁共振成像（MRI）；并对1996 - 1997年储存样本进行血清神经丝轻链（NfL）测量。我们研究了蛋白尿与白质高信号（WMH）和脑室大小的纵向进展、新发梗死以及横断面定量脑容量和神经元损伤循环生物标志物之间的关联（n = 834 - 1950）。即使在调整血管危险因素后，蛋白尿仍与脑室分级恶化（每增加一倍的比值比为1.10，95%置信区间（CI）1.01 - 1.19）和循环NfL水平（每增加一倍升高2%，95% CI 1 - 4%）呈正相关。蛋白尿还与WMH恶化、新发梗死以及定量WMH和海马体积有关，但这些关联似乎反映了心血管危险因素的负担。蛋白尿与脑室大小恶化和循环NfL独立相关，提示微血管功能障碍在脑萎缩中具有特定作用。它还反映了心血管危险因素对血管性脑损伤标志物的负担。这些结果突出了蛋白尿与常见衰老脑异常之间的多种关联。
