Luo Li, Gansevoort Ron T, Kieneker Lyanne M, Yang Yuanhang, Bosi Alessandro, de Boer Rudolf A, Franssen Casper F M, Eriksdotter Maria, Carrero Juan-Jesus, Xu Hong
Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
J Intern Med. 2025 Nov;298(5):489-503. doi: 10.1111/joim.70022. Epub 2025 Sep 23.
The association between albuminuria and dementia has been insufficiently studied, possibly due to not considering dementia subtypes, the interplay with estimated glomerular filtration rate (eGFR), and the use of varying albuminuria measurement techniques.
This study aimed to investigate the eGFR-independent risk of all-cause and type-specific dementia associated with albuminuria, measured by the urine albumin-creatinine ratio (ACR) and dipstick.
The main analysis included 132,869 subjects aged ≥65 years without a history of dementia and with at least one ACR test from the Stockholm Creatinine Measurements (SCREAM) project between 2006 and 2019. The primary and secondary outcomes were the incidence of all-cause dementia and type-specific dementia, respectively. Cox regression models were used to calculate hazard ratios (HRs, 95% CIs).
During a median follow-up of 3.9 (interquartile ranges, 1.8-7.1) years, 9435 (7%) subjects developed incident dementia. After multivariable adjustments, including eGFR, an ACR level of 30-299 and ≥300 mg/g was associated with a 25% (HR, 1.25; 95% CI, 1.19-1.31) and a 37% (HR, 1.37; 95% CI, 1.23-1.51) higher risk of developing all-cause dementia, respectively, compared to an ACR level of <30 mg/g. Higher ACR levels were also associated with an increased risk of mixed, vascular, and unspecified dementia, but not with Alzheimer's disease. These findings were robust in subjects with at least one dipstick proteinuria test.
Increased albuminuria is associated with a higher risk of all-cause dementia, particularly mixed, vascular, and unspecified dementia, independent of baseline eGFR and generalizable across different clinical pathways of albuminuria testing.
蛋白尿与痴呆之间的关联尚未得到充分研究，这可能是由于未考虑痴呆亚型、与估算肾小球滤过率（eGFR）的相互作用以及使用了不同的蛋白尿测量技术。
本研究旨在调查通过尿白蛋白肌酐比值（ACR）和试纸法测量的、与eGFR无关的蛋白尿与全因性痴呆及特定类型痴呆的风险。
主要分析纳入了132869名年龄≥65岁、无痴呆病史且在2006年至2019年期间至少进行过一次来自斯德哥尔摩肌酐测量（SCREAM）项目的ACR检测的受试者。主要和次要结局分别为全因性痴呆和特定类型痴呆的发病率。采用Cox回归模型计算风险比（HRs，95%可信区间）。
在中位随访3.9年（四分位间距，1.8 - 7.1年）期间，9435名（7%）受试者发生了新发痴呆。在进行包括eGFR在内的多变量调整后，与ACR水平<30 mg/g相比，ACR水平为30 - 299 mg/g和≥300 mg/g时发生全因性痴呆的风险分别高25%（HR，1.25；95%可信区间，1.19 - 1.31）和37%（HR，1.37；95%可信区间，1.23 - 1.51）。较高的ACR水平还与混合性、血管性和未分类痴呆的风险增加相关，但与阿尔茨海默病无关。这些发现在至少进行过一次试纸法蛋白尿检测的受试者中是稳健的。
蛋白尿增加与全因性痴呆风险较高相关，尤其是混合性、血管性和未分类痴呆，独立于基线eGFR，且可推广至不同的蛋白尿检测临床途径。
