白蛋白尿和估计肾小球滤过率作为中年和老年痴呆风险因素：来自 ARIC 研究的发现。
Albuminuria and Estimated GFR as Risk Factors for Dementia in Midlife and Older Age: Findings From the ARIC Study.
机构信息
Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD.
The MIND Center, University of Mississippi Medical Center, Jackson, MS.
出版信息
Am J Kidney Dis. 2020 Dec;76(6):775-783. doi: 10.1053/j.ajkd.2020.03.015. Epub 2020 May 16.
RATIONALE & OBJECTIVE: Evidence is limited on how estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (UACR) relate to dementia at different ages. We evaluated eGFR and UACR in midlife and older age as risk factors for dementia. Additionally, we assessed whether the association between eGFR and dementia is altered when cystatin C and β-microglobulin (B2M) levels are used for GFR estimation.
STUDY DESIGN
Prospective cohort study.
SETTING & PARTICIPANTS: Two baselines from the Atherosclerosis Risk in Communities (ARIC) Study were used: visit 4 (1996-1998), including 9,967 participants 54 to 74 years old, and visit 5 (2011-2013), including 4,626 participants 70 to 90 years old. Participants were followed up until 2017.
PREDICTORS
Log(UACR); eGFR based on creatinine, cystatin C, creatinine and cystatin C, or B2M levels (denoted as eGFR, eGFR, eGFR, and eGFR).
OUTCOME
Incident dementia.
ANALYTICAL APPROACH
Multivariable Cox proportional hazards regression models fit separately for each of the 5 predictors and based on a change in the predictor equivalent to the interquartile range for that predictor at visit 4 (IQR). eGFR models were adjusted for log(UACR) and log(UACR) models were adjusted for eGFR.
RESULTS
We observed 1,821 dementia cases after visit 4 and 438 cases after visit 5. Dementia risk increased with higher albuminuria levels (HRs per IQR [equivalent to 4.2-fold greater log albuminuria] of 1.15 [95% CI, 1.09-1.21] after visit 4 and 1.27 [95% CI, 1.13-1.42] after visit 5). An association with lower eGFR was seen for only eGFR (HRs per IQR [equivalent to 24.3mL/min/1.73m lesser eGFR] of 1.12 [95% CI, 1.04-1.21] after visit 4 and 1.30 [95% CI, 1.12-1.52] after visit 5) and eGFR (HRs per IQR [equivalent to 18.3mL/min/1.73m lesser eGFR] of 1.15 [95% CI, 1.07-1.23] after visit 4 and 1.34 [95% CI, 1.17-1.55] after visit 5). Differences between these associations in midlife and older age were not statistically significant.
LIMITATIONS
Changes in potentially time-varying covariates were not measured. Dementia was not subclassified by cause.
CONCLUSIONS
Albuminuria was consistently associated with dementia incidence. Lower eGFR based on cystatin C or B2M, but not creatinine, levels was also associated with dementia. Risk associations were similar when kidney measures were assessed at midlife and older age.
背景与目的
关于估算肾小球滤过率（eGFR）和尿白蛋白-肌酐比值（UACR）在不同年龄与痴呆的相关性，现有证据有限。我们评估了中年和老年时的 eGFR 和 UACR 作为痴呆的风险因素。此外，我们评估了当使用胱抑素 C 和β-微球蛋白（B2M）水平来估计 GFR 时，eGFR 与痴呆之间的关联是否发生改变。
研究设计
前瞻性队列研究。
地点和参与者
使用来自社区动脉粥样硬化风险研究（ARIC）的两次基线数据：第 4 次访视（1996-1998 年），包括 9967 名 54-74 岁的参与者；第 5 次访视（2011-2013 年），包括 4626 名 70-90 岁的参与者。参与者随访至 2017 年。
预测因子
UACR 的自然对数值；基于肌酐、胱抑素 C、肌酐和胱抑素 C 或 B2M 水平的 eGFR（分别表示为 eGFR、eGFR、eGFR 和 eGFR）。
结局
新发痴呆。
分析方法
分别对 5 个预测因子中的每一个进行多变量 Cox 比例风险回归模型拟合，并根据预测因子的变化，将其调整为相当于第 4 次访视时预测因子的四分位距（IQR）（IQR 相当于 log 白蛋白尿增加 4.2 倍）。eGFR 模型根据 log(UACR)进行调整，log(UACR)模型根据 eGFR 进行调整。
结果
第 4 次访视后观察到 1821 例痴呆病例，第 5 次访视后观察到 438 例。白蛋白尿水平升高与痴呆风险增加相关（第 4 次访视后 IQR[相当于 log 白蛋白尿增加 4.2 倍]的 HR 为 1.15[95%CI，1.09-1.21]，第 5 次访视后为 1.27[95%CI，1.13-1.42]）。只有 eGFR 与较低的 eGFR 相关（第 4 次访视后 IQR[相当于 eGFR 减少 24.3mL/min/1.73m]的 HR 为 1.12[95%CI，1.04-1.21]，第 5 次访视后为 1.30[95%CI，1.12-1.52]）和 eGFR（第 4 次访视后 IQR[相当于 eGFR 减少 18.3mL/min/1.73m]的 HR 为 1.15[95%CI，1.07-1.23]，第 5 次访视后为 1.34[95%CI，1.17-1.55]）。中年和老年时这些关联之间的差异在统计学上无显著性。
局限性
潜在的时变协变量的变化未被测量。痴呆未按病因进行分类。
结论
白蛋白尿与痴呆的发病率始终相关。基于胱抑素 C 或 B2M 的 eGFR 降低（而非肌酐）与痴呆也相关。当在中年和老年评估肾脏指标时，风险关联相似。
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