Network Aging Research, Heidelberg University, Heidelberg, Germany.
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
JAMA Netw Open. 2023 Jan 3;6(1):e2252387. doi: 10.1001/jamanetworkopen.2022.52387.
Previous research has suggested an association of kidney function with risk of Alzheimer disease (AD) or other dementias and dementia-related blood biomarkers, but a distinct association remains unclear.
To evaluate the association of kidney function with risk of diagnosis of incident AD or dementia within 17 years and with the blood biomarkers neurofilament light (NfL), phosphorylated tau181 (p-tau181), and glial fibrillary acidic protein (GFAP).
DESIGN, SETTING, AND PARTICIPANTS: In this prospective, population-based cohort study and nested case-control study, 9940 participants in Germany were enrolled between 2000 and 2002 by their general practitioners and followed up for up to 17 years. Participants were included if information on dementia status and creatinine/cystatin C measurements were available. A subsample of participants additionally had measurements of NfL, p-tau181, and GFAP obtained from blood samples. Statistical analysis was performed from January 3 to November 25, 2022.
Impaired kidney function, based on estimated glomerular filtration rate less than 60 mL/min/1.73 m2 according to the 2021 Chronic Kidney Disease Epidemiology Collaboration creatinine-cystatin C equation.
All-cause dementia, AD, and vascular dementia diagnosis, as well as log-transformed levels of NfL, p-tau181, and GFAP in blood.
Of 6256 participants (3402 women [54.4%]; mean [SD] age at baseline, 61.7 [6.6] years), 510 received an all-cause dementia diagnosis within 17 years of baseline. The dementia-related blood biomarker nested case-control sample included 766 participants. After adjusting for age and sex, impaired kidney function at baseline was not associated with a higher risk of all-cause dementia (hazard ratio [HR], 0.95; 95% CI, 0.69-1.29), AD (HR, 0.94; 95% CI, 0.55-1.63), or vascular dementia diagnosis (HR, 1.06; 95% CI, 0.65-1.70) within 17 years. In the cross-sectional analysis, after adjusting for age and sex, impaired kidney function was significantly associated with NfL and p-tau181 levels in blood (NfL: β = 0.47 and P < .001; p-tau181: β = 0.21 and P = .003). After adjusting for age and sex, significant associations with GFAP levels were evident only among men (men: β = 0.31 and P = .006; women: β = -0.12 and P = .11).
In this population-based study of community-dwelling adults, reduced kidney function was associated with increased levels of dementia-related blood biomarkers but not increased dementia risk. Kidney function might influence the accuracy of dementia-related blood biomarkers and should be considered in clinical translation.
先前的研究表明，肾功能与阿尔茨海默病（AD）或其他痴呆症以及与痴呆相关的血液生物标志物的风险之间存在关联，但明确的关联仍不清楚。
评估肾功能与 17 年内发生 AD 或痴呆的风险之间的关联，以及与神经丝轻链（NfL）、磷酸化 tau181（p-tau181）和胶质纤维酸性蛋白（GFAP）等血液生物标志物的关联。
设计、地点和参与者：在这项前瞻性、基于人群的队列研究和嵌套病例对照研究中，德国的 9940 名参与者由他们的全科医生招募，在 2000 年至 2002 年期间入组，并随访长达 17 年。如果有关于痴呆状态和肌酐/胱抑素 C 测量的信息，则纳入参与者。参与者的一个亚组还从血液样本中测量了 NfL、p-tau181 和 GFAP。统计分析于 2022 年 1 月 3 日至 11 月 25 日进行。
根据 2021 年慢性肾脏病流行病学合作组肌酐-胱抑素 C 方程，估计肾小球滤过率低于 60 mL/min/1.73 m2 提示存在肾功能受损。
全因痴呆、AD 和血管性痴呆的诊断，以及血液中 NfL、p-tau181 和 GFAP 的对数值。
在 6256 名参与者（3402 名女性[54.4%]；基线时的平均[标准差]年龄为 61.7[6.6]岁）中，510 名在基线后 17 年内被诊断为全因痴呆。包含痴呆相关血液生物标志物的嵌套病例对照样本包括 766 名参与者。在调整年龄和性别后，基线时肾功能受损与全因痴呆（风险比[HR]，0.95；95%CI，0.69-1.29）、AD（HR，0.94；95%CI，0.55-1.63）或血管性痴呆诊断（HR，1.06；95%CI，0.65-1.70）的风险增加无关。在横断面分析中，在调整年龄和性别后，肾功能受损与血液中的 NfL 和 p-tau181 水平显著相关（NfL：β=0.47，P<0.001；p-tau181：β=0.21，P=0.003）。在调整年龄和性别后，仅在男性中观察到与 GFAP 水平的显著关联（男性：β=0.31，P=0.006；女性：β=-0.12，P=0.11）。
在这项针对社区居住成年人的基于人群的研究中，肾功能下降与痴呆相关的血液生物标志物水平升高有关，但与痴呆风险增加无关。肾功能可能会影响与痴呆相关的血液生物标志物的准确性，在临床转化中应予以考虑。
Zotero 插件