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痴呆与肾功能障碍和血浆生物标志物的关联:一项基于人群的研究。

Association of dementia with impaired kidney function and plasma biomarkers: A population-based study.

机构信息

Department of Neurology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People's Republic of China.

Shandong Provincial Clinical Research Center for Neurological Diseases, Jinan, Shandong, People's Republic of China.

出版信息

Eur J Neurol. 2024 Dec;31(12):e16488. doi: 10.1111/ene.16488. Epub 2024 Sep 27.

Abstract

BACKGROUND AND PURPOSE

Emerging evidence has linked impaired kidney function with dementia in older adults, but the neuropathological pathways underlying their association remain poorly understood. We sought to examine the relationships of kidney function with dementia and plasma biomarkers in a Chinese rural population.

METHODS

This population-based study used data from the baseline examination of the Multimodal Interventions to Delay Dementia and Disability in rural China (MIND-China) cohort (March-September 2018; n = 5715). Kidney function was assessed using estimated glomerular filtration rate (eGFR) based on serum creatinine level. Dementia, Alzheimer's disease (AD) and vascular dementia (VaD) were diagnosed according to the international criteria. Plasma biomarkers were measured using the SIMOA platform in a subsample (n = 1446). Data were analyzed using logistic, general linear, and mediation models.

RESULTS

Of the 5715 participants, 306 were diagnosed with dementia, including 195 with AD and 100 with VaD. Impaired kidney function (eGFR <60 vs. ≥90 mL/min/1.73 m) was associated with multivariable-adjusted odds ratios of 2.24 (95% confidence interval [CI] 1.44-3.46) for all-cause dementia, 1.85 (1.07-3.18) for AD, and 2.49 (1.16-5.22) for VaD. In the biomarker subsample, impaired kidney function was significantly associated with higher plasma amyloid-β (Aβ)40 (β-coefficient = 54.36, 95% CI 43.34-65.39), Aβ42 (β-coefficient = 3.14, 95% CI 2.42-3.86), neurofilament light chain (β-coefficient = 10.62, 95% CI 5.62-15.62), and total tau (β-coefficient = 0.68, 95% CI 0.44-0.91), and a lower Aβ42/Aβ40 ratio (β-coefficient = -4.11, 95% CI -8.08 to -0.14). The mediation analysis showed that plasma total tau significantly mediated 21.76% of the association between impaired kidney function and AD (p < 0.05).

CONCLUSION

Impaired kidney function is associated with dementia and plasma biomarkers among rural-dwelling older Chinese adults, and the association with AD is partly mediated by plasma biomarkers for neurodegeneration.

摘要

背景与目的

越来越多的证据表明,老年人的肾功能受损与痴呆有关,但两者之间的关联的神经病理学途径仍知之甚少。我们试图在中国农村人群中研究肾功能与痴呆和血浆生物标志物的关系。

方法

本研究基于中国农村多模态干预延缓痴呆和残疾的基线研究(MIND-China 队列)的数据(2018 年 3 月至 9 月;n=5715)。采用血清肌酐水平估算肾小球滤过率(eGFR)来评估肾功能。根据国际标准诊断痴呆、阿尔茨海默病(AD)和血管性痴呆(VaD)。在亚样本(n=1446)中使用 SIMOA 平台测量血浆生物标志物。使用逻辑回归、一般线性和中介模型进行数据分析。

结果

在 5715 名参与者中,有 306 名被诊断为痴呆,包括 195 名 AD 和 100 名 VaD。与 eGFR<60ml/min/1.73m 相比,eGFR<60ml/min/1.73m 与全因痴呆、AD 和 VaD 的多变量调整比值比分别为 2.24(95%可信区间[CI] 1.44-3.46)、1.85(1.07-3.18)和 2.49(1.16-5.22)相关。在生物标志物亚样本中,肾功能不全与较高的血浆淀粉样蛋白-β40(Aβ40)(β 系数=54.36,95%CI 43.34-65.39)、Aβ42(β 系数=3.14,95%CI 2.42-3.86)、神经丝轻链(β 系数=10.62,95%CI 5.62-15.62)和总 tau(β 系数=0.68,95%CI 0.44-0.91)显著相关,与 Aβ42/Aβ40 比值降低(β 系数=-4.11,95%CI-8.08 至-0.14)显著相关。中介分析表明,血浆总 tau 显著介导了肾功能不全与 AD 之间 21.76%的关联(p<0.05)。

结论

肾功能受损与中国农村老年人的痴呆和血浆生物标志物有关,与 AD 的关联部分由神经退行性变的血浆生物标志物介导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b1d/11555029/561a47307708/ENE-31-e16488-g003.jpg

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