Qu Yi, Qin Qi-Xiong, Wang Dan-Lei, Li Jiang-Ting, Zhao Jing-Wei, An Ke, Li Jing-Yi, Mao Zhi-Juan, Min Zhe, Xiong Yong-Jie, Xue Zheng
Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Aging Neurosci. 2023 May 22;15:1130833. doi: 10.3389/fnagi.2023.1130833. eCollection 2023.
The relationship between kidney function and cognitive impairment in Parkinson's disease (PD) is poorly understood and underexplored. This study aims to explore whether renal indices can serve as indicators to monitor the cognitive impairment of PD.
A total of 508 PD patients and 168 healthy controls from the Parkinson's Progression Markers Initiative (PPMI) were recruited, and 486 (95.7%) PD patients underwent longitudinal measurements. The renal indicators including serum creatinine (Scr), uric acid (UA), and urea nitrogen, as well as UA/Scr ratio and estimated glomerular filtration rate (eGFR), were measured. Cross-sectional and longitudinal associations between kidney function and cognitive impairment were evaluated using multivariable-adjusted models.
eGFR was associated with lower levels of cerebrospinal fluid (CSF) A ( = 0.0156) and α-synuclein ( = 0.0151) and higher serum NfL ( = 0.0215) in PD patients at baseline. Longitudinal results showed that decreased eGFR predicted a higher risk of cognitive impairment (HR = 0.7382, 95% CI = 0.6329-0.8610). Additionally, eGFR decline was significantly associated with higher rates of increase in CSF T-tau ( = 0.0096), P-tau ( = 0.0250), and serum NfL ( = 0.0189), as well as global cognition and various cognitive domains ( < 0.0500). The reduced UA/Scr ratio was also linked to higher NfL levels ( = 0.0282) and greater accumulation of T-tau ( = 0.0282) and P-tau ( = 0.0317). However, no significant associations were found between other renal indices and cognition.
eGFR is altered in PD subjects with cognitive impairment, and predict larger progression of cognitive decline. It may assist identifying patients with PD at risk of rapid cognitive decline and have the potential to monitoring responses to therapy in future clinical practice.
帕金森病（PD）患者肾功能与认知障碍之间的关系尚不清楚且研究不足。本研究旨在探讨肾脏指标是否可作为监测PD患者认知障碍的指标。
从帕金森病进展标志物计划（PPMI）中招募了508例PD患者和168名健康对照，486例（95.7%）PD患者接受了纵向测量。测量了包括血清肌酐（Scr）、尿酸（UA）、尿素氮以及UA/Scr比值和估计肾小球滤过率（eGFR）在内的肾脏指标。使用多变量调整模型评估肾功能与认知障碍之间的横断面和纵向关联。
在基线时，PD患者的eGFR与较低水平的脑脊液（CSF）A（β = 0.0156）和α-突触核蛋白（β = 0.0151）以及较高的血清NfL（β = 0.0215）相关。纵向结果显示，eGFR降低预示着认知障碍风险更高（HR = 0.7382，95%CI = 0.6329 - 0.8610）。此外，eGFR下降与CSF T-tau（β = 0.0096）、P-tau（β = 0.0250）和血清NfL（β = 0.0189）的升高率显著相关，以及与整体认知和各个认知领域（P < 0.0500）相关。UA/Scr比值降低也与较高的NfL水平（β = 0.0282）以及T-tau（β = 0.0282）和P-tau（β = 0.0317）的更多积累有关。然而，未发现其他肾脏指标与认知之间存在显著关联。
认知障碍的PD患者中eGFR发生改变，并预测认知衰退的更大进展。它可能有助于识别有快速认知衰退风险的PD患者，并有可能在未来临床实践中监测治疗反应。
