Association of Kidney Function with Risk of Incident Dementia: A Prospective Cohort Study of 275,167 UK Biobank Participants

Article type: Research Article

Authors: Wu, Xin-Rui^{a; 1} | Wu, Kai-Min^{a; 1} | Deng, Yue-Ting^a | Huang, Shu-Yi^a | Yang, Liu^a | Dong, Qiang^a | Feng, Jian-Feng^{b; c} | Cheng, Wei^{b; c} | Yu, Jin-Tai^{a; *}

Affiliations: [a] Department of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontier Center for Brain Science, Fudan University, Shanghai, China | [b] Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China | [c] Department of Computer Science, University of Warwick, Coventry, UK

Correspondence: [*] Correspondence to: Prof. Jin-Tai Yu, MD, PhD, Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, 12th Wulumuqi Zhong Road, Shanghai 200040, China. Tel.: +86 21 52888160; Fax: +86 21 62483421; E-mail: jintai_yu@fudan.edu.cn.

Note: [1] These authors contributed equally to this work.

Abstract: Background:Previous studies have reported inconsistent associations between chronic kidney disease (CKD) and dementia. Objective:To evaluate whether CKD is a risk factor for dementia and compare the performance of different measures of calculating estimated glomerular filtration rate (eGFR). Methods:275,167 participants from UK Biobank were included and eGFR at baseline was calculated using serum creatinine (eGFRcr), cystatin C (eGFRcys), and creatinine-cystatin C equations (eGFRcr-cys). Restricted cubic splines and Cox regression models were performed to assess the relationship of eGFR with all-cause dementia, Alzheimer’s disease (AD), and vascular dementia (VaD). Results:We observed a U-shaped relationship between each eGFR and risk of all-cause dementia and VaD, with eGFRcys and eGFRcr-cys showing a closer linkage (peGFRcys <0.0001, peGFRcrhboxcys<0.0001 and peGFRcr = 0.0001). Lower and supranormal eGFR were related to increased risk of all-cause dementia. Compared to the reference category of 90–104 ml/min/1.73 m2, adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause dementia for eGFRcr-cys 30–59, <30, and ≥105 ml/min/1.73 m2 were 1.26 (95% CI [1.05–1.50], p = 0.012), 2.62 (95% CI [1.54–4.47], p < 0.001), and 1.41 (95% CI [1.17–1.70], p < 0.001). No statistically significant association was observed between eGFR with risk of AD. Conclusion:This prospective study identified impaired kidney function as a critical risk factor for dementia and noted the application of cystatin C strengthened the relationship between CKD and dementia, underlining the significant value of preserving kidney function to reduce the risk of dementia and considering cystatin C measurement as part of clinical practice.

Keywords: Creatinine, cystatin C, dementia, glomerular filtration rate, kidney function

DOI: 10.3233/JAD-220609

Journal: Journal of Alzheimer's Disease, vol. 90, no. 3, pp. 1249-1261, 2022