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

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, peGFRcr-cys<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 m(2), 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 m(2) 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.

Automated summary

This study found impaired kidney function to be a critical risk factor for dementia, with the use of cystatin C strengthening the relationship between CKD and dementia. It highlights the significant value of preserving kidney function to reduce the risk of dementia and suggests considering cystatin C measurement as part of clinical practice in evaluating dementia risk.