2025 American Academy of Neurology Abstract Website

Objective:

To evaluate whether impaired kidney function is a risk factor for dementia and compare the performance of different measures of calculating estimated glomerular filtration rate (eGFR).

Background:

Increasing evidence suggests a close linkage between impaired renal function and dementia. However, previous studies have conflicting results and limitations such as small sample size and single measurement for eGFR based on creatinine.

Design/Methods:

A total of 275,167 participants from the UK Biobank were included in this study. 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 (VD).

Results:

We observed a U-shaped relationship between each eGFR and risk of all-cause dementia and VD, with eGFRcys and eGFRcr-cys showing a closer linkage (p_eGFRcys< 0.0001, p_eGFRcr-cys < 0.0001 and p_eGFRcr= 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/1.73m², adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause dementia for eGFRcr-cys 30-59, <30, and ≥ 105 ml/min/1.73m² 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.

Conclusions:

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 kidney function 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.