# Association of intraindividual differences in estimated glomerular filtration rates based on cystatin C and creatinine with dementia: A cohort study of the UK Biobank

## TL;DR

This study found that a negative difference in kidney function estimates is linked to higher dementia risk and worse brain health.

## Contribution

The study introduces eGFRdiff as a novel potential biomarker for dementia risk and cognitive decline.

## Key findings

- A negative eGFRdiff was associated with increased dementia risk and worse neuroimaging outcomes.
- Lower eGFRdiff correlated with reduced brain volume and higher white matter hyperintensities.
- eGFRdiff showed associations with poorer cognitive performance across multiple domains.

## Abstract

Dementia is a leading cause of cognitive decline, with Alzheimer’s disease (AD) and vascular dementia (VaD) being the most common subtypes. The intraindividual difference between the estimated glomerular filtration rate based on cystatin C and creatinine (eGFRdiff) may serve as an indicator of the overall health status of an individual. However, the relationships between the eGFRdiff and dementia risk, dementia subtypes, dementia-related neuroimaging changes, and cognitive functions remain unclear.

This study analysed data from over 450,000 participants in the UK Biobank who were followed for up to 15 years. The estimated glomerular filtration rate based on cystatin C (eGFRcys) and creatinine (eGFRcr) was calculated using the CKD-EPI equation, and eGFRdiff was defined as the difference between these values (eGFRdiff = eGFRcys − eGFRcr). Multivariate Cox regression models were used to evaluate the associations between the eGFRdiff and all-cause dementia (ACD), AD, and VaD, whereas cross-sectional analysis were used to examine the relationship among the eGFRdiff, dementia-related neuroimaging changes, and cognitive functions.

Over a median follow-up of 13.5 years, 8,710 participants developed dementia, including 3,910 with AD and 1,893 with VaD. Each one standard deviation increase in eGFRdiff was associated with a reduced risk of dementia, with hazard ratios (95% confidence intervals) of 0.92 (0.90–0.94) for ACD, 0.94 (0.91–0.98) for AD, and 0.90 (0.85–0.94) for VaD. A negative eGFRdiff was associated with adverse neuroimaging changes, including lower total brain and gray matter volumes and higher white matter hyperintensities. Additionally, a negative eGFRdiff was associated with poorer performance across multiple cognitive domains.

A negative eGFRdiff was associated with an increased risk of dementia, adverse neuroimaging outcomes, and cognitive decline. These findings suggest that the eGFRdiff might be considered a potential associative indicator for dementia and cognitive impairment, suggesting potential clinical value in risk assessment and early intervention strategies.