Markers of kidney function, genetic variation related to cognitive function, and cognitive performance in the UK Biobank

Abstract

Background: Chronic kidney disease has been linked to worse cognition. However, this association may be dependent on the marker of kidney function used, and studies assessing modification by genetics are lacking. This study examined associations between multiple measures of kidney function and assessed effect modification by a polygenic score for general cognitive function. Methods: In this cross-sectional study of up to 341,208 European ancestry participants from the UK Biobank study, we examined associations between albuminuria and estimated glomerular filtration rate based on creatinine (eGFRcre) or cystatin C (eGFRcys) with cognitive performance on tests of verbal-numeric reasoning, reaction time and visual memory. Adjustment for confounding factors was performed using multivariate regression and propensity-score matching. Interaction between kidney function markers and a polygenic risk score for general cognitive function was also assessed. Results: Albuminuria was associated with worse performance on tasks of verbal-numeric reasoning (β(points) = -0.09, p < 0.001), reaction time (β(milliseconds) = 7.06, p < 0.001) and visual memory (β(log errors) = 0.013, p = 0.01). A polygenic score for cognitive function modified the association between albuminuria and verbal-numeric reasoning with significantly lower scores in those with albuminuria and a lower polygenic score (p = 0.009). Compared to participants with eGFRcre ≥ 60 ml/min, those with eGFRcre < 60 ml/min had lower verbal-numeric reasoning scores and slower mean reaction times (verbal numeric reasoning β = -0.11, p < 0.001 and reaction time β = 6.08, p < 0.001 for eGFRcre < 60 vs eGFRcre ≥ 60). Associations were stronger using cystatin C-based eGFR than creatinine-based eGFR (verbal numeric reasoning β = -0.21, p < 0.001 and reaction time β = 11.21, p < 0.001 for eGFRcys < 60 vs eGFRcys ≥ 60). Conclusions: Increased urine albumin is associated with worse cognition, but this may depend on genetic risk. Cystatin C-based eGFR may better predict cognitive performance than creatinine-based estimates.