Background: Reduced kidney function has been associated with cognitive decline. Most studies have examined a single marker of kidney function and have limited duration of follow-up.
Objective: This study evaluated associations between markers of kidney function (urine albumin, estimated glomerular filtration rate [eGFR], and hyperuricemia) with cognitive performance over time.
Methods: This is a longitudinal study of 1,634 community-dwelling adults (mean age = 71.7 years), with kidney function markers and cognitive ability measured at baseline (1992-1996) and at up to five additional time points with a maximum of 23.4 years (mean = 8.1 years) of follow-up. Associations between kidney function and cognitive performance were assessed using linear mixed effects models. Testing for interaction by sex was conducted.
Results: Albuminuria (urine albumin-to-creatinine ratio [ACR]≥30 mg/g) was associated with steeper annual declines in global cognitive function (MMSE, β= -0.12, p = 0.003), executive function (Trails B, β= 4.50, p < 0.0001) and episodic memory (Buschke total recall, β= -0.62, p = 0.02) scores in men. Results were similar when cognitive test scores were regressed on latent trajectory classes of ACR. In men, hyperuricemia (serum uric acid [SUA]≥6.8 mg/dl for men and SUA≥6.0 mg/dl for women) was associated with lower baseline MMSE (β= -0.70, p = 0.009) scores but not with MMSE change over time. No such associations were detected in women. There were no significant associations between eGFR and cognitive performance for either sex.
Conclusion: In older men, albuminuria is an independent predictor of subsequent cognitive decline. More investigations are needed to explain the observed sex differences and the potential relationship between hyperuricemia and poorer global cognition.
Keywords: Albuminuria; cognitive aging; dementia; glomerular filtration rate; uric acid.