Background: Albuminuria and estimated glomerular filtration rate (eGFR) are each associated with increased risk of cognitive impairment, but their joint association is unknown. Study Design: Prospective cohort study. Setting & Participants: A US national sample of 19,399 adults without cognitive impairment at baseline participating in the REGARDS (Reasons for Geographic and Racial Disparities in Stroke) Study. Predictors: Albuminuria was assessed using urine albumin-creatinine ratio (UACR) and GFR was estimated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation. Outcomes: Incident cognitive impairment was defined as score ≤4 on the 6-Item Screener at the last follow-up visit. Results: During a mean follow-up of 3.8 ± 1.5 years, UACRs of 30-299 and <300 mg/g were associated independently with 31% and 57% higher risk of cognitive impairment, respectively, relative to individuals with UACR <10 mg/g. This finding was strongest for those with high eGFRs and attenuated at lower levels (P = 0.04 for trend). Relative to eGFR <60 mL/min/1.73 m 2, eGFR <60 mL/min/1.73 m 2 was not associated independently with cognitive impairment. However, after stratifying by UACR, eGFR <60 mL/min/1.73 m 2 was associated with a 30% higher risk of cognitive impairment in participants with UACR <10 mg/g, but not higher UACRs (P = 0.04 for trend). Limitations: Single measures of albuminuria and eGFR, screening test of cognition. Conclusions: When eGFR was preserved, albuminuria was associated independently with incident cognitive impairment. When albuminuria was <10 mg/g, low eGFR was associated independently with cognitive impairment. Albuminuria and low eGFR are complementary, but not additive, risk factors for incident cognitive impairment.
