Cognitive Function and Kidney Disease: Baseline Data From the Systolic Blood Pressure Intervention Trial (SPRINT)

Abstract

Background: Chronic kidney disease is common and is associated with cardiovascular disease, cerebrovascular disease, and cognitive function, although the nature of this relationship remains uncertain.

Study design: Cross-sectional cohort using baseline data from the Systolic Blood Pressure Intervention Trial (SPRINT).

Setting & participants: Participants in SPRINT, a randomized clinical trial of blood pressure targets in older community-dwelling adults with cardiovascular disease, chronic kidney disease, or high cardiovascular disease risk and without diabetes or known stroke, who underwent detailed neurocognitive testing in the cognition substudy, SPRINT-Memory and Cognition in Decreased Hypertension (SPRINT-MIND).

Predictors: Urine albumin-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR).

Outcomes: Cognitive function, a priori defined as 5 cognitive domains based on 11 cognitive tests using z scores, and abnormal white matter volume quantified by brain magnetic resonance imaging.

Results: Of 9,361 SPRINT participants, 2,800 participated in SPRINT-MIND and 2,707 had complete data; 637 had brain imaging. Mean age was 68 years, 37% were women, 30% were black, and 20% had known cardiovascular disease. Mean eGFR was 70.8±20.9mL/min/1.73m² and median urine ACR was 9.7 (IQR, 5.7-22.5) mg/g. In adjusted analyses, higher ACR was associated with worse global cognitive function, executive function, memory, and attention, such that each doubling of urine ACR had the same association with cognitive performance as being 7, 10, 6, and 14 months older, respectively. Lower eGFR was independently associated with worse global cognitive function and memory. In adjusted models, higher ACR, but not eGFR, was associated with larger abnormal white matter volume.

Limitations: Cross-sectional only, no patients with diabetes were included.

Conclusions: In older adults, higher urine ACR and lower eGFR have independent associations with global cognitive performance with different affected domains. Albuminuria concurrently identifies a higher burden of abnormal brain white matter disease, suggesting that vascular disease may mediate these relationships.

Keywords: Kidney disease; albuminuria; brain; brain imaging; cardiovascular disease (CVD); cerebrovascular disease; cognition; dementia; estimated glomerular filtration rate (eGFR); executive function; global cognitive function; kidney function; memory; neurocognitive test battery; urinary albumin-creatinine ratio (UACR); white matter volume.

Figure 1

Association of (a) urine albumin-creatinine ratio and (b) estimated glomerular filtration rate (GFR) with cognitive domains, showing non-linear associations between either urine ACR or estimated GFR equations and cognitive performance, shown on the y-axis as the parameter estimate for the ACR or GFR subgroup for each domain. Reference is ACR below 10 mg/g and eGFR of 75 to less than 90 ml/min/1.73m², respectively. In multivariable analyses adjusting for model 3 variables including estimated GFR for ACR models and ACR for estimated GFR models, p for trend for the association with global cognitive function is 0.03 and 0.02, for executive function 0.002 and <0.001, for memory 0.18 and 0.08, for attention/concentration 0.04 and 0.3, and for language 0.9 and 0.3, for ACR and GFR models, respectively. Lines are presented for only global cognitive function.

Figure 1

Association of (a) urine albumin-creatinine ratio and (b) estimated glomerular filtration rate (GFR) with cognitive domains, showing non-linear associations between either urine ACR or estimated GFR equations and cognitive performance, shown on the y-axis as the parameter estimate for the ACR or GFR subgroup for each domain. Reference is ACR below 10 mg/g and eGFR of 75 to less than 90 ml/min/1.73m², respectively. In multivariable analyses adjusting for model 3 variables including estimated GFR for ACR models and ACR for estimated GFR models, p for trend for the association with global cognitive function is 0.03 and 0.02, for executive function 0.002 and <0.001, for memory 0.18 and 0.08, for attention/concentration 0.04 and 0.3, and for language 0.9 and 0.3, for ACR and GFR models, respectively. Lines are presented for only global cognitive function.