Daniel E Weiner1, Sarah A Gaussoin2, John Nord3, Alexander P Auchus4, Gordon J Chelune5, Michel Chonchol6, Laura Coker7, William E Haley8, Anthony A Killeen9, Paul L Kimmel10, Alan J Lerner11, Suzanne Oparil12, Mohammad G Saklayen13, Yelena M Slinin14, Clinton B Wright15, Jeff D Williamson16, Manjula Kurella Tamura17. 1. Tufts Medical Center, Boston, MA. Electronic address: dweiner@tuftsmedicalcenter.org. 2. Department of Biostatistical Sciences, Wake Forest University School of Medicine, Winston-Salem, NC. 3. University of Utah and George E. Wahlen VAMC, Salt Lake City, UT. 4. University of Mississippi Medical Center, Jackson, MS. 5. University of Utah School of Medicine, Salt Lake City, UT. 6. University of Colorado Anschutz Medical Campus, Aurora, CO. 7. Department of Social Sciences and Health Policy, Wake Forest University School of Medicine, Winston-Salem, NC. 8. Mayo Clinic, Jacksonville, FL. 9. University of Minnesota, Minneapolis, MN. 10. National Institutes of Health, National Institute of Diabetes Digestive and Kidney Diseases, Bethesda, MD. 11. Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, OH. 12. University of Alabama at Birmingham, Birmingham, AL. 13. Dayton VA Medical Center, Dayton, OH. 14. Minneapolis Veteran's Administration Healthcare System and University of Minnesota, Minneapolis, MN. 15. Wake Forest University School of Medicine, Winston-Salem, NC. 16. University of Miami, Miami, FL. 17. Palo Alto VA Health Care System and Stanford University, Palo Alto, CA.
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.
RCT Entities:
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.
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