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

https://doi.org/10.1053/j.ajkd.2017.04.021Get rights and content

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 ± 20.9 mL/min/1.73 m2 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.

Section snippets

Study Population

A multicenter randomized trial, SPRINT (ClinicalTrials.gov study number NCT01206062) compared 2 strategies for treating systolic blood pressure: one targeted the standard goal of <140 mm Hg, and the other, a more intensive target of <120 mm Hg. Enrollment focused on volunteers 50 years or older with an average baseline systolic blood pressure ≥ 130 mm Hg and evidence of cardiovascular disease, CKD, 10-year Framingham cardiovascular disease risk score ≥ 15%, or age 75 years or older. Major exclusion

Participant Characteristics

Among 2,921 SPRINT participants receiving the extended cognitive battery, 214 were missing key data, including urine ACR (n=152), eGFR (n=22), or sufficient cognitive testing (n=64), with 26 of these individuals missing more than 1 of these items, resulting in 2,707 participants with complete essential data. Participants with missing data were similar to those with complete data except for slightly lower educational achievement. Mean baseline eGFR was 70.8 ± 20.9 mL/min/1.73 m2, and median baseline

Discussion

Among SPRINT-MIND participants, higher urine albumin concentration was independently associated with worse cognitive functioning in multiple domains, including global cognitive function, executive function, and attention, whereas lower eGFR was independently associated with worse global function and memory. The magnitude of association between urine ACR and cognitive performance was notable, with each doubling of urine ACR akin to the effect of being 6 to 14 months older for most cognitive

Acknowledgements

Support: SPRINT is funded with federal funds from the National Institutes of Health (NIH), including the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke, under contract numbers HHSN268200900040C, HHSN268200900046C, HHSN268200900047C, HHSN268200900048C, HHSN268200900049C, and Inter-Agency Agreement Number A-HL-13-002-001. It was

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  • Cited by (0)

    In line with AJKD’s procedures for potential conflicts of interest for editors, described in the Information for Authors & Journal policies, an Editorial Board Member (Morgan E. Grams, MD, PhD, MHS) served as Acting Editor-in-Chief and handled the peer-review and decision-making processes.

    A list of the members of the SPRINT Study Research Group is available at https://www.sprinttrial.org/public/SPRINT_Publications_Acknowledgement_Long_List.pdf

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