Serum Bicarbonate Concentration and Cognitive Function in Hypertensive Adults

Abstract

Background and objectives: Cognitive function worsens as kidney function declines, but mechanisms contributing to this association are not completely understood. Metabolic acidosis, a common complication of CKD, leads to neural networks overexcitation and is involved in cerebral autoregulation. We aimed to evaluate the association between serum bicarbonate concentration as a measure of metabolic acidosis, and cognitive function in hypertensive adults with and without CKD.

Design, setting, participants, & measurements: Five cognitive summary scores were measured (global cognitive function, executive function, memory, attention/concentration, and language) in 2853 participants in the Systolic BP Intervention Trial (SPRINT). Multivariable linear regression models adjusted for demographics, comorbidities, systolic BP, medications, eGFR and albuminuria evaluated the cross-sectional association between bicarbonate and cognition at SPRINT baseline. In a subset (n=681) who underwent brain magnetic resonance imaging, the models were adjusted for white matter hyperintensity volume, vascular reactivity, and cerebral blood flow.

Results: The mean age (SD) was 68 (8.5) years. Global cognitive and executive functions were positively associated with serum bicarbonate (estimate [SEM]: 0.014 [0.006]; P=0.01, and 0.018 [0.006]; P=0.003, respectively). Each 1 mEq/L lower bicarbonate level had a similar association with global cognitive and executive function as being 4.3 and 5.4 months older, respectively. The association with global cognition persisted after magnetic resonance imaging findings adjustment (estimate [SEM]: 0.03 [0.01]; P=0.01). There was no association between serum bicarbonate level and memory, attention/concentration, and language.

Conclusions: In a large cohort of hypertensive adults, higher serum bicarbonate levels were independently associated with better global cognitive and executive performance. (ClinicalTrials.gov: NCT01206062).

Keywords: Adult; Attention; Bicarbonate; Bicarbonates; Cerebrovascular Circulation; Cognition; Cohort Studies; Comorbidity; Cross-Sectional Studies; Demography; Executive Function; Homeostasis; Humans; Language; Linear Models; Magnetic Resonance Imaging; Memory; Renal Insufficiency, Chronic; White Matter; acidosis; albuminuria; blood pressure; chronic kidney disease; cognitive function.

Graphical abstract