Cognitive Function Scores in Patients with CKD Vary by Sex, Disease Severity

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Using the National Institutes of Health Toolbox Cognition Battery, results showed greater cognitive dysfunction across certain domains based on sex and CKD stage.

Findings from a recent study are calling attention to notable deficits in fluid cognition, dexterity, and total cognition among individuals with chronic kidney disease (CKD), further detailing differences in cognitive function scores based on sex and CKD stage.1

The study, published in Kidney360, leveraged data from participants in the Bicarbonate Administration in CKD trial and found those with more advanced CKD had lower cognitive scores than patients with earlier-stage CKD. Results also showed greater manual dexterity, processing speed and fluidity, language comprehension, and episodic memory scores among female participants, whereas males scored higher for attention and inhibitory control.1

According to the US Centers for Disease Control and Prevention, kidney diseases are a leading cause of death in the United States, with about 37 million US adults estimated to have CKD. Complications linked to CKD can affect virtually every part of the body, although its impact on cognitive and cardiovascular function is especially noteworthy.2,3

“Subgroups among people with CKD could be at greater risk of cognitive dysfunction, although few studies have investigated risk stratification by sex or other cofactors,” Jessica Kendrick, MD, professor of medicine at the University of Colorado Anschutz Medical Campus, and colleagues wrote.1

To assess cognition function and potential sex differences in cognition in adults with CKD, investigators examined National Institutes of Health Toolbox Cognition Battery-measured cognitive function in participants in the Bicarbonate Administration in CKD trial. The trial enrolled adult patients with CKD stage 3b-4, defined as estimated glomerular filtration rate (eGFR) 15-44 mL/min/1.73m2. For inclusion, patients were additionally required to have serum bicarbonate 22-27 mEq/L, blood pressure <140/90 mmHg, and be taking stable anti-hypertensive, anti-hyperglycemic, and lipid-lowering medications for ≥ 1 month.1

The present study included 105 trial participants who were predominantly male (50.5%), non-Hispanic White (77.4%), and had a mean age of 61.6 (Standard deviation [SD], 11.7) years. Participants had advanced kidney disease with a mean eGFR of 35 (SD, 10) mL/min/1.73m2, and 93% had a history of hypertension.1

Investigators measured cognitive function using the National Institutes of Health Toolbox Cognition Battery, which assesses cognitive, sensory, emotional, and motor function, testing both fluid and crystallized cognition. Cognitive testing was performed at the baseline trial visit prior to treatment intervention.1

Investigators reported patients’ total cognition composite scores based on the average of the fluid and crystallized composite scores. They additionally adjusted fully corrected scores for age, sex, education level, and race and ethnicity.1

Compared to the National Institutes of Health Toolbox reference population, participants in the present study scored, on average, below the 50th percentile across all cognitive domain tests and the dexterity test. Investigators pointed out total cognition scores were also below the 50th percentile. Participants scored in the lowest percentiles on the Flanker test, which examines attention and inhibitory control, and on the pegboard test, which measures dexterity.1

Upon analysis, participants with stage 4 CKD had significantly lower fluid cognition scores compared to those with CKD stage 3b (β-estimate, -5.4; 95% CI, -9.8 to -0.9; P = .03). Participants with CKD stage 4 also had significantly lower scores for working memory (β-estimate, -6.2; 95% CI, -10.3 to -2.0; P = .005), but no significant differences were observed for crystallized cognition, total cognition, or dexterity scores based on CKD severity.1

When investigators examined cognition by sex, they noted females scored in a significantly lower percentile than males on the Flanker test but performed significantly better on the episodic memory tests and dexterity tests and had greater crystallized cognition scores compared to males. However, there were no significant differences in fluid or total cognition scores between male and female patients.1

Investigators outlined several potential limitations to the study. These included the small cohort population, fewer patients with CKD stage 4 than stage 3b, lack of data on participants’ duration of CKD or their family history of cognitive dysfunction, and missing information on patients’ anemia status.1

Accordingly, investigators concluded, “Future studies are needed to elucidate the mechanisms by which cognitive dysfunction occurs in CKD and to identify novel therapies to improve cognitive function in CKD.”


  1. Zhang A, Furgeson S, Shapiro A, et al. Assessing Cognition in Chronic Kidney Disease Using the NIH Toolbox®. Kidney360. doi:10.34067/KID.0000000000000440
  2. US Centers for Disease Control and Prevention. Chronic Kidney Disease Basics. Chronic Kidney Disease Initiative. February 28, 2022. Accessed April 12, 2024.
  3. Mayo Clinic. Chronic Kidney Disease. Symptoms and Causes. September 6, 2023. Accessed April 12, 2024.