Advanced CKD Linked to Higher Risk of Cognitive Impairment: JAMA

A new study published in the Journal of American Medical Association showed that the severity of chronic kidney disease (CKD) is a significant risk factor for cognitive decline at all stages of the illness, as seen by the increased prevalence of cognitive impairment linked to more advanced stages of CKD.

Cognitive decline is associated with CKD, which raises the risk of dementia. As the illness progresses, impairment gets worse. Proteinuria appears to be more significantly correlated with cognitive impairment, potentially suggesting cerebral small-vessel disease. Yet, few prospective studies included both eGFR and proteinuria. More investigation is required on the severity of CKD. Thus, this study examined relationships between incident cognitive impairment and the severity of CKD as determined by the urine protein to creatinine ratio (UPCR) and estimated glomerular filtration rate (eGFR).

5,607 individuals with chronic renal disease from the CRIC research (enrolled 2003–2008 and 2013–2015; analyses 2024–2025) were examined in this cohort research. UPCR and eGFR were the exposures. Standardized tests were used to evaluate cognitive outcomes, including executive function, memory, attention/processing speed, and global cognition. Impairment was defined as being at least one standard deviation below the baseline mean. Following the removal of baseline impairment, Cox regression assessed the relationships between incident cognitive impairment and eGFR and UPCR while controlling for clinical, lifestyle, and demographic variables.

Depending on the cognitive test, the median follow-up for 5,607 CRIC participants (56.3% males; mean age 59.6 ± 10.8 years) was 4–6 years. Elevated proteinuria (UPCR) raised the likelihood of executive function impairment by 16% and attention/processing speed impairment by 21%.

Additionally, a lower eGFR increased the chance of attention/processing speed impairment by 21%. While eGFR impacts diminished following UPCR modification, UPCR associations remained substantial. Individuals with UPCR ≥150 mg/g and eGFR <60 mL/min/1.73 m² were 38% more likely to experience global cognitive impairment than those with minimal proteinuria and intact renal function.

Overall, a higher frequency of cognitive impairment was prospectively linked to a more advanced stage of CKD. When modeled jointly, the UPCR proved to be a more reliable determinant, despite the fact that both the eGFR and the UPCR showed significant results in their independent studies. 

Reference:

Huang, Z., Yaffe, K., Li, C., Xiao, C., Pan, Y., Sun, X., Anderson, A. H., He, J., Jaar, B. G., Han, H., Kiryluk, K., Rahman, M., Rao, P., Ricardo, A. C., Shah, V. O., Srivastava, A., Taliercio, J. J., Kurella Tamura, M., Unruh, M. L., … Unruh, M. L. (2026). Chronic kidney disease severity and risk of cognitive impairment. JAMA Network Open, 9(2), e2559834. https://doi.org/10.1001/jamanetworkopen.2025.59834