Lower estimated glomerular filtration rate relates to cognitive impairment and brain alterations.

Introduction: Chronic kidney disease (CKD) is associated with cognitive decline and changes in brain structure. However, their associations remain unclear, particularly the selective vulnerability characteristics that make some brain regions more vulnerable.

Methods: We investigated the baseline association between estimated glomerular filtration rates (eGFR) and cognitive function in 15,897 individuals from the CARTaGENE cohort. We performed vertex-based magnetic resonance imaging (MRI) analyses between eGFR and longitudinal cortical thickness in the 1397 participants who underwent brain MRI after 6 years. Imaging transcriptomics was used to characterize the gene expression and neurodegenerative features associated with this association.

Results: Lower eGFR correlated with reduced cognitive performance and brain structure. Brain regions associated with eGFR were enriched for mitochondrial and inflammatory-related genes. These associations occurred independently from age, sex, education, and body mass index (BMI), Framingham risk score, and white matter lesion volume.

Discussion: This study highlights the link between reduced eGFR, cognitive impairment, and brain structure, revealing some of the kidney-brain axis mechanisms.

Highlights: Lower eGFR is associated with reduced cognitive abilities.Structural brain changes are mediated by eGFR levels.Specific gene expression patterns correlate with lower eGFR and brain changes.Mitochondrial and inflammation-related genes were enriched in these patterns.