Introduction Chronic kidney disease 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 association between eGFR and cognitive function in 15,897 individuals from the CARTaGENE cohort. We performed vertex-based MRI analyses between eGFR and cortical thickness in the 1,397 participants who underwent brain MRI after six 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, body mass index, 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.

The authors have declared no competing interest.

This study did not receive any funding

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IRB of the McGill University Health Centre and the Centre integre universitaire de sante et de services sociaux du Nord de l'Ile de Montreal

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