A large-scale study revealed that decreased kidney function could correlate with cognitive decline and specific brain changes, highlighting the complex relationship between kidney and brain health.
The research, published in Alzheimer's & Dementia, analyzed data from 15,897 individuals in the CARTaGENE cohort, including brain imaging data from 1,397 participants over a 6-year period. The study found that lower estimated glomerular filtration rate (eGFR) was associated with reduced cognitive performance across multiple domains, including reasoning, working memory, and reaction time. These associations remained significant after adjusting for various factors such as age, sex, education, and cardiovascular risk factors.
"Lower eGFR correlated with reduced cognitive performance and brain structure. Brain regions associated with eGFR were enriched for mitochondrial and inflammatory-related genes," the study authors reported.
The imaging component of the study revealed that decreased kidney function was linked to cortical thinning in specific brain regions, particularly in the frontoparietal cortex, precuneus, cuneus, and dorsolateral prefrontal cortex. Notably, these changes occurred independently from traditional risk factors such as age, body mass index, and white matter lesion volume.
The research team from the University of Montreal employed advanced imaging transcriptomics to characterize the genetic features of affected brain regions. Their analysis showed that areas of cortical thinning associated with lower eGFR demonstrated increased expression of genes involved in mitochondrial function and inflammatory processes.
A particularly significant finding was that eGFR levels mediated the relationship between reasoning ability and brain structure. This effect was most pronounced in patients with moderately decreased kidney function, suggesting early associations between kidney function and cognitive decline.
The study also revealed an intriguing correlation between the pattern of brain changes associated with decreased kidney function and patterns seen in prodromal synucleinopathies, such as REM sleep behavior disorder, a precursor to Parkinson's disease.
While the study population primarily included individuals with mild or no kidney disease, significant associations were detected even within this narrow range of kidney function. The researchers noted this limitation while emphasizing the strength of findings measurable effects even in early stages of decreased kidney function.
These findings contributed to the growing understanding of what researchers termed the "kidney-brain axis." The study suggested that monitoring kidney function might serve as an early indicator of cognitive decline risk, though further research may be needed to fully understand these mechanisms.
"This study highlights the link between reduced eGFR, cognitive impairment, and brain structure, revealing some of the kidney-brain axis mechanisms," the study authors concluded in their discussion.
The researchers indicated that cognitive function should be monitored in patients with decreased kidney function, even in early stages. They also noted that longitudinal studies with repeated cognitive assessments would be valuable to better understand how cognitive decline progresses in relation to kidney function over time.
The authors declared having no competing interests.