Impact of kidney function on biomarkers of neurodegeneration, white matter hyperintensities, and cognition in older adults

Abstract

BACKGROUND: We evaluated the association between kidney function, neurodegenerative biomarkers (i.e., neurofilament light chain [NfL], total tau [t-tau], and glial fibrillary acidic protein [GFAP]), white matter hyperintensities, and global cognition. METHODS: The study consisted of 1207 participants living on the south side of Chicago, Illinois, enrolled in the Chicago Health and Aging Project, a population-based cohort since 1993. Kidney function was assessed using the estimated glomerular filtration rate (eGFRcr), calculated according to the 2021 Chronic Kidney Disease Epidemiology (CKD-EPI) based on age, sex, and serum creatinine levels. RESULTS: In a multivariable-adjusted model, lower levels of eGFRcr were associated with higher levels of biomarkers of neurodegeneration. Specifically, for a 1-SD decrease of eGFRcr, there was a 22% increase in NfL levels in serum. eGFRcr levels were not associated with white matter hyperintensities or global cognition. DISCUSSION: Kidney function may be considered when interpreting NfL, GFAP, and t-tau levels for risk stratification in research and clinical applications. Highlights: Kidney function is associated with higher neurfilament light chain (NfL), total tau (t-tau), and glial fibrillary acidic protein (GFAP) serum concentrations, while there was no association with white matter hyperintensities or global cognition. Individuals with severely impaired kidney function had 146.7% higher serum concentrations of NfL when compared to people with normal kidney function. This study suggests assessing kidney function in older adults when interpreting NfL, GFAP, and t-tau levels in the serum for risk stratification.