Impaired Kidney Function Raises Alzheimer’s Biomarkers Without Increasing Dementia Risk: Study

A new study published in the journal of Neurology showed that reduced kidney function does not raise the incidence of dementia although it is associated with elaborate blood levels of Alzheimer's biomarkers (AD), particularly neurofilament light chain.

Although changes in blood biomarkers of Alzheimer disease have been associated with impaired kidney function, little is known about the underlying processes and how they may contribute to the development of dementia. Therefore, this study investigated the relationships between dementia development, blood-based biomarkers of AD, and estimated glomerular filtration rate (eGFR).

The Swedish National Study on Aging and Care in Kungsholmen, a long-term population-based research project, provided the data. Using eGFR based on serum creatinine, kidney function was evaluated. The Simoa platform was used to evaluate AD biomarkers from peripheral blood samples, including amyloid beta [Aβ42/40], phosphorylated tau [p-tau181 and p-tau217] and total tau [t-tau] proteins, neurofilament light chain [NfL], and glial fibrillary acidic protein [GFAP]. The DSM-IV criteria were used to diagnose dementia. The cross-sectional relationships between eGFR and AD biomarkers were evaluated using quantile regression models, whereas the relationship between kidney function and biomarkers and incident dementia was investigated using Cox regression models.

2,279 individuals without dementia who had blood samples accessible at baseline were included; their median age was 72 (interquartile range: 61–81) years, and 62% of them were female. With the exception of Aβ42/40, all studied AD blood biomarkers showed a nonlinear association between lower eGFR and higher median z-score levels.

The calculated differences for eGFR = 30 mL/min/1.73 m2 were as follows: p-tau181: β, 0.22 [95% CI 0.09–0.35]; p-tau217: β, 0.20 [95% CI 0.10–0.31]; t-tau: β, 0.24 [95% CI 0.05–0.42]; NfL: β, 0.88 [95% CI 0.80–0.95]; GFAP: β, 0.10 [95% CI 0.03–0.16]. 362 patients experienced dementia throughout a mean follow-up period of 8.3 (SD, 4.3) years.

When compared to maintained kidney function (eGFR > 60 mL/min/1.73 m2), impaired kidney function (eGFR < 60 mL/min/1.73 m2) was not linked to a higher risk of dementia in multivariable-adjusted models (hazard ratio [HR], 0.93 [95% CI 0.72–1.21]). People with impaired (as opposed to intact) renal function had a greater correlation between elevated (high vs. low) NfL and dementia (HR, 3.85 [95% CI 1.87–7.95] vs. HR, 1.84 [95% CI 1.34–2.53], respectively).

Overall, elevated levels of the majority of AD blood biomarkers were linked to impaired renal function. However, decreased kidney function appeared to hasten the clinical manifestation of underlying neurodegenerative illness rather than independently raising the risk of dementia.

Source:

Gasparini, F., Valletta, M., Vetrano, D. L., Beridze, G., Rizzuto, D., Calderón-Larrañaga, A., Fredolini, C., Dale, M., Winblad, B., Fratiglioni, L., & Grande, G. (2026). Kidney function, Alzheimer disease blood biomarkers, and dementia risk in community-dwelling older adults. Neurology, 106(1), e214446. https://doi.org/10.1212/WNL.0000000000214446