Kidney Function Tied to Dementia-Related Biomarkers, Not Dementia Risk

Reduced kidney function was associated with higher NfL and p-tau levels in the blood, but not with AD or all-cause dementia.

Kidney function correlated significantly with blood biomarkers related to dementia and related disorders, but not with increased risk for dementia itself, according to study findings published in JAMA Network Open.

In previous studies, a relationship between kidney function and risk for dementia or Alzheimer disease (AD) has been suggested; however, the exact association between the 2 neurologic disorders is unknown.

To determine the association between kidney function and incident dementia or AD, researchers in Germany conducted a population-based, prospective, cohort study, obtaining data on 9940 participants from another study (ESTHER). They enrolled 6256 of these 9940 individuals (54.4% women; mean age at baseline, 61.7 years) who had available information regarding dementia and baseline kidney assessments between 2000 and 2002 and followed them for up to 17 years. A total of 510 participants received an all-cause dementia diagnosis within 17 years from baseline.

Baseline kidney assessments included serum creatinine and cystatin C levels. The researchers calculated estimate glomerular filtration rate based on an equation using serum creatinine and cystatin C measurements. They used the 2021 Chronic Kidney Disease Epidemiology Collaboration’s definition, which stated that estimated glomerular filtration rates of less than 60 mL/min/1.73 m2 indicated impaired kidney function.

Kidney function might influence the accuracy of dementia-related blood biomarkers and should be considered in clinical translation.

A small subgroup of 766 study participants underwent testing for AD-specific blood biomarkers, including neurofilament light (NfL), phosphorylated tau181 (p-tau181), and glial fibrillary acidic protein (GFAP).

After adjusting for age and sex, the researchers discovered that impaired kidney function did not increase risk for all-cause dementia (hazard ratio [HR], 0.95; 95% CI, 0.69-1.29), vascular dementia (HR, 1.06; 95% CI, 0.65-1.70), or AD (HR, 0.94; 95% CI, 0.55-1.63) during the 17-year study period.

In contrast to this finding, impaired kidney function positively correlated with increased levels of serum NfL (P <.001) and p-tau181 (P =.003) biomarkers. Only men demonstrated a significant association between impaired kidney function and elevated serum GFAP levels (P =.006) compared with women (P =.11).

“In this population-based study of community-dwelling adults, reduced kidney function was associated with increased levels of dementia-related blood biomarkers but not increased dementia risk,” the researchers noted. “Kidney function might influence the accuracy of dementia-related blood biomarkers and should be considered in clinical translation,” they added.

Study limitations included potential misdiagnosis, underdiagnosis, or delayed diagnosis of dementia, a restricted number of dementia-related biomarker measurements, lack of generalizability of results to people outside of European descent, and the very small number of participants in the study with estimated glomerular filtration rates below 30 mL/min/1.73m2 indicative of kidney failure.

This article originally appeared on Neurology Advisor


Stocker H, Beyer L, Trares K, et al. Association of kidney function with development of Alzheimer disease and other dementias and dementia-related blood biomarkers. Published online January 24, 2023. JAMA Netw Open. doi:10.1001/jamanetworkopen.2022.52387