Kidney Function, Alzheimer Disease Blood Biomarkers, and Dementia Risk in Community-Dwelling Older Adults
Francesca Gasparini, Martina Valletta, Davide Liborio Vetrano, Giorgi Beridze, Debora Rizzuto, Amaia Calderón‐Larrañaga, Claudia Fredolini, Matilda Dale, Bengt Winblad, Laura Fratiglioni, Giulia Grande
Abstract
BACKGROUND AND OBJECTIVES: Impaired kidney function has been linked to altered concentrations of blood biomarkers of Alzheimer disease (AD), but the underlying mechanisms and its potential role in dementia development remain poorly understood. We explored the associations between estimated glomerular filtration rate (eGFR), blood-based biomarkers of AD, and dementia development. METHODS: Data were extracted from the Swedish National Study on Aging and Care in Kungsholmen, an ongoing longitudinal population-based study. Kidney function was assessed using eGFR based on serum creatinine. AD biomarkers (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]) were measured from peripheral blood samples using the Simoa platform. Dementia was diagnosed according to DSM-IV criteria. Quantile regression models assessed the cross-sectional associations between eGFR and AD biomarkers; Cox regression models were used to examine the association of kidney function and biomarkers with incident dementia. RESULTS: ) (hazard ratio [HR], 0.93 [95% CI 0.72-1.21]). The relationship between increased (high vs low) NfL and dementia was stronger among individuals with impaired (vs preserved) kidney function (HR, 3.85 [95% CI 1.87-7.95] vs HR, 1.84 [95% CI 1.34-2.53], respectively). DISCUSSION.: Impaired kidney function was associated with elevated circulating level of most AD blood biomarkers. However, the presence of impaired kidney function did not independently increase the risk of dementia but rather seemed to accelerate the clinical expression of underlying neurodegenerative pathology.