Kidney Function, Alzheimer Disease Blood Biomarkers, and Dementia Risk in Community-Dwelling Older Adults

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.

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.

At baseline, 2,279 dementia-free participants with available blood samples were included (median age 72 (interquartile range, 61-81) years; 62% female). Lower eGFR was associated with higher median z-score levels of all examined AD blood biomarkers, except Aβ42/40, following a nonlinear relationship. At eGFR = 30 mL/min/1.73 m², estimated differences 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]. During a mean follow-up period of 8.3 (SD, 4.3) years, 362 participants developed dementia. In multivariable-adjusted models, impaired kidney function (eGFR < 60 mL/min/1.73 m²) was not associated with an increased hazard of dementia compared with preserved kidney function (eGFR ≥ 60 mL/min/1.73 m²) (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).

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.