Association of Plasma β-Amyloid with Cognitive Performance and Decline in Chronic Kidney Disease

Abstract

Decreased β-amyloid (Aβ) clearance from the brain has been suggested to contribute to cerebral Aβ accumulation in Alzheimer's disease. Based on the idea of a dynamic Aβ equilibrium in different body compartments, plasma Aβ levels have been investigated as biomarker candidates for preclinical Alzheimer's pathology, yet with inconsistent results. Since the kidneys are involved in Aβ elimination from the blood, we evaluated how chronic kidney disease (CKD) affects the association between plasma Aβ and cognitive deficits and cognitive decline. In 28 CKD patients, stages 3-5D, and 26 control subjects with comparable vascular risk profile from the New Tools for the Prevention of Cardiovascular Disease in Chronic Kidney Disease (NTCVD) cohort, plasma total Aβ was determined with a highly sensitive electrochemiluminescence immunoassay. Cognition was evaluated using a comprehensive battery of ten neuropsychological tests at baseline and 2-year follow-up. Subjects with high plasma Aβ level (above median) demonstrated a significantly worse baseline cognitive performance than subjects exhibiting low Aβ level (summary score of global cognitive performance at baseline z=-0.46±0.76 vs z=-0.08±0.57, p=0.045). Cognitive performance moderately decreased over the 2-year follow-up in subjects with high plasma Aβ level (Δz=-0.13±0.51), but increased in subjects with low plasma Aβ level (Δz=0.16±0.41, p=0.023). In linear regression analyses, baseline plasma Aβ was significantly associated with cognitive decline both in unadjusted analyses (β=-0.28, 95% CI=-0.55 to -0.01) and analyses adjusted for age (β=-0.27, 95% CI=-0.54 to -0.01). Our results suggest the utility of plasma Aβ level in predicting cognitive decline in patients suffering from CKD.