Chronic kidney disease and cognitive decline: choroid plexus remodeling, glymphatic dysfunction, and Alzheimer biomarker interpretation

Abstract

Cognitive impairment is common in chronic kidney disease (CKD), yet vascular, uremic, dialysis-related, and neurodegenerative mechanisms are often considered separately. We propose an integrated kidney–brain tissue-environment framework to support neurological interpretation of cognitive, imaging, and biomarker findings in CKD. We conducted a narrative synthesis of clinical, neuroimaging, experimental, and biomarker studies retrieved from PubMed/MEDLINE, Embase, Scopus, and Web of Science through June 2026, focusing on barrier dysfunction, choroid plexus remodeling, cerebrospinal fluid dynamics, neurovascular coupling, white-matter injury, glymphatic-related imaging markers, and Alzheimer disease-related plasma biomarkers. CKD is associated with convergent vascular, inflammatory, toxic, barrier, and neurofluid-related abnormalities that may contribute to a mixed cognitive phenotype. Human studies report choroid plexus enlargement, lower diffusion tensor image analysis along the perivascular space (DTI-ALPS) indices, altered cerebrospinal fluid-related signal coupling, and neurovascular decoupling; however, evidence is predominantly cross-sectional and does not establish temporal or causal sequencing. Choroid plexus enlargement is morphologically nonspecific, while DTI-ALPS reflects a composite tissue environment rather than direct glymphatic flow. Reduced kidney function may also increase plasma phosphorylated tau, amyloid-β, neurofilament light chain, and glial fibrillary acidic protein concentrations. Ratio-based measures may attenuate, but do not uniformly eliminate, kidney-related confounding. CKD should be regarded as an active modifier of cognitive phenotype, neuroimaging interpretation, and plasma biomarker assessment. The proposed framework is testable rather than causal and supports reporting kidney function, dialysis context, and multimodal markers when evaluating cognitive decline.