Cognitive impairment is increasingly recognized as a common and clinically relevant complication of chronic kidney disease (CKD), but substantial inter-individual heterogeneity exists in both neuroimaging phenotypes and cognitive outcomes, with underlying biological mechanisms poorly understood.
Research questions:
*Can CKD participants be classified into distinct and reproducible neuroimaging subtypes based on structural brain imaging features?
*Do these subtypes exhibit distinct biological signatures across multiple omics layers?
*Are subtype-specific biological profiles linked to differences in cognitive performance and long-term cognitive outcomes?
*Can an integrated neuroimaging-multiomics framework improve CKD cognitive impairment risk stratification?
Objectives:
*identify neuroimaging-based CKD subtypes with shared structural brain characteristics;
*characterize the molecular pathways underlying each subtype via UK Biobank multi-omics data;
*link subtype membership to cognitive performance and longitudinal clinical outcomes to inform future risk stratification and targeted interventions strategies.
Neuroimaging provides a quantitative intermediate phenotype that links systemic disease with cognitive outcomes. Recent large-scale studies have shown that structural brain imaging features capture meaningful heterogeneity in neurological and psychiatric disorders, and that subtypes based on neuroimaging can reveal biologically distinct disease entities. The integration of neuroimaging and multi-omics data can elucidate subtype specific molecular pathways. UK Biobank offers an opportunity to extend this framework to CKD.
We hypothesize CKD-related cognitive impairment involves multiple neuroimaging-defined subtypes, each driven by unique molecular mechanisms and linked to distinct cognitive trajectories. Identifying these subtypes and their biological underpinnings will advance understanding of kidney-brain interactions and guide targeted prevention.
