# Structural Connectivity Disruption and Structural–Functional Decoupling in Working Memory Networks Across Pre‐Dialysis and Maintenance Hemodialysis End‐Stage Renal Disease Patients

## TL;DR

Pre-dialysis ESRD patients show disrupted brain connectivity and worse working memory, while hemodialysis patients show partial recovery.

## Contribution

Identifies structural and functional connectivity changes in ESRD patients and links them to serum markers and cognitive performance.

## Key findings

- Pre-dialysis ESRD patients had reduced frontoparietal structural connectivity and widespread SFC reductions.
- Elevated urea and lower sodium in pre-dialysis patients correlated with weaker connectivity and worse working memory.
- Maintenance hemodialysis patients showed near-normal working memory and partially restored connectivity.

## Abstract

End‐stage renal disease (ESRD) is associated with working memory (WM) impairment. We assessed how structural connectivity (SC), functional connectivity (FC), and structural–functional coupling (SFC) differ between pre‐dialysis ESRD (ESRDp), maintenance hemodialysis ESRD (ESRDm), and healthy controls (HCs), and how these changes relate to serum markers and WM performance.

29 ESRDp, 29 ESRDm, and 46 HCs completed 0‐, 1‐, and 2‐back tasks, diffusion MRI, and fMRI. WM nodes were defined by overlaying a meta‐analytic map with the Harvard–Oxford atlas. SC, FC, and regional SFC were computed among WM‐related regions. Group differences, correlations with serum markers, and mediation models were examined.

ESRDp showed markedly lower n‐back accuracy, longer reaction time (RT), reduced frontoparietal SC, and widespread SFC reductions compared with ESRDm and HCs, whereas ESRDm exhibited near‐normal WM performance and partially restored SC/SFC. Elevated urea and lower sodium in ESRDp were associated with weaker SC and altered SFC, which related to poorer accuracy and slower RT; SC and SFC significantly mediated these associations.

ESRDp is characterized by disruption and decoupling of WM networks, while ESRDm is associated with partial network normalization. WM‐related SC and SFC combined with serum markers may help identify cognitive vulnerability in ESRD.

ClinicalTrials.gov identifier: NCT03961724

This study examined structural connectivity (SC) and structural–functional coupling (SFC) within working memory (WM) networks in end‐stage renal disease. Pre‐dialysis patients showed disrupted frontoparietal connectivity and reduced coupling, associated with higher urea, lower sodium, and impaired WM performance. Maintenance hemodialysis patients exhibited near‐normal WM and partially restored network organization, suggesting WM‐related SC and SFC as indicators of cognitive vulnerability.