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

AIMS: 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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03961724.