Longitudinally altered default mode network and insula multimodal brain pattern in end-stage renal disease during...

Hemodialysis (HD) is the predominant treatment for end-stage renal disease (ESRD). Despite the efficacy of HD, the neurobiological underpinnings underlying high-risk complications remain unclear. In this study, using unsupervised fusion of functional and structural MRI, we identified a longitudinally altered default mode network (DMN)-insula pattern in ESRD receiving HD over 1-year follow-up (n = 39). This pattern was associated with cognition, and its related genes were enriched in biological processes involving DNA damage and repair, energy metabolism, and cellular activation. The baseline DMN-insula pattern demonstrated potential predictive value for follow-up cognition in ESRD. More importantly, these brain-cognition associations were validated in independent high-risk complications cohorts, including major depressive disorder (n = 60), mild cognitive impairment (n = 291), and Alzheimer's disease (n = 77) by extracting the corresponding brain features and assessing their correlations with cognition. Collectively, this study may help researchers better understand the underlying mechanisms of ESRD receiving HD from a multimodal neuroimaging and molecular perspective.