Susceptibility alterations in the hippocampus and subcortical nuclei in hemodialysis patients with end-stage renal disease: an APART-QSM study

Objective To investigate APART-QSM-derived paramagnetic susceptibility (χpara) alterations in hippocampal, medial temporal, and subcortical regions in maintenance hemodialysis patients with end-stage renal disease (ESRD). Methods This cross-sectional study included 55 maintenance hemodialysis patients with ESRD and 39 healthy controls. χpara, the primary imaging outcome, was extracted from FreeSurfer-defined bilateral hippocampal, medial temporal, and subcortical regions. Group differences across 20 prespecified ROIs were tested using age- and sex-adjusted linear models. Hippocampal sensitivity models additionally included ipsilateral hippocampal volume and estimated total intracranial volume (eTIV). Correlations within the ESRD group were exploratory. Multiple comparisons were controlled using the Benjamini-Hochberg false discovery rate (FDR). Results After adjustment for age, sex, and education, patients with ESRD had lower MMSE, MoCA total, and MoCA delayed recall scores than controls. χpara was higher in the bilateral hippocampus (left: β = 0.002855 ppm, 95% CI: 0.001531–0.004179 ppm, q < 0.001; right: β = 0.002102 ppm, 95% CI: 0.000893–0.003312 ppm, q = 0.008), left putamen ( β = 0.007775 ppm, 95% CI: 0.002329–0.013222 ppm, q = 0.023), and bilateral ventral diencephalon (left: β = 0.005427 ppm, 95% CI: 0.002029–0.008825 ppm, q = 0.014; right: β = 0.004935 ppm, 95% CI: 0.001483–0.008386 ppm, q = 0.023). Bilateral hippocampal χpara remained nominally significant after adjustment for ipsilateral hippocampal volume and eTIV. Supplementary analyses showed lower χdia magnitude in the left hippocampus, higher χdia magnitude in the bilateral caudate, and higher APART total susceptibility in the bilateral hippocampus, left putamen, and bilateral VentralDC after metric-specific FDR correction. No associations between ROI-wise susceptibility metrics and cognitive scores survived FDR correction. Conclusion Maintenance hemodialysis patients with ESRD showed increased χpara in the bilateral hippocampus, left putamen, and bilateral VentralDC. Supplementary source-separated metrics showed additional regional differences, but their algebraic relationship and nonspecific biological origins require cautious interpretation.