Cerebral white matter damage in patients with end stage kidney disease associates with cognitive impairment

Background and hypothesis Damages in brain white matter often occurs in individuals with chronic kidney disease, which might be related to their cognitive decline. This study aims to investigate tract specific white matter damage in patients with end stage renal disease by using fixel based analysis. Methods Images of 31 end stage renal disease patients and 16 normal controls (aged: 61.1 ± 10.4 years; 11 men) were acquired from a 1.5 T MR scanner. The patients were subsequently divided into with normal cognition (N = 17, aged: 66.9 ± 7.2 years; 10 men) and cognitive impairment (N = 14, aged: 72.4 ± 9.4 years; 7 men). Cognitive assessment, neurologic, hematologic and biochemical samples were collected. Fixel-based analysis was used to examine the tract-specific damage within white matter. Differences between groups were evaluated through connectivity-based fixel enhancement and non-parametric permutation testing. Correlation with biomarkers was conducted through general linear model. Significance was determined with familywise error-corrected p-value < 0.05. Results Reduced fixel-based metrics were observed in specific tract located the cerebral peduncle, internal capsule, corpus callosum, fornix, and superior corona radiata in patients when compared to normal controls, indicating a reduction in fiber content. The fibers crossing the corpus callosum and the fornix/stria terminalis are particularly vulnerable sites, which can be associated with the decrease in both Mini-Mental State Examination (R2 ranged between 0.420 and 0.556) and Montreal Cognitive Assessment (R2 ranged between 0.425 and 0.509), as well as the plasma concentration of calcium (R2 ranged between 0.207 and 0.322). The plasma concentration of indoxyl sulfate was associated with the descending tracts from right posterior limb of internal capsule to cerebral peduncle (R2 ranged between 0.262 and 0.335). Conclusions Tract specific white matter damage can be noticed in the patients with end stage renal disease, and can be associated with their cognitive decline.