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

Background: Damage to 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 kidney disease by using fixel-based analysis.

Methods: Images of 31 end-stage kidney disease patients and 16 normal controls (aged: 61.1 ± 10.4 years; 11 men) were acquired from a 1.5T magnetic resonance 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, and 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 family-wise error-corrected P-value <.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 with 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 kidney disease, and could be associated with their cognitive decline.