This paper is an example of a disease that may cause also cognitive decline related to iron overload in the brain. A good indication for almost physiological iron chelator!

The primary goal of the 201 study was to reduce iron in the brain. It happened, so 434 is gradually becoming a generally accepted iron chelator of the brain. In these kidney patients, you cannot use un-physiological iron chelators, 434 is the only possibility.

Just my opinion!!!

Brain Imaging Behav

. 2025 Feb 11.

doi: 10.1007/s11682-025-00976-0. Online ahead of print.

Regional high iron deposition on brain quantitative susceptibility mapping correlates with cognitive decline in chronic kidney disease patients

Yuan Li ^{# 1}, Yuhan Jiang ^{# 1 2}, Bingbing Gao ¹, Na Liu ¹, Yukun Zhang ¹, Huiling Zhou ³, Qingwei Song ¹, Nan Wang ⁴, Yanwei Miao ⁵

Affiliations Expand

• PMID: 39930019

DOI: 10.1007/s11682-025-00976-0

Abstract

This study aimed to evaluate changes in gray matter nuclei iron deposition in chronic kidney disease (CKD) patients using the quantitative susceptibility mapping (QSM) threshold method, and analyze the relationship between brain iron levels and cognitive function. A total of fifty-three CKD patients were prospectively recruited, comprising 35 hemodialysis (HD, 57.54 ± 10.42 years, 21 males) and 18 non-hemodialysis (NHD, 55.06 ± 11.47 years, 10 males ), and were compared to 43 healthy controls (HC, 55.67 ± 7.79 years, 18 males). All participants underwent clinical assessments, neuropsychological tests, and QSM scans. The mean magnetic susceptibility value (MSV) and volume of the whole nuclei (MSV_M, V_M) and high iron region (MSV_RII, V_RII) were measured. Correlations between QSM data, neuropsychological scores, and clinical variables in HD group were analyzed. Linear regression analysis was performed to explore the effect of iron deposition on cognition and emotional well-being in HD group. A statistically significant P-value was set at 0.05. HD patients exhibited higher MSV_M in the right red nucleus (RN) compared to HCs (P = 0.006). Additionally, significant differences in the MSV_RII were observed in the left caudate nucleus (CN), bilateral putamen (Put), and right RN among the three groups (all P = 0.027, FDR-corrected). MSV_RII of the left Put was positively correlated with creatinine and uric acid levels, while the MSV_RII of the right Put was negatively correlated with mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration. Regression analysis revealed that iron deposition in left CN was independently associated with depression, while iron deposition in left Put and right RN were independently positively associated with delayed recall performance. Conversely, iron deposition in bilateral Put and right RN were negatively associated with orientation ability, after controlling for age, sex, years of education and duration of dialysis. Brain iron deposition is often excessive and uneven in CKD patients, particularly those undergoing hemodialysis. Assessing regional high-iron deposition can provide valuable insights into the distribution of iron, which is associated with cognitive dysfunction and emotional disorders.