Dysfunctional Coupling of Cerebral Blood Flow and Susceptibility Value in the Bilateral Hippocampus is Associated with Cognitive Decline in Nondialysis Patients with CKD

Abstract

Background: Cerebral blood flow (CBF) and susceptibility values reflect vascular and iron metabolism, providing mechanistic insights into conditions of health and disease. Non-dialysis patients with chronic kidney disease (CKD) show a cognitive decline, but the pathophysiological mechanisms underlying this remain unclear. Methods: Three-dimensional pseudo-continuous arterial spin labeling and quantitative susceptibility mapping were prospectively performed in 40 patients with stage 1–4 CKD (CKD 1–4), 47 non-dialysis patients with stage 5 CKD (CKD 5ND), and 44 healthy controls. Voxel-based global and regional analyses of CBF, susceptibility values, and vascular-susceptibility coupling were performed. Furthermore, the association between clinical performance and cerebral perfusion and iron deposition was analyzed. Results: For CBF, patients with CKD 5ND had higher normalized CBF in the hippocampus and thalamus than healthy controls. Patients with CKD 5ND had higher normalized CBF in the hippocampus and thalamus than those with CKD 1–4. The susceptibility values in the hippocampus and thalamus were lower in patients with CKD 5ND than in healthy controls. Patients with CKD 5ND had higher susceptibility value in the caudate nucleus than those with CKD 1–4. More importantly, patients with CKD 5ND had lower CBF-susceptibility coupling than healthy controls. Additionally, CBF and susceptibility values were significantly associated with clinical performance. Conclusions: Our findings demonstrate a new neuropathological mechanism in patients with CKD, which leads to regional changes in CBF-susceptibility coupling. These changes are related to cognitive decline, providing potential imaging markers for assessing clinical disability and cognitive decline in these patients.

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

“…Several studies have found brain iron overload of hemodialysis patients, with iron deposition in the basal ganglia being the most signi cant (Chai et al, 2014;Wang et al, 2020;Hao Wang et al, 2022). A recent analysis also showed that brain iron deposition increased in non-dialysis CKD patient (Wang et al, 2023). The mechanism of brain iron concentration in CKD patients is not completely clear.…”

Cognitive Impairment and Brain Atrophy in Patients with Chronic Kidney Disease

“…In Japan, which is rapidly moving towards a hyper-aged society, the number of patients with cognitive impairment (CI) is increasing rapidly, along with the number of those with chronic kidney disease (CKD) [ 1 , 2 , 3 ]. In recent years, it has become evident that CKD patients have a higher frequency of CI, and various studies have been conducted to explore the mechanisms, relationships, and strategies concerning CKD and CI [ 4 , 5 , 6 , 7 , 8 ]. Although many findings have been presented, numerous problems remain unresolved [ 9 , 10 , 11 ].…”