Unraveling the roles of anemia, renal impairment, and neuroinflammation in hemodialysis-associated cognitive dysfunction in chronic kidney disease patients

Background: The incidence of cognitive dysfunction (CD) is relatively high among patients with chronic kidney disease (CKD), and CD may be associated with anemia, deteriorating renal function, brain iron deposition (ID), and imbalances in neurocytokines. The purpose was to evaluate the changes in routine blood tests, renal function, cognitive function, brain ID, iron metabolism, and neurocytokines in patients with CKD-related CD. Methods: A retrospective analysis was conducted to compare differences in blood routine indicators, renal function indicators, Montreal Cognitive Assessment scale, brain iron deposition, iron metabolism indicators, and neurotrophic factors between hemodialysis patients with chronic kidney disease and cognitive impairment (observation group AG) and those without cognitive impairment (control group BG). Results: In contrast to the BG, the AG had significantly lower hemoglobin (Hb) levels; the AG had significantly higher creatinine (Cre) and uric acid (UA) levels, and a significantly lower estimated glomerular filtration rate (eGFR); the AG had significantly lower scores on the MoCA; the AG had significantly higher susceptibility values in the substantia nigra (SN), red nucleus (RN), globus pallidus (GP), and caudate nucleus (CN), and significantly lower susceptibility values in the putamen (PUT); the AG had significantly higher ferritin levels and significantly lower transferrin levels; the AG had significantly higher levels of neuron-specific enolase (NSE) and nerve growth factor (NGF), and significantly lower levels of brain-derived neurotrophic factor (BDNF; all p < 0.05). Conclusion: Chronic kidney disease-related cognitive dysfunction results from the synergistic effects of multiple physiological systems, including anemia, renal failure, brain iron metabolism disorders, and neuroinflammation-neurotrophic imbalance. Hemodialysis patients not only exhibit significant anemia and reduced glomerular filtration function but also show abnormal iron deposition in specific brain regions, accompanied by notable alterations in iron metabolism indicators and neurotrophic factor profiles.