Association of Iron Status With Global and Domain-Specific Cognitive Function in Patients With Non-Dialysis Chronic...

Cognitive impairment is prevalent in patients with chronic kidney disease (CKD) and may be exacerbated by iron deficiency through impaired oxygen delivery and disrupted neuronal metabolism. However, no prior study has specifically examined the role of iron status in cognitive function among patients with nondialysis CKD. This study aimed to investigate the associations of iron status markers (serum iron, transferrin saturation [TSAT], and ferritin) as well as hemoglobin with cognitive performance in CKD stages 3-5. We conducted a cross-sectional study of 147 patients with nondialysis CKD [median age 66.0 (57.0-72.0) years; median estimated glomerular filtration rate 23.0 (13.5-33.2) mL/min/1.73 m²]. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE). Mild cognitive impairment (MCI) was defined as MoCA scores ≤23 or MMSE scores ≤26. Associations between iron markers and cognitive scores were analyzed using linear and logistic regression models, adjusted for age, sex, education, comorbidities (diabetes, hypertension, and cardiovascular disease), physical activity, estimated glomerular filtration rate, use of erythropoiesis-stimulating agents, Z-drugs, and hemoglobin. Patients with MCI were older, had lower education levels, and exhibited reduced serum iron, TSAT, and physical activity. Higher serum iron and TSAT levels were independently associated with better MoCA and MMSE scores and lower odds of MCI. Domain-specific analyses revealed that serum iron and TSAT were positively associated with MoCA attention and abstraction domains, and MMSE orientation and attention/calculation domains. No consistent associations were observed for ferritin, and hemoglobin was not significantly associated with cognitive outcomes after adjustment. In nondialysis CKD stages 3-5, higher serum iron and TSAT levels were independently associated with better global and domain-specific cognitive function, regardless of hemoglobin status. These findings suggest a potential role for iron status in modulating cognitive health in CKD, meriting further longitudinal and interventional studies.