Cognitive impairment in chronic kidney disease: mechanisms, clinical manifestations, and management strategies

Abstract

Subjects with chronic kidney disease (CKD) are at higher risk for various neurological disorders, including dementia, depression, and sleep disturbances, all of which can influence disease progression and clinical outcomes. Cognitive impairment is often linked to renal decline, with the severity of cognitive deficits increasing in parallel with a reduction in glomerular filtration rate (GFR). For patients undergoing dialysis, the risk of moderate to severe cognitive impairment is significantly elevated. A central, unifying hypothesis proposes that the brain and kidneys share a similar microvascular architecture, making both organs highly susceptible to vascular injury. In this review, we make explicit two complementary mechanisms within this framework: (i) a common-cause model in which shared systemic risk factors (such as hypertension, diabetes, inflammation) concurrently damage renal and cerebral small vessels, and (ii) a CKD-mediated causal pathway whereby kidney dysfunction and its treatments propagate downstream neurovascular injury (uremic toxins, endothelial dysfunction and blood-brain barrier changes, anemia/hypoxia, metabolic and mineral disturbances, and dialysis-related hemodynamic stress), increasing the risk of cognitive impairment. We synthesize the current evidence on these mechanisms, outline the epidemiological patterns and clinical manifestations of cognitive decline in CKD, and discuss prevention, early diagnosis, and multidisciplinary management strategies aimed at improving outcomes in this vulnerable population.

Keywords: CKD; Cognitive impairment; Dementia; Dialysis; Uremic toxins.