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    Genetic and circulating biomarkers of cognitive dysfunction and dementia in CKD
    (2025) Zoccali, Carmine; Mallamaci, Francesca; Wagner, Carsten A.; Unwin, Robert; Nedergaard, Maiken; Hafez, Gaye; Malyszko, Jolanta; Pepin, Marion; Massy, Ziad; Paolisso, Giuseppe; Remuzzi, Giuseppe; Capasso, Giovambattista B.; CONNECT Action (Cognitive Decline in Nephro-Neurology European Cooperative Target) collaborators
    Chronic kidney disease (CKD) is commonly accompanied by cognitive dysfunction and dementia, which, in turn, increase the risk of hospitalization, cardiovascular events and death. Over the last 30 years, only four studies focused on genetic markers of cognitive impairment in CKD and kidney failure (KF), indicating a significant gap in research. These studies suggest potential genetic predispositions to cognitive decline in CKD patients but also underscore the necessity for more comprehensive studies. Seventeen reports have established connections between cognitive function and kidney disease markers such as estimated glomerular filtration rate (eGFR), Cystatin C and albuminuria. A rapid eGFR decline has been associated with cognitive deterioration and vascular dementia, and mild to moderate eGFR reductions with diminished executive function in elderly men. Various biomarkers have been associated to Alzheimer’s disease or dementia in CKD and KF. These include amyloid beta and phosphorylated tau proteins, uremic toxins, gut microbiota, metabolic indicators, hypertension, endothelial dysfunction, vitamins and inflammation. However, the causal relevance of these associations remains unclear. Overall, the available evidence points to a complex interplay between the different biomarkers and cognitive health in CKD patients, underscoring the need for more research to elucidate these relationships.