Genetic and circulating biomarkers of cognitive dysfunction and dementia in CKD
Carmine Zoccali, Francesca Mallamaci, Carsten A. Wagner, Robert J. Unwin, Maiken Nedergaard, Gaye Hafez, Jolanta Małyszko, Marion Pépin, Ziad A. Massy, Giuseppe Paolisso, Giuseppe Remuzzi, Giovambattista Capasso, CONNECT Action (Cognitive Decline in Nephro-Neurology European Cooperative Target) collaborators, Giovambattista Capasso, Alexandre Andrade, Mustafa Arici, Maie Bachmann, Matthew A. Bailey, Michelangela Barbieri, Mickaël Bobot, Annette Bruchfeld, Inga Arune-Bumblyte, Daiva Rastenytė, Antonello Calcutta, Giovanna Capolongo, Sol Carriazo, Michele Ceccarelli, Adrian Covic, Ananya De, Pilar Delgado, Nicole Endlich, Matthias Endres, Fabrizio Esposito, Michele Farisco, Quentin Faucher, Ana Carina Ferreira, Andreja Figurek, Denis Fouque, Casper Franssen, Ivo Fridolin, Sebastian Frische, Liliana Garneata, Loreto Gesualdo, Konstantinos Giannakou, Olivier Godefroy, Aleksandra Golenia, Dimitrios Goumenos, Eugenio Gutiérrez Jiménez, Gaye Hafez, Ewout J. Hoorn, Pedro Henrique Imenez Silva, Raafiah Izhar, Dearbhla Kelly, Shelli R. Kesler, Aleksandra Klimkowicz‐Mrowiec, Samuel Knauß, Justina Kurganaite, Hélène Levassort, Sophie Liabeuf, Jolanta Małyszko, Laila‐Yasmin Mani, Gianvito Martino, Ziad A. Massy, Christopher Mayer, Armida Mucci, Alma Mutevelić-Turković, Rikke Nielsen, Dorothea Nitsch, Alberto Ortíz, Vasileios Panagiotopoulos, Despoina Karasavvidou, Giuseppe Paolisso, Bojana Pejušković, Marion Pépin, Alessandra Perna, Andrea Perrottelli, Vesna Pešić, Pasquale Pezzella, Merita Rroji, Ivan Rychlík, Giorgos K. Sakkas, Mariadelina Simeoni, María José Soler Romeo, Goce Spasovski, Ana Starčević, Gioacchino Tedeschi, Francesco Trevisani, Robert J. Unwin, Evgueniy Vazelov, Carsten A. Wagner, Franca Wagner, Christoph Wanner, Andrzej Wiecek, Hong Xu, Miriam Zacchia, Lefteris Zacharia, Irene Zecchino, Carmine Zoccali, Francesco Mattace‐Raso, Karlhans Endlich
Abstract
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.