Translational research on cognitive impairment in chronic kidney disease
Authors: Wagner Carsten A , Massy Ziad A , Capasso Giovambattista , Mattace-Raso Francesco , Pepin Marion , Bobot Mickaël , Zoccali Carmine , Ferreira Ana C , Hoorn Ewout J , Imenez Silva Pedro H , Unwin Robert J , Pesic Vesna ,   CONNECT, Capasso Giovambattista , Andrade Alexandre , Arici Mustafa , Bachmann Maie , Bailey Matthew , Barbieri Michelangela , Bobot Mickaël , Bruchfeld Annette , Arune-Bumblyte Inga , Rastenytė Daiva , Calcutta Antonello , Capolongo Giovanna , Carriazo Sol , Ceccarelli Michele , Covic Adrian Constantin , De Ananya , Delgado Pilar , Endlich Nicole , Endres Matthias , Esposito Fabrizio , Farisco Michele , Faucher Quentin , Ferreira Ana Carina , Figurek Andreja , Fouque Denis , Franssen Casper , Fridolin Ivo , Frische Sebastian , Garneata Liliana , Gesualdo Loreto , Giannakou Konstantinos , Godefroy Olivier , Golenia Aleksandra , Goumenos Dimitrios , Jiménez Eugenio Gutiérrez , Hafez Gaye , Hoorn Ewout , Silva Pedro Henrique Imenez , Izhar Raafiah , Kelly Dearbhla , Kesler Shelli , Klimkowicz-Mrowiec Aleksandra , Knauss Samuel , Kurganaite Justina , Levassort Hélène , Liabeuf Sophie , Malyszko Jolanta , Mani Laila-Yasmin , Martino Gianvito , Massy Ziad , Mayer Christopher , Mucci Armida , Mutevelic-Turkovic Alma , Nielsen Rikke , Nitsch Dorothea , Ortiz Alberto , Panagiotopoulos Vasileios , Karasavvidou Despoina , Paolisso Giuseppe , Pejušković Bojana , Pepin Marion , Perna Alessandra , Perrottelli Andrea , Pešić Vesna , Pezzella Pasquale , Rroji (Molla) Merita , Rychlík Ivan , Sakkas Giorgos , Simeoni Mariadelina , Romeo Maria José Soler , Spasovski Goce , Starčević Ana , Tedeschi Gioacchino , Trevisani Francesco , Unwin Robert , Vazelov Evgueniy , Wagner Carsten Alexander , Wagner Franca , Wanner Christoph , Wiecek Andrzej , Xu Hong , Zacchia Miriam , Zacharia Lefteris , Zecchino Irene , Zoccali Carmine , Mattace-Raso Francesco , Endlich Karl-Hans , Perico Norberto , Remuzzi Giuseppe , Trepiccione Francesco , Okusa Mark , Marzo Vincenzo Di , Blankestijn Peter , Eckardt Kai-Uwe , Konig Maximilian , Gansevoort Ron , Askari Hassan , Hansen Brian , Snaedal Sunna , Cuiban Elena , Caporusso Edoardo , Re Vincenzina Lo , Roiser Jonathan , Rosenberg Kerry , Bisecco Alvino , Denby Laura , Kulkarni Onkar Prakash , Sharma Kumar , Debnath Subrata , Jaafar Afaf , Capasso Anna , Mulholland Michele , Workeneh Biruh , Iervolino Anna , Fraser Simon , Frey-Wagner Isabelle , Pastore Annachiara , Mačiulaitis Romaldas , Farinha Ana 
Published: October 2024

ABSTRACT
Cognitive decline is common in patients with acute or chronic kidney disease. Several areas of brain function can be affected, including short- and long-term memory, attention and inhibitory control, sleep, mood, eating control and motor function. Cognitive decline in kidney disease shares risk factors with cognitive dysfunction in people without kidney disease, such as diabetes, high blood pressure, sedentary lifestyle and unhealthy diet. However, additional kidney-specific risk factors may contribute, such as uremic toxins, electrolyte imbalances, chronic inflammation, acid–base disorders or endocrine dysregulation. Traditional and kidney-specific risk factors may interact to cause damage to the blood–brain barrier, induce vascular damage in the brain and cause neurotoxicity or neuroinflammation. Here, we discuss recent insights into the pathomechanisms of cognitive decline from animal models and novel avenues for prevention and therapy. We focus on a several areas that influence cognition: blood–brain barrier disruption, the role of skeletal muscle, physical activity and the endocrine factor irisin, and the emerging therapeutic role of sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists. Taken together, these studies demonstrate the importance of animal models in providing a mechanistic understanding of this complex condition and their potential to explain the mechanisms of novel therapies.