Chronic kidney disease as a natural model of accelerated cognitive ageing: mechanisms and novel therapeutic directions"
Year: 2026
Type: article
Abstract: Cognitive impairment is common in chronic kidney disease (CKD), affecting approximately 40% of patients and increasing sharply as kidney function declines. CKD accelerates many pathophysiological mechanisms shared with brain ageing, with implications for, rather than any equivalence to, the neurodegenerative diseases associated with dementia, notably Alzheimer’s disease and Lewy body dementia. Furthermore, CKD introduces distinct injuries that further amplify these pathways. The convergent mechanisms include cerebral small vessel disease, chronic neuroinflammation, blood-brain barrier (BBB) disruption, accumulation of neurotoxic uraemic solutes, gut-brain-kidney axis dysbiosis, and impaired glymphatic clearance; superimposed on these, haemodialysis imposes repeated episodes of acute cerebral haemodynamic stress. Recent evidence also highlights the kidney’s failure to clear circulating aggregation-prone proteins, such as amyloid-β and α-synuclein. Because these processes develop earlier and progress more rapidly in CKD than in the general ageing population, they effectively create a ‘time-compressed’ version of age-related cognitive decline. In this review, we propose reconceptualising CKD as a prevalent clinical model of accelerated cognitive decline. We examine converging evidence from epidemiology, neuroimaging, and molecular studies to support this hypothesis. Finally, we discuss how emerging therapies—ranging from targeted adsorbents and Klotho replacement to microbiome modulation and preventive immunology—are testable hypotheses in CKD, with possible relevance for dementia in the wider ageing population.
Source: Clinical Kidney Journal
DOI: 10.1093/ckj/sfag392
Institutions: University of Campania "Luigi Vanvitelli", Biogem, Alexandria University, University College London, Instituto de Investigación Biomédica de Lleida, Koç University, Università Cattolica del Sacro Cuore, Agostino Gemelli University Polyclinic, Universidad de La Laguna, Instituto de Salud Carlos III, Hospital Universitario Nuestra Señora de Candelaria, Linköping University, Karolinska Institutet, Erasmus MC, Universitätsklinikum Aachen, RWTH Aachen University, University Medical Center Utrecht, University of Birmingham, University of Liège, Université de Montpellier, Centre Hospitalier Universitaire de Liège
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,335
OpenAlex ID: W7225261727