Chronic Kidney Disease (CKD) is a global health challenge which affects around 10% of adults, and the prevalence of cognitive impairments in this population ranges from 30% to 60%. De facto, there is no validated intervention to counter mild cognitive impairment (MCI) in advanced CKD. Furthermore, knowledge of genetic and circulating biomarkers for cognitive impairment in CKD is very limited.

The project is based on 1) a 26 week randomized clinical trial (RCT) with a 78 week post-trial observation to evaluate the efficacy of a structured physical exercise program on cognitive function in advanced (stage G4-5) CKD and dialysis patients with mild cognitive impairment (MCI). 2) Analyses on circulating and genetic biomarkers available in the UK biobank database. Participants in the clinical trial will be divided into two groups: a control group receiving standard care along international guidelines on nutrition and risk factors management in CKD and an intervention group receiving the same care and a tailored exercise program.

The main outcome measure will be the change in cognitive function, assessed by the Alzheimer Disease Assessment Scale Cognitive 13 (ADAS-Cog-13) and the Plus variant. The trial will enrol 124 patients (62 per study arm) with an 80% power to detect an effect size of 0.40 (standard deviation: 0.60) in ADAS-Cog3 at a 2-sided, 5% significance level. The UK Biobank is a comprehensive, publicly available research resource. About 5000 individuals in this Biobank have CKD. Analyses in this biobank will test the cross-sectional and longitudinal association of physical exercise with cognitive function, circulating and genetic biomarkers of cognitive function, and brain MRI in individuals with and without CKD. By identifying an effective intervention and biomarkers for cognitive decline in CKD patients, this research could pave the way for better clinical practices and improved outcomes for a population at high risk of cognitive impairment.