Mind the Gut: Cognitive Decline, Microbiota, and Nutrition-Related Modulators in Older Adults with Chronic Kidney Disease

Chronic kidney disease (CKD) is a progressive condition characterized by persistent kidney abnormalities with systemic consequences. Beyond its metabolic and cardiovascular complications, CKD has been associated with structural and functional brain alterations that are particularly evident in advanced stages and in patients undergoing hemodialysis (HD). Deficits across multiple cognitive domains are frequently observed and may compromise treatment adherence, clinical management, and quality of life, yet remain largely underrecognized in clinical practice. Older adults are particularly vulnerable. Age-related brain changes and comorbidities may increase susceptibility to CKD-related cerebral alterations, while reduced cognitive reserve may amplify clinical impact. The gut–kidney–brain axis has emerged as a relevant biological pathway, with CKD-related dysbiosis potentially influencing inflammation, metabolic homeostasis, and the generation of uremic metabolites linked to neurological dysfunction. This review examines the mechanisms contributing to brain vulnerability in older adults with CKD, with specific attention to patients undergoing HD, and discusses challenges in the recognition and assessment of cognitive impairment in this population. It further explores microbiota-targeted nutritional strategies as potentially modifiable approaches to modulate gut-derived metabolic and inflammatory processes relevant to brain health, although current evidence for direct effects on cognitive outcomes remains limited.