Cognitive deterioration in patients undergoing hemodialysis: how variations in age influence the development of new mechanisms and treatment approaches?

Abstract

The mechanisms of age-related differences and innovative intervention strategies for cognitive dysfunction in hemodialysis patients are crucial for enhancing patient outcomes. This research thoroughly examined the varying pathological aspects of cognitive decline across different age groups. Children and adolescents experience heightened permeability of the blood-brain barrier during critical developmental phases, along with the disruptive effects of uremic toxins on neurotransmitters and synaptic plasticity, which result in diminished white matter integrity and abnormal functioning of the default mode network. Additionally, genomic variations, such as harmful CNVs, coexist with the central nervous system's high plasticity and susceptibility. In contrast, elderly patients face cognitive impairment due to the combined effects of vascular diseases (like small vessel disease and impaired cerebral blood flow regulation) and Alzheimer's-like pathology, exacerbated by dialysis-related hypotension, oxidative stress, and inflammation, which further contribute to reduced cerebral blood flow and neurodegeneration. Consequently, a life cycle-based layered intervention strategy is suggested: children should focus on safeguarding their neural development through collaborative gene-environment interventions and neural stem cell transplants, while elderly patients require standardized treatment for vascular diseases and comorbidities, including Alzheimer's disease. Evidence indicates that incremental dialysis, low temperature dialysis, and high-dose hemodiafiltration can significantly reduce inflammation and oxidative stress markers, slow cognitive decline across all ages, and offer new insights for targeted nephrology management due to their universal effects. Future multi-center cohort studies are necessary to confirm the long-term advantages of age-specific interventions and to support the development of personalized precision treatment systems.