The Vicious Consequences of Chronic Kidney Disease on Cognitive Impairment and Alzheimer’s Disease

Chronic kidney disease (CKD) and Alzheimer's disease (AD) are two prevalent and debilitating conditions that frequently coexist, with CKD contributing to cognitive decline and potentially exacerbating AD pathology. In CKD, irreversible changes in the structure or function of the kidneys are observed, while AD is primarily marked by amyloid deposition and tau pathology. Both conditions involve complex and multifactorial pathophysiology affecting brain functioning, highlighting the need for comprehensive research to understand their potential crosstalk. This review articulates the possible molecular mechanisms underlying both diseases, focusing on key pathways, including oxidative stress, inflammation, vascular dysfunction, hypertension, and uremic toxin accumulation. These interconnected mechanisms suggest a potential bidirectional relationship where kidney dysfunction accelerates cognitive decline and vice versa. Additionally, we examine critical risk factors implicated in both CKD and AD, for instance, vitamin D deficiency, erythropoietin dysregulation, endothelin action, klotho gene expression, and the role of the extracellular vesicle, which may influence disease progression through their effects on the kidney and brain, influencing cognitive function. Further, we emphasized potential biomarkers that could aid in diagnosing and monitoring disease progression in these comorbid conditions, like amyloid beta, tau, homocysteine, cystatin C, creatinine, proteinuria, and estimated glomerular filtration rate. Lastly, the review highlights treatment strategies for managing CKD and AD concurrently, focusing on therapeutic approaches that address common pathophysiological mechanisms. These strategies not only aim to address the underlying causes of both conditions but also offer the potential to slow or even prevent the progression of cognitive impairment. Moreover, we recommend further research to refine these approaches, execute correlational studies on disease progression, and design clinical trials that address both conditions, aiming to establish effective, tailored treatments for this dual burden of disease.