Advances in the study of the glymphatic system and diabetes-related cognitive dysfunction

Diabetes-related cognitive dysfunction (DCI) is a common central nervous system complication of diabetes mellitus; however, its pathogenesis remains poorly understood despite its significant clinical impact. The glymphatic system (GS), a waste clearance pathway in the brain, has been implicated in various central nervous system disorders. This review aims to systematically elaborate on the central role of the glymphatic system in DCI. We first summarize neuroimaging evidence of glymphatic system dysfunction in diabetes, including a reduced DTI-ALPS index and enlarged perivascular spaces. Furthermore, we examine its mechanisms, including dysregulated AQP4, impaired perivascular space function, and compromised drivers like arterial pulsation and sleep. Finally, we discuss the potential of glymphatic-targeted therapies, from lifestyle adjustments to pharmacological agents, for ameliorating DCI. This review emphasizes that glymphatic system dysfunction is a key link connecting diabetic metabolic disturbances to cognitive decline, offering a novel perspective and direction for research in this field.