Research Progress on Pathology, Molecular Mechanisms, and Intervention Strategies of Cognitive Dysfunction Associated with Type 2 Diabetes.

Type 2 diabetes-associated cognitive dysfunction (DACD) is a major neurological complication of type 2 diabetes mellitus (T2DM). Against the backdrop of global population aging and the rising prevalence of T2DM, DACD poses a substantial challenge to public health. The pathogenesis of DACD involves the interplay of multiple signaling pathways and pathological processes, which remain incompletely understood. This review aims to systematically delineate the interconnections and regulatory networks among core mechanisms in DACD, including glucose transporter dysfunction, the oxidative stress-mitochondrial dysfunction-neuroinflammation axis, ferroptosis, the microbiota-gut-brain axis, autophagy, and epigenetic modifications. By integrating recent research advances in these mechanisms, this review provides a comprehensive understanding of the pathology of DACD and proposes multi-target intervention strategies from an integrated perspective, thereby offering insights for the development of future therapeutic approaches. This integrated framework is expected to provide new theoretical perspectives for clinicians and translational medicine researchers, to promote the development of diagnostic tools integrating multi-omics biomarkers, and to offer references for optimizing combination treatment strategies targeting key nodes across multiple mechanisms. The primary limitation of this review is that the conclusions are based predominantly on preclinical evidence; future clinical translation will require further validation through large-scale studies.