Diabetes Mellitus and Cognitive Decline: A Systematic Review Exploring the Link to Dementia and Neurodegenerative Diseases

Abstract

This systematic review explores the association between diabetes mellitus (DM) and cognitive decline, with a particular focus on neurodegenerative diseases such as dementia and Alzheimer's disease (AD). A comprehensive search strategy, conducted in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, identified and selected nine meta-analyses of high relevance and methodological rigor. These studies encompassed diverse populations, including stroke survivors, apolipoprotein E (APOE) ɛ4 carriers, and individuals with metabolic syndrome, and examined both interventions, such as glucose-lowering therapies, and risk factors, including hypoglycemia and poor glycemic control. Key findings indicate that diabetes is a significant risk factor for cognitive decline, with strong associations observed between impaired glucose metabolism and elevated tau biomarkers. Glucose-lowering therapies, particularly sodium-glucose cotransporter-2 (SGLT-2) inhibitors and metformin, demonstrated potential neuroprotective effects, reducing the risk of dementia and cognitive impairment. However, heterogeneity among the studies and variability in study designs highlight the need for further high-quality research to validate these findings and elucidate underlying mechanisms. This review underscores the importance of integrating cognitive health into diabetes management and highlights the potential of targeted interventions to mitigate the cognitive burden associated with diabetes.