Diabetes Mellitus-Dementia Correlate with Diabetic Management

Chaur-Jong HuTaiwan Speaker Diabetes Mellitus-Dementia Correlate with Diabetic ManagementDiabetes mellitus (DM) is a major metabolic disorder that substantially increases the risk of cognitive decline and dementia, including Alzheimer’s disease (AD) and vascular dementia. Growing evidence indicates that chronic hyperglycemia, insulin resistance, vascular injury, oxidative stress, and neuroinflammation are key mechanisms linking DM to neurodegeneration. Insulin resistance in the brain disrupts neuronal glucose utilization, enhances tau phosphorylation, and accelerates amyloid-β accumulation, while advanced glycation end-products (AGEs) and diabetes-related microvascular dysfunction further exacerbate neuronal injury. Effective diabetic management plays a critical role in mitigating dementia risk. Antidiabetic agents such as metformin, thiazolidinediones, and particularly glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated neuroprotective effects beyond glycemic control. GLP-1RAs improve insulin signaling, reduce neuroinflammation, enhance mitochondrial function, promote autophagy, and inhibit apoptosis, leading to preserved cognitive functions in preclinical models. Clinical studies show that GLP-1RAs may improve specific cognitive domains in patients with type 2 DM and reduce the incidence of cognitive impairment. However, the recent phase 3 trials, Eoke and Evoke+ failed to show the beneficial effects on AD. Overall, the strong interplay between DM and dementia highlights the necessity of optimal glycemic control and strategic use of antidiabetic therapies with neuroprotective potential. Integrating metabolic management into dementia prevention frameworks may offer an effective approach to reducing the global burden of cognitive disorders.