Metabolic Dysfunction and Brain Health: Diabetes as a Risk Factor for Dementia

Jong-Ling FuhTaiwan Speaker Metabolic Dysfunction and Brain Health: Diabetes as a Risk Factor for DementiaType 2 Diabetes Mellitus (T2DM) is no longer confined to glucose dysregulation—it is a systemic accelerator of brain aging and a major modifiable risk factor for dementia. Epidemiologic and mechanistic studies reveal that poor glycemic control, including both hyper- and hypoglycemia, significantly increases dementia risk. Data from Taiwan’s National Health Insurance Database show that pronounced glycemic fluctuations more than double this risk, while meta-analyses identify prolonged diabetes duration, elevated HbA1c, hypertension, and insulin resistance as key predictors of cognitive decline. Pathophysiological evidence links chronic hyperglycemia and insulin resistance to neuroinflammation, oxidative stress, and tau pathology. Neuroimaging studies show hippocampal atrophy and white matter degradation in patients with poorly controlled diabetes. Cardiovascular comorbidities amplify this burden: diabetes combined with coronary artery disease doubles the risk of vascular dementia. Encouragingly, therapeutic innovation offers hope. Glucose-lowering agents such as GLP-1 Receptor Agonists (GLP-1RAs) and SGLT2 Inhibitors (SGLT2is) may extend their cardiometabolic benefits to the brain. GLP-1RAs have shown a 45% reduction in dementia risk in real-world and trial-based analyses, reinforcing the interconnectedness of metabolic, vascular, and neurodegenerative pathways. In East Asia, where diabetes and dementia are surging, the clinical imperative is clear: brain health must be a core outcome of metabolic care. Early glycemic optimization, vascular protection, and neuroprotective therapies may define the next frontier in dementia prevention.