Abstract
This review explores the complex relationship between neuroinflammation and cognitive decline in individuals with Type 2 Diabetes (T2D). There is increasing awareness that cognitive impairment, which can range from mild difficulties to severe dementia, is a significant complication associated with T2D. Extensive research indicates that chronic neuroinflammation plays a critical role in this context, linking metabolic dysfunction with neurodegenerative changes in the brain. The discussion begins with the effects of chronic hyperglycemia, insulin resistance, and metabolic disruptions that contribute to systemic inflammation. This inflammation can be intense enough to breach the blood-brain barrier (BBB), leading to neuroinflammation. The activation of essential immune cells in the brain, such as microglia and astrocytes, is accompanied by a rise in pro-inflammatory cytokines like IL-1β, IL-6, and TNF-α. These inflammatory agents disrupt synaptic function, inhibit neurogenesis, and promote neuronal death, particularly in areas critical for memory and executive functions, such as the hippocampus and prefrontal cortex. As the investigation unfolds, valuable insights are drawn from both preclinical and clinical studies. Animal research highlights the adverse effects of metabolic stress and inflammation on neuronal health, while clinical data correlate elevated inflammatory markers with reduced cognitive performance among individuals with T2D. Neuroimaging studies further support these findings by visually demonstrating microglial activation in regions essential for cognitive function.