HSPA5 and Cognitive impairment: Research has shown that the abnormal accumulation of advanced glycation end-products (AGEs) due to hyperglycemia increases the production of reactive oxygen species (ROS), which in turn activates downstream APP-related pathways, enhances Aβ production, and upregulates NAD + -dependent deacetylase sirtuin 1 (Sirt1) and glucose-regulated protein 78 (GRP78), leading to neuronal cell death pathways and ultimately contributing to the onset of cognitive impairments (Kong et al., 2020).