Background: Cognitive impairment is a prevalent complication of type 2 diabetes, influenced significantly by various dietary patterns. High-carbohydrate diets (HCDs) are commonly consumed nowadays; however, the specific impact of HCDs on cognitive function in diabetes remains unclear. Methods: The objective of this study was to investigate whether an HCD has effects on cognition in diabetes. Eight-week-old diabetic (db/db) mice and wild-type (WT) mice underwent a twelve-week dietary intervention, including a normal diet (ND), an HCD, or a high-fat diet (HFD). Following this, behavioral tests were conducted, and related hippocampal pathology was evaluated. Results: Our results demonstrated that an HCD exacerbated cognitive decline in db/db mice compared to an ND. Additionally, an HCD increased amyloid-β burden and expression of β-site APP cleaving enzyme-1. An HCD was also found to promote the phosphorylation of tau protein via the PI3K/Akt/GSK-3β pathway. Furthermore, an HCD markedly induced neuroinflammation and increased the quantity of microglia and astrocytes. However, these damages induced by an HCD were less severe than those caused by an HFD. Conclusions: Collectively, our findings indicate that a high intake of carbohydrates can have an adverse impact on cognitive function in diabetes.
