U-Shaped Association Between Serum Uric Acid Levels and Cognitive Functions in Patients with Type 2 Diabetes: A Cross-Sectional Study

Background: Serum uric acid (SUA) is a natural antioxidant that may exert neuroprotective effects against neurodegenerative diseases. The relationship between uric acid and cognitive functions has been extensively studied, but results remain conflicting. Objective: To investigate potential associations between SUA level and mild cognitive impairment (MCI), and different domains of cognitive performances in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 352 T2DM subjects (208 males and 144 females) were enrolled. SUA level was determined by using the uricase method. Cognitive performances were assessed using a validated neuropsychological test battery. Generalized additive models and binary logistic regression analysis were fitted to determine the association between SUA and cognitive functions. Results: A total of 157 T2DM patients had MCI, and 195 displayed normal cognition. Compared with the controls, MCI patients exhibited lower SUA level (p = 0.009). Generalized additive models revealed a U-shaped curve relationship among SUA with Montreal Cognitive Assessment, Auditory Verbal Learning Test-immediate recall and Trail Making Test-B scores (all p < 0.05). Further logistic regression analysis showed a significant trend toward decreased MCI risk with increased SUA level among the subjects whose SUA level was below the cut-point (388.63 mu mol/L); each unit increment in SUA level reduced the MCI risk by 0.7% (p = 0.003). Conclusion: A U-shaped association between SUA level and global cognitive function, especially executive and memory function, existed in T2DM patients. Our findings will provide additional suggestions that an increase of SUA to a certain level may be a novel method to reduce the burden of T2DM-associated cognitive impairment.