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

Abstract

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. 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). 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. 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 μmol/L); each unit increment in SUA level reduced the MCI risk by 0.7% (p = 0.003). 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.