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Objective  To explore the relationship among serum uric acid (SUA) levels in different states of disease, human cognition, and spontaneous brain activities by resting-state functional MRI (rs-fMRI).    Methods  We prospectively recruited 100 subjects (age 58 ± 11 years, 55 females) who underwent fasting blood sampling, cognitive tests and rs-fMRI scans. The subjects were divided into two groups by sex and each sex group was further stratified into three subgroups according to SUA level in different states of disease. The amplitude of low-frequency fluctuation (ALFF) method was applied to assess spontaneous brain activity among groups. Pearson’s correlation analysis was used to investigate the relationships between the mean ALFF values (mALFF) and cognitive tests.    Results  A total of 97 patients completed the study protocol successfully. Significant differences in age, education level, number connection test (NCT), and word fluency were observed among the three subgroups in males (all  P  < 0.05). Results of group-by-sex interaction were distributed in bilateral pallidum and putamen [voxel  P -value < 0.001, cluster  P -value < 0.05, Gaussian random field (GRF)-corrected]. The tendency of the SUA effect on mALFF was different in males and females, particularly in corresponding High SUA subgroups (that is pre-hyperuricemia, both  P  < 0.001). Among the male subjects, mALFF values of the bilateral pallidum and putamen negatively correlated with attention/executive function.    Conclusion  Our results suggest that elevated SUA levels have different effects on spontaneous brain activities and cognitive function in males and females. Males with pre-hyperuricemia and hyperuricemia are more susceptible to changes in spontaneous brain activities and lower neuropsychological assessment scores, particularly in word fluency tests and NCT, compared to females.

Uric Acid Has Different Effects on Spontaneous Brain Activities of Males and Females: A Cross-Sectional Resting-State Functional MR Imaging Study