Uric Acid and Lead in Cognition and Mental Health

Abstract

Oxidative stress has been found to play an important role in the pathogenesis of cognitive decline, and emerging evidence also suggest the involvement of oxidative stress in psychiatric disorders. These findings have raised the potential for antioxidants to have beneficial influences on cognition and mental health. Uric acid, the final product in the metabolism of purines, is one particular antioxidant that has been associated with neuroprotection in several neurodegenerative conditions. We first revisited the association between serum uric acid and cognitive function in the Normative Aging Study and examined factors that could have contributed to the inconsistent findings from previous studies, including specific exposure windows for uric acid, differences in cognitive outcomes, and the role of cardiovascular health. As lead exposures can induce oxidative stress and has been associated with cognitive decline and psychological disorders in adults, we evaluated whether uric acid could modify the associations between lead exposures and cognitive changes over time and psychological disorders. Cognitive outcomes and psychological symptoms were assessed using established instruments; cumulative biomarker measures of lead were assessed in the tibia and patella bone and recent biomarker measure of lead was assessed in the blood. We did not find a clear association between uric acid and cognitive function, but found that uric acid modified the associations between lead exposures and cognitive decline and psychological symptoms such that the adverse associations were less pronounced at higher levels of uric acid. These results suggest that strategies involving antioxidants could potentially mitigate the detrimental effects of lead exposures on cognitive decline and psychological symptoms.