Uric Acid and Cognition: What Is the Connection?

Cognitive decline is one of the most frequent and disabling non motor features in ageing. The relationship between uric acid (UA) levels and cognitive impairment varies with dementia subtype. In this context, dysmetabolism, oxidative stress and neuroinflammation play a role in cognitive impairment and are all affected by UA. The mechanisms of neuroprotection against oxidative stresses include both the antioxidant activity against reactive oxygen species (ROS) and the induction of the gene expression of the antioxidant enzymes. On the other hand, hyperuricemia induces the production of ROS and inflammatory cytokines, leading to neuroinflammation and neurodegeneration. The increased brain gliosis could link neuroinflammation and dysmetabolism. Also the gender-related differences in the clinical features of cognitive impairment could be partly related to UA and should be taken into account for the `normal` range set for UA concentration. In conclusion, UA affects cognitive function, by interacting with neural, immune, cardiometabolic and, probably, adipose pathways and could be a target of the neuro-immune-adipose interactions.