Sex‐specific and Obesity‐specific Association of Serum Uric Acid with Cognitive Function in Older Adults

Abstract

Lower serum uric acid concentrations have been linked to cognitive dysfunction. Uric acid is an antioxidant that accounts for over half of the free radical scavenging activity in humans. Higher serum concentrations of uric acid have been associated with slower progression of several neurodegenerative diseases. On the other hand, elevated serum uric acid levels have been associated with poorer processing speed and executive functioning and greater white matter atrophy. Our aim in this study was to ascertain the relation between uric acid and cognitive function in older adults with mild cognitive decline (defined at 1–1.5 SD below the mean on the Montreal Cognitive Assessment, MoCA). Cognitive function was assessed using the MoCA and Cambridge Neuropsychological Test Automated Battery (CANTAB). Mean concentrations of serum uric acid in 107 individuals (mean age = 72.7 ± 4.3 years) were 5.9 ± 2.3 mg/dl; males had significantly higher uric acid concentrations (6.3 ± 1.1 mg/dl) compared to females (5.4 ± 1.1 mg/dl). Obese individuals’ concentrations were higher (6.2 ± 1.1 mg/dl) as compared to overweight (6.0 ± 1.1 mg/dl) and normal weight individuals (5.1 ± 1.2 mg/dl). Hyperuricemia (in males, serum uric acid > 7mg/dl and in females, serum uric acid > 6mg/dl) was present in 24% of the individuals. Compared with normouricemic individuals, hyperuricemic had significantly (p < 0.05) elevated serum triglyceride levels (122.1 ± 67 vs. 184.5 ± 152 mg/dl) and higher waist circumference (39.3 ±4 vs. 41.1 ± 3 in). Serum uric acid was positively correlated with BMI, waist circumference, serum creatinine, serum glucose, serum cholesterol ( p < 0.00001). Serum uric acid was negatively associated with MoCA scores (r2 = −0.23, p = 0.02). When stratified by sex, serum uric acid was positively associated with errors made on the CANTAB spatial working memory task (t = 2.6, p = 0.014) in men, but not in women. Similarly, when stratified by BMI, serum uric acid was positively associated with spatial working memory errors (t = 2.9, p = 0.013) and rapid visual processing errors (t = 3.0, p = 0.01) from the CANTAB in obese individuals but not in normal or overweight individuals. In summary, among older adults, higher serum uric acid concentrations are linked to poorer cognitive function in all individuals, poorer spatial working memory in men and obese individuals, and poorer processing in obese individuals compared to other groups. These findings indicate a potential role for serum uric acid concentrations in cognitive function in older adults.Support or Funding InformationThis research was funded by grants from the United States Department of Agriculture (2010‐2342‐02 and 2015‐2809‐01) to the first author and a small grant from the Nutrition Research Institute to the first and last authors.