Sex-Dependent Associations of Serum Uric Acid with Brain Function During Aging

Abstract

Serum uric acid (SUA) is an abundant natural antioxidant capable of reducing cellular oxidation, a major cause of neurodegenerative disease. In line with this, SUA levels are lower in Alzheimer’s disease; however, the association between SUA and cognition remains unclear. Results from studies examining the effects of SUA on cognition may be difficult to interpret in the context of normal versus pathological aging. This study examined sex-specific associations of baseline SUA with cognition during aging. Data from dementia-free participants initially aged 26–99 (N = 1,451) recruited for the Baltimore Longitudinal Study of Aging (BLSA), were used in the current analyses. SUA was assessed using blood samples collected during research visits. Cognition was measured using five composite scores (verbal memory, attention, executive function, language, and visuospatial ability). At the first study visit, compared with women, men were older, more likely to be White, had more years of education, higher baseline SUA levels, and higher cardiovascular risk scores. Higher baseline SUA was associated with attenuated declines in attention (β = 0.006; p = 0.03) and visuospatial abilities (β = 0.007; p = 0.01) in men. There was a trend to suggest higher baseline SUA in men was associated with attenuated declines in language, but this finding did not reach statistical significance (p = 0.09). There were no significant findings with SUA and cognition in women. In this sample of cognitively healthy, community-dwelling adults, we found that higher SUA levels at baseline were associated with attenuated declines in attention and visuospatial abilities in men. SUA was not associated with cognition or change in cognition over time in women.

Application of Ion Chromatography Coupled with Mass Spectrometry for Human Serum and Urine Metabolomics

“…In addition, we compared polar metabolite profiles between male and female subjects. The enriched levels of uric acid and its derivative allantoin in serum from male subjects were consistent with those described in previous works using different metabolomics platforms, 23,39,40 verifying the analytical reliability of our IC-MS metabolomics platform. To date, the mechanisms responsible for the gender-associated differences in uric acid and its derivative remain unclear.…”

Assessment of Serum Uric Acid Levels According to Sex and Stage for Patients with Alzheimer-type Dementia

“…Another study did not identify a significant correlation between serum UA concentrations and cognitive functions in females. In males, high serum UA concentrations were associated with reduced attention and visuospatial functions (46). In our study, we found no differences between the UA concentrations of the female and male participants in the AD and control groups.…”

Uric acid enhances longevity and endurance and protects the brain against ischemia

“…Indeed, BDNF is known to protect neurons against oxidative and metabolic stress and to enhance synaptic plasticity and learning and memory (Greenberg et al, 2009; Mattson et al, 2004). In a longitudinal study of healthy adults, higher serum UA levels were associated with slower decline in visuospatial abilities and attention in men but not in women (Kueider et al, 2017). Previous studies demonstrated positive associations between blood UA levels and high energy/drive, positive affect, and achievement (Fowler, 1973; Lorenzi et al, 2010; Stevens et al, 1975).…”