Higher baseline serum uric acid is associated with poorer cognition but not rates of cognitive decline in women

Abstract

Serum uric acid is a powerful antioxidant that may have neuroprotective properties. While some studies have found that greater serum uric acid is associated with better cognition in older adults, it is also associated with numerous vascular risk factors that increase risk for dementia. Women may also be particularly vulnerable to the vascular effects of elevated uric acid. We previously found that mildly elevated serum uric acid is a biomarker of cognitive dysfunction in older adults, and that this likely is mediated by cerebral ischemic burden. Here we examine both cross-sectional and longitudinal associations between serum uric acid, and declines in cognition and functioning in 423 cognitively healthy community-dwelling older women in the Women’s Health and Aging Study (WHAS II). We hypothesized that higher serum uric acid would be associated with poorer concurrent functioning and greater declines over 9 years. In linear regression analyses, higher baseline serum uric acid was associated with poorer working memory, with a trend towards slower manual speed and dexterity before and after adjusting for baseline serum uric acid, demographic and health/cardiovascular variables. However, there were no associations for global cognitive functioning, learning/memory, sequencing, verbal fluency, or visuoconstruction. Mixed effects models also revealed no association with subsequent cognitive declines. Future research should examine changes in serum uric acid at earlier periods in the lifespan and their relationships with later cognitive declines.

Serum Uric Acid and Its Association with Longitudinal Cognitive Change Among Urban Adults

“…[5–13] Most recently, a cohort study of 423 cognitively healthy community-dwelling older women participating in the Women’s Health and Aging Study (WHAS II) observed that a higher SUA base was associated with poorer working memory, with a trend toward slower manual speed and dexterity, after adjusting for several potential demographic and health confounders. [5] This pattern of association was replicated when a study showed that higher SUA base correlated with greater white matter atrophy [13] and cerebral ischemic burden using volume of hyperintense signal on T2-weighted brain MRI scans as a marker among older adults. [12] The latter studies indicated that the relationship between higher SUA and cognitive dysfunction may be mediated by white matter atrophy and cerebral ischemia.…”

“…[7, 12, 13, 19] As stated earlier, recent evidence suggests that SUA may have a beneficial or no significant cognitive effect among men, while having a potential deleterious effect among women, particularly older women. [5, 20–24] The deleterious effect observed between SUA at baseline and decline in visual memory overall, may be driven by brain infarction occurring mainly among women in specific regions of the brain related to visual memory. [23] Despite the lack of effect modification by sex or by sex and age group, this association was in fact restricted to women (p<0.05 for older women, p<0.01 for younger women).…”

“…Our choice of age and sex as stratifying variables were guided by the previous literature which has shown that the effect of uric acid on cognitive decline was mostly seen in older women. [5] Variable time of follow-up is accounted for in the mixed-effects regression model as annual rate of change in the outcome was of primary interest.…”

“…Previous studies have examined the association between SUA with various cognitive outcomes among middle-aged and older adults[4–19] Some, report a potentially adverse effect of hyperuricemia on cognitive outcomes over-time,[5–13] while others suggest a beneficial effect on cognitive performance or slower rate of cognitive decline. [14–19] Prior study limitations included exposure measurement error,[14] selection bias,[14] small sample sizes (<200 subjects) and/or lack of generalizability.…”

“…[5] First, SUA is more strongly associated with cardiovascular disease incidence and all-cause mortality among women than men, particularly among postmenopausal women [20–22]. Secondly, a study by Heo et al[23] uncovered a dose-response relationship between SUA and brain infarction only among women.…”