P3‐098: Serum uric acid, cerebrospinal fluid marker of Alzheimer's disease and cognition

Abstract

Lower level of serum uric acid has detrimental effect on the risk of dementia and cognitive impairment in the elderly. However, underlying mechanism for the effect of uric acid has not been elucidated. We investigated the association between serum uric acid and cerebrospinal fluid (CSF) level of biomarkers including beta amyloid (Aβ), tau, total tau (t-tau), and phospho-tau (p-tau) using the database of the Alzheimer's Disease Neuroimaging Initiative (ADNI). According to serum uric acid level, subjects were subgrouped into tertiles. Mixed-effect models were used to evaluate the effect of serum uric acid on CSF biomarkers and longitudinal cognitive decline. Compared to the middle uric acid tertile group, the lowest tertile group and the highest tertile group had lower CSF Aβ levels and higher tau and p-tau levels, although statistical significance was reached only in the lower tertile group. Both the lowest tertile and the highest tertile groups had significantly higher CSF t-tau levels compared to the middle tertile group. Serum uric acid showed detrimental effects on longitudinal MMSE decline: in subjects with baseline MCI, the lower tertile group had faster MMSE decline compared to the middle tertile group (beta = -1.13, p = 0.002), while the higher tertile group tended to have (beta = -0.62, p = 0.072); in subjects with baseline dementia, both the lower tertile group (beta = -2.84, p = 0.002) and the higher tertile group (beta = -2.45, p = 0.010) had faster MMSE decline compared to the middle tertile group; but in subjects with baseline normal cognition, the rate of decline was comparable in the lower tertile (beta = 0.16, p = 0.533) and the higher tertile (beta = 0.07, p =0.724) groups compared to the middle tertile group. Our study showed that serum uric acid is associated with CSF biomarkers of AD regardless of baseline diagnosis and also associated with faster cognitive decline in MCI and dementia patients. Both deficient and excessive serum uric acid showed detrimental effects. These findings may provide explanations for the association between serum uric acid and risk of dementia in the elderly.