High Blood Uric Acid Is Associated With Reduced Risks of Mild Cognitive Impairment Among Older Adults in China: A 9-Year Prospective Cohort Study

Abstract

Background: It remains unsolved that whether blood uric acid (UA) is a neuroprotective or neurotoxic agent. This study aimed to evaluate the longitudinal association of blood UA with mild cognitive impairment (MCI) among older adults in China. Methods: A total of 3,103 older adults (aged 65+ years) free of MCI at baseline were included from the Healthy Aging and Biomarkers Cohort Study (HABCS). Blood UA level was determined by the uricase colorimetry assay and analyzed as both continuous and categorical (by quartile) variables. Global cognition was assessed using the Mini-Mental State Examination four times between 2008 and 2017, with a score below 24 being considered as MCI. Cox proportional hazards models were used to examine the associations. Results: During a 9-year follow-up, 486 (15.7%) participants developed MCI. After adjustment for all covariates, higher UA had a dose-response association with a lower risk of MCI (all P _{for trend} < 0.05). Participants in the highest UA quartile group had a reduced risk [hazard ratio (HR), 0.73; 95% (CI): 0.55-0.96] of MCI, compared with those in the lowest quartile group. The associations were still robust even when considering death as a competing risk. Subgroup analyses revealed that these associations were statistically significant in younger older adults (65-79 years) and those without hyperuricemia. Similar significant associations were observed when treating UA as a continuous variable. Conclusions: High blood UA level is associated with reduced risks of MCI among Chinese older adults, highlighting the potential of managing UA in daily life for maintaining late-life cognition.

Keywords: cognitive function; mild cognitive impairment; older adults; prospective cohort study; uric acid.

FIGURE 1

Flowchart of study participant enrollment in this study. MMSE, Mini-Mental State Examination. UA, uric acid.

FIGURE 2

Adjusted dose-response association between blood UA and risk for MCI. UA, uric acid; HR, hazard ratio; MCI, mild cognitive impairment. Blood UA was coded using a restricted cubic spline (RCS) function with three sex-specific knots, which approximately corresponded to the 5th (170.0 μmol/L), 50th (281.6 μmol/L), and 95th (454.3 μmol/L) percentiles of blood UA distribution. The solid red line represents the adjusted hazard ratio for the risk of MCI for any value of UA compared to participants with 170.0 μmol/L (P5) of blood UA level, with light green shaded areas showing 95% confidence intervals derived from restricted cubic spline regressions. The green histograms show the fraction of the population with the different levels of blood UA. The dashed gray line refers to the reference for the association at an HR of 1.0. P for non-linear = 0.080.

FIGURE 3

Associations of UA quartiles with the risk of MCI in age and sex subgroups. HR, hazard ratio; CIs, confidence intervals. The model was adjusted for age (not in age subgroup) and sex (not in sex subgroup), education, drinking, smoking, marital status, regular exercise, body mass index, central obesity, adequate medical service, hypertension, diabetes mellitus, self-reported history of heart disease, and stroke/CVD. Q1 was defined as the reference group. In the age subgroup, participants aged 65–79 years, the cutoff values of UA quartiles were 245.4, 291.6, and 355.4 μmol/L for men, and 195.2, 242.0, and 296.4 μmol/L for women; participants aged 80 years and older, the cutoff values of UA quartiles were 262.0, 315.0, and 377.1 μmol/L for men, and 220.0, 270.7, and 329.8 μmol/L for women. In the sex subgroup, the cutoff values were 252.0, 305.6, and 365.1 μmol/L for men, and 213.9, 265.0, and 320.9 μmol/L for women.