The Effect Of Uric Acid On Cerebral Small Vessel Disease And Related Cognitive Impairment

Objective:To investigate the effect of uric acid(UA)on the total burden score of cerebral small vessel disease(CSVD)and cognitive impairment related to CSVD.Methods:A total of 217 inpatients with CSVD between March 2017 and September 2020 were enrolled retrospectively.According to the total burden score of CSVD,all individuals were divided into two groups:mild-to-moderate CSVD group(0-2 scores)and severe CSVD group(3-4scores).The general data,blood biochemistry and MRI imaging data were collected.The cognitive function were assessed by Montreal cognitive assessment(Mo CA)and mini-mental state examination(MMSE),and then considering different level of education,all patients were divided into two groups:cognitive impairment group and non-cognitive impairment group.Statistical methods such as t test,χ~2 test,Mann-Whitney test were used to compare the difference of clinical characteristic between the two groups based on the total burden score of CSVD.Logistic regression analysis were used to analyze the risk factors of CSVD and its cognitive impairment.Pearson or Spearman correlation analysis was used to evaluate the correlation between UA and the total burden score of CSVD and MMSE and Mo CA in patients with CSVD.Results:1.The severe CSVD group contained a larger proportion of male,hypertension,smoker and a higher level of serum UA,Hcy compared with the mild-to-moderate CSVD group(P<0.05).There was a positive association that the level of serum UA increased with the total burden CSVD score ascended(P=0.005);2.The multivariate logistic regression analysis showed that hypertension(OR=2.574,95%CI=1.236～5.360,P=0.012),the elevated level of serum UA(OR=1.005,95%CI=1.001,1.009,P=0.019)and Hcy(OR=1.027,95%CI=1.002～1.053,P=0.037)were all the independent risk factors for the total burden CSVD score.The univariate logistic regression analysis showed a significant association between serum UA and severe white matter hyperintensity(OR=1.004,95%CI=1.000～1.007,P=0.028)but not lacunar infarcts,cerebral microbleeds,enlarged perivascular spaces(all P>0.05);3.The CSVD patients were equally divided into four groups according to the quartile of serum UA.Multivariate regression after control of confounding factors showed that as the level of UA increased,the risk of total CSVD burden increased,and P for trend was statistical significant(P=0.001).Serum UA(for each quartile increase)was an independent risk factor for total CSVD burden in male patients(OR=1.619,95%CI=1.125～2.330,P=0.010),while no statistically positive results were found in women(P=0.070);4.Compared with CSVD patients with non-cognitive impairment,the serum UA of patients with cognitive impairment increased(P<0.001).The Mo CA and MMSE of CSVD patients were significantly negatively correlated with total CSVD burden(r=-0.368,-0.347,all P<0.001),but not correlated with serum UA(P>0.05).The above relationship didn’t have gender differences.Multivariate logistics regression showed that age(OR=1.058,95%CI=1.022～1.095),the total MRI CSVD burden(OR=1.616,95%CI=1.278～2.044),serum UA(OR=1.006,95%CI=1.001～1.010)are independent risk factors for cognitive impairment in patients with CSVD(all P<0.05).Conclusions:1.Serum UA promotes the progression of CSVD and is an independent risk factor for the increase of the total CSVD burden.2.The impact of UA on CSVD may differs by sex,which is significant in male patients but not females.3.CSVD-related cognitive impairment is closely related to CSVD the total CSVD burden score and serum UA level.