Study On The Relationship Between Serum Uric Acid And Cognitive Function In Patients With Cerebral Small Vessel Disease And White Matter Lesions

Background:With the development of MRI,more and more patients with cerebral small vessel disease(CSVD)have been diagnosed.At the 2008International Stroke Conference and the European Stroke Conference,“small strokes,big problems”were first proposed which subsequently attracted researchers from all regions of the world to pay attention to CSVD.The CSVD mainly involves small blood vessels with intracranial blood vessel diameters ranging from 40 to 200?m,including small arteries,capillaries and venules.Imaging is mainly characterized by recent small subcortical infarct,lacune of presumed vascular origin,white matter hypertensity of presumed vascular origin,perivascular space,cerebral microbleeds and brain atrophy.The clinical manifestations of CSVD lack specificity which can be manifested as cognitive impairment,depression,gait disorder and dysuria.White matter lesion(WML)is a kind of CSVD.Histopathological manifestations include myelin rarefaction,axonal and oligodendrocyte loss,perivascular space expansion and mild gliosis,which leads to cognitive dysfunction,affective disorder,gait disorder and dysuria slowly.The characteristics of cognitive impairment in CSVD are mainly the significant damage of executive function and processing speed,while the episodic memory function is relatively complete.In the early stage,most patients with cognitive impairment had no obvious clinical symptoms,so there is an urgent need to find reliable molecular markers that can predict the decline in cognitive function in patients with CSVD.Uric acid is the final product of purine nucleotide metabolism and a natural water-soluble antioxidant in the human body and also has an oxidative effect.It has been reported that serum uric acid(SUA)is an important risk factor for cardiovascular and cerebrovascular diseases in the elderly,so early detection of SUA tests can help detect and prevent cardiovascular disease.SUA levels may also affect the vascular system in a variety of ways,so it may be related to the occurrence and development of the CSCD.Part one Study on serum uric acid and cognitive function in patients with cerebral small vessel diseaseObjective:To investigate the association between serum uric acid and cognitive function in patients with cerebral small vessel disease,in order to provide an effective predictor for cognitive impairment in CSVD patients.Methods:A total of 96 inpatients from September 2017 to September2018 in the Department of Neurology,Hebei General Hospital were selected,of which 64 were CSVD patients.According to the results of MoCA score,patients with cerebral small vessel disease were divided into two groups:cognitive impairment group and cognitive normal group.Among them39 were cognitive impairment group(19 males and 20 females,mean age66.69±12.57),25 in the cognitive normal group(12 males 13 females,mean age 68.40±9.59),32 in the control group including 16 males and 16females(mean age 64.56±6.78).The clinical data were collected to assess the associated possible risk factors related to cognitive function.The multivariate Logistic regression analysis of cognitive function was carried out.A Pearson correlation analysis was performed between the serum uric acid level and the MoCA scale sub-item.The uric acid levels were further grouped to study the relationship between uric acid levels and cognitive function.Results:1.The levels of serum uric acid,body mass index,history of hyper-tension and homocysteine were statistically significant(P<0.05).Two comparisons showed that the levels of serum uric acid in cognitive normal group and cognitive impairment group were higher than those in control group(P<0.001).2.Multivariate Logistic regression analysis showed that the increase of serum uric acid level was related to the occurrence of cognitive impairment(OR=1.006,95%CI 1.000~1.012,P<0.05).After adjusting for other risk factors,the difference was still significant,so serum uric acid level may be an independent risk factor for cognitive impairment.3.Pearson correlation analysis showed that serum uric acid level in cognitive impairment group was negatively correlated with MoCA total score,visual spatial perception,executive function and attention(P<0.05).4.There were 29 cases in SUAN group,and 35 cases in HSUA group.Gender,body mass index,history of hypertension,history of diabetes,history of coronary artery disease,history of hyperlipidaemia,history of smoking,history of drinking,TC,LDL,HDL,Glu,Hcy,memory and language were statistically significant(P<0.05).Part two The relationship between serum uric acid and white matter lesionObjective:This study will explore the correlation between SUA and white matter lesion(WML),and the relationship between serum uric acid level and WML severity.Methods:From September 2016 to September 2018,172 inpatients in neurology department of Hebei General Hospital were selected,including 86in WML group and 86 in normal control group.The clinical data of the two groups were collected to evaluate the risk factors associated with WML.The WML was further analyzed by multivariate Logistic regression.Fazekas grading of WML were evaluated to analyze the SUA in different degree of WML.In contrast,Spearman's grade correlation analysis was used to analyze the correlation between SUA and WML.Results:1.There were 86 cases in WML group,including 49 males and 37females,with an average age of(66.85±11.80)years.41 males and 45females(a total of 86 cases)were in the control group,with an average age of(62.55±10.99)years.The levels of age,history of hypertension,smoking,LDL,Hcy and SUA in WML group were significantly higher than those in control group(P<0.05).2.Logistic regression analysis showed that SUA(OR=1.015,95%CI:1.008~1.023,P<0.01),age(OR=1.054,95%CI:1.004~1.106,P<0.05),history of hypertension(OR=5.426,95%CI:1.674~17.593,P<0.01),Hcy(OR=1.152,95%CI;1.021~1.299,P<0.05).Therefore,the increase of SUA level is related to the occurrence of WML,and the difference is still statistically significant after adjusting for other risk factors,so SUA may be an independent risk factor of WML.3.The WML group was graded according to Fazekas scale,and was divided into mild WML subgroup(33 cases),moderate WML subgroup(30cases)and severe WML subgroup(23 cases).The SUA levels in mild white matter lesions were 327.78±71.29?mol/L),moderate white matter lesions were 364.39±77.67?mol/L),and severe white matter lesions were 412.26±98.64?mol/L).Spearman's grade correlation analysis showed that SUA level was positively correlated with WML grade(r_s=0.553,P<0.01).Conclusions:1.The level of SUA is positively correlated with cognitive impairment in CSVD patients.The higher the level of SUA,the more obvious the decrease of visual spatial perception,executive function and attention.Therefore,serum uric acid may be a predictor of cognitive impairment in cerebral small vessel disease.2.The higher the level of SUA,the more prone WML is to occur,and might be an independent risk factor for cognitive impairment.And SUA level is positively correlated with the severity of WML.Therefore,the detection of serum uric acid may help to predict the occurrence of white matter lesions.