Research On Cognitive Dysfunction’s Correlation With Circadian Rhythm Of Blood Pressure And The Promoter Methylation Of PER1 And CRY1 In Cerebral Small Vessel Disease

Objectives1.To verify the effects of different types of the circadian rhythm of blood pressure on cognitive function in patients with cerebral small vessel disease(CSVD).2.To investigate the relationship between DNA promoter methylation of clock genes PER1 and CRY1,circadian rhythm of blood pressure and cognitive dysfunction in patients with CSVD.Methods1.A total of 428 CSVD patients hospitalized in the Geriatrics Department of the Lianyungang Hospital Affiliated to Jiangsu University between May 2018 and June 2022 were enrolled in this study.Patients were divided into the cognitive dysfunction group and the control group.Independent sample t test,Mann-Whitney U test,chi-square test and other statistical methods were used to compare clinical data and parameters of ambulate blood pressure monitoring(ABPM)between the two groups.Finally,binary logistic regression analysis was used to evaluate the effects of different types of circadian rhythm of blood pressure on cognitive dysfunction in patients with CSVD.2.We recruited 217 patients with CSVD admitted to the Geriatrics Department of the Lianyungang Hospital Affiliated to Jiangsu University between March 2021 and June 2022.Patients were also divided into the cognitive dysfunction group and the control group.Peripheral venous blood samples of enrolled patients were collected for methylation-specific PCR.Independent sample t test,Mann-Whitney U test,chi-square test and other statistical methods were used to compare clinical data,ABPM parameters and methylation levels between the two groups,so as to explore the relationship between DNA promoter methylation of PER1 and CRY1,circadian rhythm of blood pressure and cognitive dysfunction in patients with CSVD.Results1.A total of 383 patients with CSVD were included in the study,with an average age of73.55±12.44 years,including 171 males(44.6%)and 212 females(55.4%).The subjects were divided into two groups: 224 cases(58.5%)in the cognitive dysfunction group and 159 cases(41.5%)in the control group.(1)Patients in the cognitive dysfunction group were older,had lower blood pressure on admission,and had a greater number of previous cardiovascular and cerebrovascular diseases(P<0.05).(2)More patients in the cognitive dysfunction group had circadian rhythm abnormalities in blood pressure,especially the reverse-dipper type(P<0.001).(3)In the elderly,there was a statistical difference in the circadian rhythm of blood pressure between the cognitive dysfunction group and the control group,but this phenomenon did not exist in the middle-aged.(4)Binary logistic regression analysis showed that after adjusting for confounding factors,the risk of cognitive dysfunction in CSVD patients with non-dipper type(OR=4.052;95%CI,1.782 ~ 9.211;P=0.001)and reverse-dipper type(OR=8.002;95%CI,3.367~19.017;P<0.001)were higher than that of dipper type.2.A total of 101 patients with CSVD were included in the study,with an average age of70.01±13.01 years,including 56 males(55.4%)and 45 females(44.6%).The subjects were divided into two groups: 65 cases(64.4%)in the cognitive dysfunction group and 36 cases(35.6%)in the control group.(1)Patients in the cognitive dysfunction group were older,less educated and more had a history of hypertension(P<0.05).(2)The promoter methylation rates of PER1 and CRY1 in the peripheral blood of CSVD patients with cognitive dysfunction were significantly higher than those in the control group(P<0.001;P=0.041).(3)There was no statistical significance in the promoter methylation rates of PER1 and CRY1 gene between different types of circadian rhythm of blood pressure(P>0.05).(4)The CSVD total load score of the cognitive dysfunction group was higher than that of the control group(P=0.046).(5)Binary logistic regression analysis showed that after adjusting for confounding factors,patients with PER1 gene promoter methylation(OR=16.565;95%CI,4.057 ~ 67.628;P<0.001)and CRY1 gene promoter methylation(OR=6.017;95%CI,1.290~28.069;P=0.022)had a higher risk of cognitive impairment compared to patients without gene promoter methylation.Conclusions1.Abnormal circadian rhythm of blood pressure in patients with CSVD is independently related to cognitive dysfunction.The disturbance of circadian rhythm of blood pressure may affect the cognitive function of patients with CSVD,and the risk of cognitive dysfunction is higher in non-dipper and reverse-dipper types.2.The promoter methylation rates of PER1 and CRY1 in peripheral blood of CSVD patients were associated with cognitive dysfunction.In addition,the cognitive dysfunction associated with CSVD may also be related to the total load of CSVD.