Relationship Between Cognitive Impairment And Genome-wide Methylation In Alzheimer’s Disease

Objective:The aim of this study was to observe the changes of the whole genome methylation level in patients with Alzheimer’s disease,and to explore the relationship between the cognitive level of AD and the whole genome methylation.Methods:Sixty AD patients diagnosed in a hospital in the first clinical medical college Shanxi medical university from June,2015 to Octobe,2018 were selected and diagnosed with NINCDS-ADRDA standard.According to clinical dementia rating scale(CDR),they were divided into mild,moderate and severe AD groups(n=20 in each group).The dividing standard was: CDR = 0.5-1 for mild dementia;CDR = 2 for moderate dementia;Severe dementia,CDR=3,exclusion criteria include patients with severe internal diseases such as heart,lung and brain.In the control group,60 normal elderly people matched in age,sex and educational level were selected.The cognitive level of all subjects was evaluated by Mini Mental State Examination(MMSE)and CDR,DNA was extracted from peripheral blood,DNA methylation level was detected by Whole Genome Methylation Detection Kit(USA),and the whole genome methylation rate was calculated according to the calculation formula.Results:1.There was no significant difference in age,sex,educational years and prevalence rates of hypertension,hyperlipidemia and diabetes between control group and AD patientgroup.(P>0.05).2.Comparison of MMSE score and whole genome methylation rate between AD patients and control group: Compared with control group,the whole genome methylation rate of AD group is lower,and the difference is statistically significant(P < 0.05).Comparing whole genome methylation rates in patients with AD at different degrees,it was found that whole genome methylation reduction was more significant in patients with moderate and severe AD than in patients with mild AD(P <0.05)(P<0.05).The difference of MMSE total score between the control group and AD group was statistically significant(F=59.738,P<0.001),and the difference of MMSE total score between the two groups was statistically significant(P<0.05).3.Correlation analysis between the whole genome methylation rate and MMSE score:there is a positive correlation between the whole genome methylation rate and MMSE score.With the decrease of the whole genome methylation rate,the MMSE total score also decreases(r=0.493,P<0.001).4.Analysis on the ability of predicting AD by whole genome methylation rate :ROC curve analysis showed that the ROC area under the curve of whole genome methylation rate in predicting AD was 0.812.Conclusion:The whole genome methylation rate of AD patients is reduced,and with the decrease of cognitive level,the whole genome methylation rate is also gradually reduced,The whole genome methylation rate also has high sensitivity and specificity in predicting AD,It is suggested that in clinical and research work,the detection of the whole genome methylation level of peripheral blood may have a certain clinical guiding value for the prevention,early diagnosis and treatment of AD.