Study On The Effects Of Folic Acid,DHA And Their Combined Intervention On Elderly People With Mild Cognitive Impairment

Objective 1.To observe the effects of folic acid,DHA and their combined intervention on serum amyloid protein(A?)in elderly people with mild cognitive impairment(MCI)by a randomized controlled study.2.To observe the effects of folic acid,DHA and their combined intervention on the expression of APP/A? metabolism pathway related genes in elderly people with MCI.3.To explore the effects of folic acid,DHA and their combination on the cognitive function of MCI patients,and provide scientific basis and treatment plan for further community early intervention on MCI patients.Method The subjects were selected from people over the age of 60 who were examined in Hujiayuan street community health service center of Binhai new area of Tianjin city from March to June 2016.The cognitive level of the people who meeted the inclusion criteria was assessed by general health questionnaire,Mini-Mental state examination(MMSE)and wechsler adult intelligence scale revision China(WAIS-RC).A total of 138 patients with MCI were collected from the patients after excluding from visits,refusing to draw blood and following up.According to gender,age and education level,MCI patients were randomly divided into placebo group,folic acid group,DHA group and folic acid+DHA group.Folic acid group was administrated by folic acid(800?g/d).DHA group was administrated by DHA(800mg/d).folic acid+DHA group was adminstrated by folic acid 800?g/d and DHA 800mg/d.Placebo group was provided the same dose corn starch and corn oil.The patients were followed up for 6 months.Before and after intervention,the WAIS-RC scale was used to evaluate the characteristics of cognitive impairment in MCI patients,the fasting blood was left for detecting related indexes.Serum folic acid was detected by chemiluminescence and serum homocysteine(Hcy)was tested by enzyme cycle method.The plasma docosahexenoicacid(DHA)and eicosapentaenoic acid(EPA)were examined by gas chromatography.Enzyme linked immunosorbent assay was used to detect the content of amyloid precursor protein(APP),beta-site APP cleaving enzyme1(BACE1),?-amyloid protein 42(A?42)and A?40.The expression levels of APP-m RNA,BACE1-m RNA,PS1-m RNA and PS2-m RNA in blood cells were detected by RT-PCR.Variance analysis,chi square test,nonparametric test and repeated measurement analysis of variance were used to analyze the relationship between folic acid,DHA and combined intervention with serum A? level,expression of APP/A? metabolic pathway related gene and cognitive function in elderly MCI patients.This trial has been registered with Trial Number: Chi CTR-IOR-16008351.Results: The differences of abdominal circumference,hip circumference and diabetes in each group were statistically significant(P<0.05).There was no significant difference in the other characteristics(P>0.05).Serum folic acid: after 6 months intervention,compared with the placebo group,serum folic acid level increased in folic acid group and folic acid+DHA group(P<0.05).Serum Hcy: after 6 months intervention,compared with the placebo group,no significant changes in folic acid group and DHA group.The level of serum Hcy of folic acid+DHA were significantly decreased(P<0.05).Plasma DHA: after 6 months intervention,compared with the placebo group,no significant changes in plasma DHA level in folic acid group.The level of plasma DHA increased in folic acid +DHA group and DHA group(P<0.05).Plasma EPA: there was no significant difference in plasma EPA level between the four groups before and after intervention(P>0.05).Serum A?42 and A?40: after 6 months of intervention,serum A?42 level in folic acid and folic acid+DHA groups were lower than that in placebo group(P<0.05).Serum A?40 content in all three adminitation groups were lower than that in placebo group(P<0.05).A?42/40: after 6 months of intervention,there was no significant difference in A?42/40 in all groups(P>0.05).Serum APP and APP-m RNA expression: compared with the placebo group,after 6 months of intervention,the serum level of APP decreased in folic acid and folic acid+DHA group.No significant change in serum APP level in DHA group was founded(P<0.05).The difference of the expression of APP-m RNA in blood cells between the four groups was not statistically significant(P>0.05).Serum BACE1 and BACE1-m RNA expression: compared with the placebo group,after 6 months of intervention,no significant changes in serum BACE1 levels in all three intervention groups were observed(P>0.05).The expression of BACE1-m RNA in blood cells in DHA and folic acid+DHA group were lower than that in placebo group(P<0.05).PS1-m RNA and PS2-m RNA expression: the difference of PS1-m RNA in blood cells between the four groups had no statistical significance(P>0.05).The expression levles of PS2-m RNA in blood cells in DHA and folic acid+DHA group were lower than that in placebo group(P<0.05).The cognitive level: after 6 months intervention,there was no difference showed in WAIS-RC,knowledge score,charting score,short form IQ and MMSE scores in all groups(P>0.05).However,the sorces of arithmetic,digit span,block pattern,picture arrangement were statistically significant differences in all four groups(P<0.05).Further comparisons showed that folic acid group was better than DHA group in digit span.DHA group intervention was better than folic aicd group in knowledge,arithmetic,block diagram and picture arrangement.Folic acid+DHA group was superior to folic acid group in arithmetic,block diagram and picture arrangement score.Conclusion: 1.Folic acid supplement can improve the digital breadth project in cognitive function;DHA supplement can improve the arithmetic,block diagram and picture arrangement in cognitive function.2.Folic acid administration reduces serum A?42 and A?40 by regulating the level of serum APP in APP/A? metabolism pathway;DHA supplementation reduces the level of A?40 in serum by regulating the expression of BACE1-m RNA and PS2-m RNA in APP/A? metabolic pathway.3.The combined intervention of folic acid and DHA can significantly reduce the content of serum Hcy in the elderly MCI.No obvious combination effect of folic acid and DHA on regulating A? pathway and improving the cognition has been showed.