Effect And Mechanism Of Folic Acid And Docosahexaenoic Acid On Improving Cognitive Function Of Elderly With Mild Cognitive Impairment Via Telomere

ObjectiveMild cognitive impairment(MCI)is the early status of Alzheimer’s disease,(AD).Delaying the decline of cognitive function in the elderly with MCI is an important means to prevent AD.The objective of this study was to discuss the mediating effect of telomere in the relationship between folic acid(FA)or docosahexaenoic acid(DHA)and cognitive function,whether the combined intervention of FA and DHA has a synergistic effect on the improvement of cognitive function in the elderly with MCI,and whether they can ameliorate the cognitive function of the elderly with MCI by delaying telomere shorting.MethodIn the case-control study,280 MCI elderly and 280 cognitively normal elderly were matched according to the same sex,two years in age and one year in education.The cognitive function was estimated by the scores of mini mental state examination(MMSE).Serum folate,Hcy,plasma DHA,leukocytes telomere length(LTL)and mitochondrial copy number were detected.The relationships between folate,Hcy,DHA,LTL,mitochondrial copy number and cognitive function were analyzed by Pearson correlation analysis and logistic regression.Structural equation models were used to analyze the mediating effect of LTL in the relationship between FA or DHA and cognitive function.In the randomized double-blind controlled trial,280 elderly patients with MCI were randomly divided into FA+DHA group(800 μg FA + 800 mg DHA/d),FA group(800 μg FA/d),DHA group(800 mg DHA/d)and Placebo group,with 70 subjects in each group.Cognitive function,peripheral folate,Hcy,DHA,LTL,telomere related protein mRNA expression,oxidative stress levels,mitochondrial function,p53 protein levels and p53-mRNA expression were measured at baseline and 12 months.Mixed linear models were used to analyze the changes of the above indexes after 12 months of intervention.ResultThe results of case-control study showed that,the serum folate and plasma DHA levels,LTL and mitochondrial copy numbers of MCI group were lower and the serum Hcy levels of MCI group was higher(P < 0.05),comparing with control group.The levels of folate,DHA,LTLs and numbers of mitochondrial copy number were positively correlated with MMSE scores,while the levels of Hcy was negatively correlated with LTL(P<0.05).Higher levels of folate,DHA,LTL and mitochondrial copy number were the protective factors of MCI,while higher levels of Hcy was a risk factor of MCI.The levels of folate,LTL and Hcy were negatively correlated,and the levels of LTL and DHA were positively correlated(P<0.05).LTL played mediating roles in the relationship of Hcy and cognitive function,and DHA and cognitive function(P<0.05),and the mediating effects were 21.90% and 12.10%.Hcy levels and LTL played a tandem mediating role in the relationship between folate levels and MMSE scores(P<0.05).The results of randomized double-blind controlled trial showed that,after a 12 months intervention,the full scale IQ(FIQ),verbal IQ(VIQ),performance IQ(PIQ),information,arithmetic,similar and block diagram scores in FA + DHA group,the FIQ,VIQ,information,arithmetic and similar scores in FA group and DHA group,were higher,comparing with placebo group(P<0.05).The FIQ,PIQ and block diagram scores in FA+DHA group were higher,comparing with FA group or DHA group(P<0.05).The LTL in FA + DHA group,FA group and DHA group were longer;the expression of TRF2-mRNA in FA + DHA group,FA group and DHA group were lower;the levels of hydrogen peroxide in FA+DHA group were lower;the ability of inhibiting superoxide anion in FA+DHA group and FA group were higher;the content of genomic 8-oxo G in FA+DHA group,FA group and DHA group were lower;the mitochondrial copy number in FA+DHA group,FA group and DHA group were higher;the mitochondrial deletion in FA+DHA group and FA group were less;the levels of p53 in FA+DHA group,FA group and DHA group were lower,comparing with placebo group(P < 0.05).ConclusionThe levels of folate,DHA,Hcy and LTL were related to cognitive function of the elderly.Folic acid,DHA can improve the cognitive function of MCI elderly.The effect of folic acid and DHA combined intervention is better than that of folic acid and DHA alone.Folic acid and DHA may play a synergistic role in improving the cognitive function of MCI elderly.Folic acid and DHA may improve cognitive function of MCI elderly by delaying telomere shortening.