Case Control Study And Intervention Trial By Folic Acid Plus Vitamin B₁₂ In Mild Cognitive Impairment Based On Inflammatory Factors

Objective1.The aims of the paired case-control study were to investigate the relationship between peripheral inflammatory biomarkers and mild cognitive impairment（MCI）in the elderly,and to explore the peripheral mechanisms of MCI.2.The aim of the randomized controlled trial was to observe the effects of folic acid and vitamin B₁₂ and their combined intervention on serum inflammatory cytokine levels,inflammatory cell levels and cognitive function in MCI subjects,providing scientific evidence and specific plan for further prevention of early MCI patients in community.Methods1.The 101 cases of MCI subjects screened by the baseline survey were included in the case group.In addition,101 healthy elderly patients were selected as the control group by the method of equal ratio matching.All subjects were subjected to fasting blood sampling.The concentrations of interleukin-6（IL-6）,and tumor necrosis factor-α（TNF-α）were determined by immunomagnetic beads adsorption and kits.The numbers of neutrophils,lymphocytes,white blood cells,and platelets were measured using a cell counting kit,and the neutrophil to lymphocyte ratio（NLR）was calculated.The general conditions and blood biochemical indicators of the two groups were compared,and the correlation between the above blood biochemical indicators and MCI was analyzed.The diagnostic ability of possible biomarkers of MCI was also evaluated.2.The MCI subjects were randomly assigned to four groups:placebo group,folic acid group,vitamin B₁₂ group,and folic acid+vitamin B₁₂ combined intervention group,with 60 in each group.The folic acid group was given oral folic acid of 800μg/d,the vitamin B₁₂ group was given oral vitamin B₁₂ of 25μg/d,the folic acid+vitamin B₁₂ combined intervention group was given oral folic acid of 800μg/d and vitamin B₁₂ of 25μg/d,and the placebo group was given oral placebo.The duration of the intervention was 18 months.We compared the inflammatory biochemical markers and the wechsler adult intelligence scale–revision China（WAIS-RC）scores of the elderly among the four groups at baseline and after 18 months.Repeated measures analysis of variance was used to evaluate the effect of intervention on inflammatory biochemical markers and cognitive function.Results1.The body mass index（BMI）of the MCI group was greater than that of the normal control group（P<0.05）.MMSE score,verbal intelligence quotient（VIQ）score,performative intelligence quotient（PIQ）score,and full intelligence quotient（FIQ）score of the MCI group were all lower than those of the normal control group（P<0.05）.Serum IL-6 and TNF-αconcentration,neutrophil count and NLR ratio of the MCI group were greater than those of the normal control group（P<0.05）.Univariate logistic regression analysis showed that high serum IL-6 concentration（OR:1.240,95%CI:1.104-1.393）and high NLR（OR:5.219,95%CI:2.614-10.420）were risk factors for MCI（P<0.05）.ROC analysis suggested that the optimum IL-6 cut-off point for MCI was 8.71pg/mL,with 69.31%sensitivity,71.29%specificity,70.71%positive predictive values（PPV）and 69.9%negative predictive values（NPV）,and the optimum NLR cut-off point for MCI was 2.00,with 78.22%sensitivity,71.29%specificity,73.15%positive predictive values（PPV）and 76.60%negative predictive values（NPV）.2.After 18 months of intervention,the concentration of IL-6 in the folic acid group and the combined intervention group was lower than those in the placebo group（P<0.05）;the concentration of TNF-αin the folic acid group was lower than that in the placebo group（P<0.05）;the NLR levels in the vitamin B₁₂ group and the combined intervention group were lower than those in the placebo group and the folic acid group（P<0.05）;VIQ scores of the folic acid group,the vitamin B₁₂ group and the combined intervention group were higher than those of the placebo group（P<0.05）.PIQ scores of the folic acid group and the combined intervention group were greater than those of the placebo group,and PIQ score of the combined intervention group was greater than that of the vitamin B₁₂ group（P<0.05）.FIQ scores of the folic acid group and the combined intervention group were greater than those of the placebo group and the vitamin B₁₂ group（P<0.05）.Conclusion1.Serum IL-6 concentration,TNF-αconcentration,neutrophil count,and NLR of the MCI were higher than those of the normal control group;high serum IL-6 level and high NLR were risk factors for MCI in the elderly.The optimal screening cutoff value of IL-6 was 8.71pg/mL,and the optimal diagnostic cutoff value of NLR was 2.00,with good sensitivity,specificity and screening value.2.After 18 months of supplementation with folic acid and vitamin B₁₂ in MCI,the levels of serum inflammatory cytokines（IL-6,TNF-α）and NLR were decreased.The effect of folic acid and vitamin B₁₂ combined intervention was significant.The cognitive function of patients with MCI improved,and the effect of folic acid and vitamin B₁₂ combined intervention was prior to other groups.