Effects And Mechanisms Of Vitamin D₃ On Elderly People With Mild Cognitive Impairment In The Community

Objective1.Evaluate whether vitamin D₃ supplementation could improve cognitive function among elderly MCI populations and influence the expression of AD related genes;2.Further explore whether vitamin D₃ affects inflammatory factors and blood lipids to achieve the purpose of improving cognition and its underlying mechanisms.MethodsThis study was a randomized,double-blind,placebo-controlled trial.A total of181 elderly MCI（aged 65 years and older）were randomly assigned to either group A or group B.From the unblinding results we could see that group A including 93subjects who took 1 capsule A containing 400 IU of vitamin D₃ daily was vitamin D₃group（hereinafter referred to as VD group）;Group B including 88 subjects who took1 capsule B containing starch granules daily was placebo group.Repeated measures of cognitive function,AD-related gene expression,inflammatory factor levels,and lipid concentrations were conducted at 0,6,and 12 months.Statistical analysis was performed using SAS 9.3 software.Two-sample t-test or chi-square test was used to compare differences between groups.The generalized estimating equation（GEE）was used to measure changes in cognitive function,AD-related gene expression,inflammatory factor levels,and lipid concentrations between different interventions over the past 12 months.This study is in line with the principles of the Helsinki Declaration and approved by the Ethics Committee of Tianjin Medical University,China.All participants expressed their willingness to participate in and sign the informed consent form prior to the intervention.The trial has been registered online and approved at the China Clinical Registry（No.:ChiCTR-IOR-16009307http://www.chictr.org.cn/showproj.aspx?proj=15255）.Results1.It was estimated that the sample size would be 181.But during the period of trial,a total of 18 people withdrew.Finally 163 cases of data met the criteria,among whom 80 patients were in the VD group and while 83 in the placebo group.There was no significant difference in the withdrawal rate between the two groups（VD group:14.0%;placebo group:5.7%;?²=3.48,P=0.060）.Baseline results showed no statistically significant differences in general demographic data,lifestyle,disease history,concentration of vitamin D₃ and cognition between the two groups.2.During the follow-up period full IQ,performance IQ,verbal IQ,and five subscales of the wechsler adult intelligence scale-Chinese revised（WAIS-RC）changed more in the VD group than in the placebo group（P<.001）.After adjusting for the model,concentration changes in presenilin1-mRNA（presenilin1-mRNA）,amyloid precursor protein-mRNA（APP mRNA）andβ-site APP cleaving enzyme-mRNA（BACE1-mRNA）were statistically different between the two groups,and the concentrations of latter two were decreased more in VD group than in placebo.3.Over the past 12 months,the concentration changes of inflammatory factors amyloidβprotein 40(Aβ₄₀),amyloidβprotein 42(Aβ₄₂),interleukin-6（IL-6）and tumor necrosis factor-α（TNF-α）showed statistical differences between the VD and placebo groups（P<.001）.Aβ₄₂ decreased in both groups,and the degree in the VD group（-12.59%）was more pronounced.IL-6 and TNF-αdecreased in the VD group and increased in the placebo group.Further analysis found that Aβ₄₂（estimated value P=0.012,β=-0.03）and IL-6（P=0.002,estimated valueβ=-0.29）were negatively correlated with full IQ.4.During the intervention period,the concentration changes of total cholesterol（TC）,triglyceride（TG）,high-density lipoprotein cholesterol（HDL-C）and low-density lipoprotein cholesterol（LDL-C）were different between two groups（P<.001）.And these four indexes decreased in the VD group（P<.001）.While blood25-hydroxyvitamin D₃（25-OH-VitD₃）,1,25-dihydroxyvitamin D₃（1,25-（OH）₂-VitD₃）increased（P<.001）.GEE also showed a negative correlation between baseline blood TC concentration（P=0.023,estimated valueβ=-0.40）and full IQ.Conclusion1.Daily taking 400IU vitamin D₃ supplement for 12 months can significantly improve cognitive function in elderly MCI patients.In addition,vitamin D₃supplement also reduced the expression of target genes.The latter plays a role in reducing the production and aggregation of Aβ.2.Vitamin D₃ in MCI patients may improve cognition by altering inflammatory factor and lipid levels.