Effects Of Vitamin D₃ Supplementation On Cognitive Function And Blood Biomarkers In Patients With Alzheimer’s Disease

Objective1、Evaluate the effect of vitamin D₃800IU/day for 12 months on the cognitive function of patients with Alzheimer’s disease（AD）;2、To explore the effects of vitamin D₃ supplementation on the levels of inflammatory cytokines,blood lipids and AD-related genes in AD patients,and the correlation between baseline levels and cognitive performance.MethodsThis study was a double-blind,randomized,placebo-controlled trial.The random number table was used to divide 210 eligible patients into an intervention group and a control group,with 105 people in each group.The intervention group took vitamin D800IU/day（2 capsules/day,12 months）,and the control group took the starch granules（2 capsules/day,12 months）with the same appearance as the intervention drug.Cognitive function,inflammatory factor,blood lipid and AD-related genes expression were measured in the two groups at baseline,6months and 12months.The t test or?² test was used to compare the baseline characteristics of the two groups.And generalized estimating equation was used to evaluate the effect of vitamin D₃intervention on cognitive function and blood related biomarkers over 12 months,and to explore the correlation between baseline biomarkers and cognitive function.This research complies with the"Ethical Review Methods for Biomedical Research Involving Humans（Trial）"and the relevant provisions of the Helsinki Declaration on Biological Human Testing,and was approved by the Ethics Committee of Tianjin Medical University.All subjects volunteered to participate in the trial and signed informed consent.Clinical trial registration number:Chi CTR-IIR-16009549.Results1、Among the eligible 210 patients,one patient in the control group withdrew,resulting in 209 patients who completed the study at last（intervention group:n=105;control group:n=104）.There were no statistically significant differences between the two group in sociodemographic characteristics,family history,BMI,lifestyle,vitamin D₃ levels,and cognitive function.2、After 12 months of vitamin D₃supplementation,the changes of total IQ,operational IQ,verbal IQ,information,arithmetic,digit span,vocabulary,block design,and picture arrangement scores of the intervention group and control group were significant differences（P<0.01）,and the intervention group scored higher.3、In the two groups,the changes of amyloidβ42(Aβ₄₂),tumor necrosis factor-α（TNF-α）,interleukin-6（IL-6）and Aβ₄₀/Aβ₄₂ levels were significant differences,and Aβ₄₂、TNF-α、IL-6 levels in the intervention group decreased more（P<0.001）,Aβ₄₀/Aβ₄₂ level increased more（P=0.011）.4、Over the 12 months,the high density lipoprotein cholesterol,low density lipoprotein cholesterol,triglyceride,and total cholesterol showed an interaction effect of time and group（P<0.001）,and the intervention group had lower level.In addition,GEE showed that there is a positive correlation between baseline TG and cognition.The higher the baseline triglyceride concentration,the higher cognitive score of operational IQ in AD patients（β=1.427,P=0.026）.5、During the follow up,the amyloid precursor protein（APP）,β-site APP cleaving enzyme（BACE1）,APP m RNA and BACE1 m RNA showed an interaction effect of time and group（P<0.001）,and the intervention group had lower level.In addition,GEE showed that there was an inverse correlation between baseline APP m RNA（P<0.05）,BACE1 m RNA（P=0.005）and cognitive function.The higher baseline concentration,the lower score of IQ in AD patients.Conclusion1、Daily oral vitamin D₃ 800IU for 12 months may improve cognitive function in AD patients.Vitamin D₃ supplementation has certain beneficial effects on the maintenance of cognitive function in AD patients.2、Vitamin D₃ supplementation in elderly AD patients can improve cognitive function and significantly reduce the levels of inflammatory cytokines,blood lipid concentrations and AD-related genes.Therefore,vitamin D₃ may delay the cognitive decline in AD patients by regulating these biomarkers.