| Research background and purpose:Mild Cognitive Impairment(MCI)refers to a transition state in cognitive function between normal aging and Alzheimer’s disease,involving one or more cognitive domains,but without significant impact on daily life or social activities.Research shows that the prevalence of MCI among community residents aged over 50 years globally reaches 15.56%(95% CI: 13.24-18.03%),and is influenced by age,gender,educational level,and region.The prevalence of MCI in the elderly population in China has reached 19%(95% CI: 17-21%).Studies have shown that the annual conversion rate from MCI to Alzheimer’s disease(AD)is about 10%-15%,and after 6 years of follow-up,about 80% of MCI will convert to AD.With the intensification of the global population aging,the prevalence of AD is increasing year by year.Currently,there is no recognized treatment drug for AD,and the early detection,diagnosis,and treatment of AD have become increasingly important.AD is a public health and safety challenge facing all mankind,causing a serious economic burden to families and society.Currently,there is no gold standard for the treatment of MCI,and the intervention methods are mainly cognitive training,sports intervention,intellectual or psychiatric drugs,and the results of treatment effects are not the same.In addition to impairment of cognitive function,patients with MCI may also experience discomfort such as sleep and gastrointestinal symptoms.Probiotics are active bacteria that colonize the intestine and have the ability to regulate the intestinal flora.According to research reports,probiotics such as Lactobacillus and Bifidobacterium have the potential to treat AD.We speculate that supplementing probiotics may be an effective way to treat MCI.Currently,most research on the treatment of MCI has focused on animal research.Whether probiotics can significantly improve the cognitive function of MCI,and whether they can improve the sleep disorders and gastrointestinal symptoms that may be associated with MCI,the possible mechanism of action is not clear.Therefore,we designed a randomized controlled study of probiotic intervention in older adults with MCI.The purpose of this study is to explore the therapeutic effect and safety of probiotics supplementation on patients with MCI,improve the quality of life of patients with MCI,and reduce the possibility of their conversion to AD.If the expected clinical effect can be achieved,it can provide theoretical and practical basis for the clinical nutritional intervention of MCI and the early prevention and treatment of AD.Subjects and Methods:The subjects recruited for this study were 42 MCI patients who were treated in the Eighth People’s Hospital of Chengdu from January 2022 to December 2022,and were randomly divided into probiotics group(n=21)and placebo group(n=21).The probiotics group patients took 2g of probiotics freeze-dried powder(mixed probiotics supplement containing various probiotics such as Lactobacillus plantarum Bio F-228,Lactobacillus lactis Bio F-224,Bifidobacterium lactis CP-9,Lactobacillus rhamnosus bv-77)every day,The patients in the control group continued to be treated according to the routine treatment and nursing plan of the department every day,and the patients in both groups continued to intervene for 12 weeks.Through consulting the case system,interviews were conducted with patients and their families,doctors in charge,and nursing workers to collect general basic data of patients,including medical history,past history,family history,etc.The changes of cognitive function of patients before and after intervention were evaluated with the mini-mental state examination(MMSE)and the Montreal Cognitive Assessment(Mo CA);Pittsburgh sleep quality index(PSQI)was used to evaluate the changes of sleep quality of patients before and after intervention;Gastrointestinal Symptom Rating Scale(GSRS)was used to evaluate the changes of gastrointestinal symptoms before and after intervention;V3-v4 16 Sr RNA sequencing technology was used to analyze the changes of intestinal flora before and after intervention,and enzyme-linked immunosorbent assay was used to determine the serum brain-derived neurotrophic factor(BDNF)before and after intervention.Results:1.Effect of probiotics on cognitive function of patients with MCI.In this study,the subjects were randomly divided into probiotics group and control group.There was no significant difference between the two groups in terms of gender,age,weight,BMI,concurrent chronic disease,AD family history,educational background,etc.There was no significant difference in scores of MMSE scale,Mo CA scale,ADL scale,PSQI scale and GSRS scale.The MMSE score of probiotics group patients was(21.75 ± 2.75)when they were enrolled,and the MMSE score of control group patients was(20.85 ± 2.25)when they were enrolled.After 12 weeks of intervention,the MMSE score of patients in probiotics group(24.75 ± 2.47)and control group(20.95 ± 1.36)were significantly higher than those in control group(P<0.001).The score of Mo CA scale of probiotics group patients was(19.80 ± 1.85),while the score of Mo CA scale of control group patients was(19.80 ± 1.15).After 12 weeks of intervention,the score of Mo CA scale of patients in probiotics group(22.05 ± 2.14)and control group(20.10 ± 1.45)were significantly higher than those in control group(P<0.01).2.Effect of probiotics on sleep of patients with MCI.This study used the PSQI scale to evaluate the sleep status of the two groups of patients before and after the intervention.The PSQI scale score of probiotics group patients was(7.90 ± 2.99)at the time of enrollment,and the PSQI scale score of control group patients was(8.10 ± 1.71)at the time of enrollment.After 12 weeks of intervention,patients in probiotics group scored(5.35 ± 2.78)on the PSQI scale,while patients in control group scored(8.40 ± 1.76)on the PSQI scale.Compared with the PSQI scale score of the control group,the PSQI scale score of the probiotics group decreased significantly(P<0.001).3.Effect of probiotics on gastrointestinal symptoms of patients with MCI.This study used the GSRS scale to evaluate the gastrointestinal function of the two groups of patients before and after the intervention.The GSRS scale score of probiotics group patients was(28.35 ± 4.17)when they were enrolled,and the GSRS scale score of control group patients was(30.90 ± 4.06)when they were enrolled.After 12 weeks of intervention,the GSRS score of patients in probiotics group(24.80 ± 2.90)and control group(30.35 ±3.53)were significantly lower than those in control group(P<0.001).4.Effect of probiotics on serum BDNF level in patients with MCI.This study evaluated the serum BDNF of two groups of patients before and after intervention.The serum BDNF level of patients in probiotics group was 19.56 ± 1.66ng/ml at the time of enrollment,and that of patients in control group was 19.04 ± 1.12ng/ml at the time of enrollment.After 12 weeks of intervention,the serum BDNF level of patients in probiotics group was 20.06 ± 1.19ng/ml,and the serum BDNF level of patients in control group was 19.10 ± 1.19ng/ml.Compared with the serum BDNF level of patients in the control group,the serum BDNF level of patients in the probiotics group increased significantly after intervention(P<0.05).5.Probiotics affect the abundance of intestinal flora in elderly people with MCI.The study used 16 S r RNA technology to evaluate the changes of intestinal flora in the two groups of patients before and after intervention.At the beginning of the study,there was no significant difference in the abundance of intestinal flora between patients in the probiotic group and those in the control group at different developmental levels(phyla,class,order,family,genus)alpha Diversity and beta There was also no significant difference in diversity.After 12 weeks of intervention,the abundance of Bacteroides in the probiotic group was significantly higher than that in the control group at the phylum level(P<0.05);At the class level,the abundance of Bacteroides in the probiotic group was significantly higher than that in the control group(P<0.05);At the order level,the abundance of Bacteroides in the probiotic group was significantly higher than that in the control group(P<0.05);At the family level,there was no significant change in the relative abundance of bacterial flora in the probiotic group compared to the control group(P>0.05);At the genus level,compared with the control group,patients in the probiotics group had a significant increase in Blautia,Lachnospiraceae,Muribaceae,Anaerostipes,Coprococcus,Ruminococcus,and Prevotellaceae(P<0.05);Compared with the control group,the abundance of Escherichia-Shigella in the probiotic group decreased significantly(P<0.05).After intervention,No statistical differences were found in alpha diversity of intestinal flora among probiotic supplement group and the control group(P>0.05);The differences in beta diversity of intestinal flora among probiotic group and the control group were statistically significant(P<0.05).Conclusions:(1)Probiotic intervention improved cognitive function in older adults with MCI,with significant improvement in memory and attention.(2)Probiotic interventions improved sleep and gastrointestinal symptoms in older adults with MCI.(3)Probiotic interventions have regulated the abundance of intestinal flora in older adults with MCI,especially increasing the relative abundance of bacteroides at the phylum,class,and order levels,as well as the relative abundance of anaerobic bacteria at the genus level.Changes in intestinal flora abundance may be a potential mechanism for the improvement of symptoms in elderly patients with MCI.(4)Probiotic intervention has improved serum BDNF levels in older adults with MCI,and the improvement of serum BDNF levels may be one of the reasons for the improvement of cognitive function in elderly patients with MCI.(5)The intervention effect of probiotics on older adults with MCI can provide theoretical and practical basis for clinical nutritional intervention in MCI,and also provide a new perspective for the prevention and treatment of cognitive impairment. |
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