| Background:The prevalence of Alzheimer's disease(AD)is increasing gradually,causing a heavy burden on families and society.Currently there is no ideal medications for the treatment of AD.It is of great significance to strengthen the research on the treatment of AD.The pathogenesis of AD is complex,involving multiple targets,links and pathways,on which the traditional Chinese medicine compound has the advantage of comprehensive effect,with good prospects in the field of prevention and control of AD.Objective:1.To observe the clinical efficacy and safety of Chinese medicine compound Jiannao Yizhi Decoction(JNYZD)for treatment of mild to moderate AD.2.To explore the possible mechanism of the therapeutic effect of JNYZF on mild to moderate AD.Methods:This was a randomized,double blind,double simulation,positive control and non inferiority design trial.Sixty patients with amnestic mild cognitive impairment,mild to moderate AD meeting the included criteria were randomly allocated into either JNYZD or donepezil hydrochloride groups.The experimental group(EG)was given 1 bag of JNYZD granule twice daily and 1 tablet of donepezil hydrochloride simulant once daily.The control group(CG)was given 1 tablet of donepezil hydrochloride once daily and 1 bag of of JNYZD simulant twice daily.This study lasted 6 months.Neuropsychological scales,Chinese medicine syndrome evaluation and serum indexes were observed before and after the intervention.Neuropsychological tests include Alzheimer's disease assessment scale-cognitive subscale(ADAS-cog),mini-mental-state examination(MMSE),Montreal cognitive assessment(MoCA),ability of daily living(ADL).Serum indexes involve Acetylcholine(Ach),Beta amyloid protein(A?),Tau Protein(Tau),Delta-like4(DLL4),Jagged1(JAGl),brain-derived neurotrophic factor(BDNF).Safety biochemical indexs were detected before intervention,3 months and 6 months after intervention,containing liver function tests,kidney function tests blood routine examinations,routine urine tests and electrocardiograms.During the test adverse reactions were observed and recorded if any.Results:1 JNYZD' Effects on Cognitive Function with AD1.1 After intervention,ADAS-cog total score of the two groups was significantly reduced respectively compared with that before the intervention,the difference was statistically significant(P<0.01).And no significant between-group difference was detected(P>0.05).1.2 MMSE total score was significantly improved in both groups,with statistically significant differences(P<0.01).There was no statistical between-group difference in MMSE total score(P>0.05).1.3 The MoCA total score of the two groups was improved respectively after the intervention,and there was a statistical change before the intervention(P<0.01).There was no statistical between-group difference inMoCA total score(P>0.05).1.4 The total effective rate of ADAS-cog in EG and CG was 55.56%,45.84%respectively.There was no statistical difference between the two groups(P>0.05).The total effective rate of MMSE in EG and CG was 59.26%,54.17%respectively,There was no statistical difference between the two groups(P>0.05).The total effective rate of MMSE in EG and CG was 59.26%and 62.5%respectively.The between-group difference was not statistically significant(P>0.05).2 JNYZD' Effects on Ability of Daily Living with ADAfter intervention,there was no statistically difference in ADL total score of the two groups respectively compared with that before the intervention(P>0.05).There was no statistical between-group difference in ADL total score(P>0.05).3 JNYZD' Effects on Traditional Chinese Medicine(TCM)Syndromes with ADAfter intervention,the difference was statistically significant in the main TCM symptom score of the two groups respectively compared with that before the intervention(P<0.01).There was no statistical between-group difference in the main symptom score(P>0.05).The total effective rate of the main symptom score in EG and CG was 74.07%and 66.67%respectively,the difference was not statistically significant(P>0.05),and the EG had an advantage over the CG.The total effective rate of all syndrome integrals in EG and CG was 70.37%,54.17%respectively,and between-group difference was not statistically significant(P>0.05).In the matter of single item of TCM syndromes,the scores of "intelligent impairment"and "fatigue" were decreased respectively after intervention in the two groups,the difference was statistically significant(P<0,05).Besides,the scores of "heaviness of limbs" "heavy-headedness" "cold limbs" in EG also showed a statistically significant decline(P>0.05).And no significant between-group difference was detected(P>0.05).4 JNYZD' Effects on the Level of Serological Indexes Related to AD4.1 After intervention the level of Ach in both groups increased than that before intervention,and the difference was statistically significant(P<0.05).Between the groups there was no statistically significant difference(P>0.05).4.2 The level of A? in both groups was lower than that before intervention,and the change was statistically significant(P<0.05).No significant between-group difference was detected(P>0.05).4.3 The level of Tau in EG group was lower than that before,the difference was statistically significant(P<0.05).The level of Tau in CG group was not statistically significant during the intervention(P>0.05).No significant between-group difference was detected(P>0.05).4.4 After intervention,the concentration levels of Notchl and Jaggedl were increased respectively in the two groups,and the DLL4 was reduced,all the differences were statistically significant(P<0.05).No significant between-group difference was detected(P>0.05).4.5 The level of BDNF in the two groups increased after intervention,with statistically significant difference(P<0.05).No significant between-group difference was detected(P>0.05).5 Safety ObservationDuring the intervention,the safety biochemical indexs of the patients were not found with clinical significant change.No adverse reaction occurred during the trail.Conclusion:1.JNYZD has proved effection on AD,it can improve the cognitive function,alleviate clinical symptoms such as intelligent impairment,fatigue,heaviness of limbs,heavy-headedness and cold limbs.2.The mechanism of the therapeutic effect of JNYZD on AD may be related topromoting the production or release of Ach and BDNF,regulating brain neurogenesis and angiogenesis(promoting Notch1,Jagged1,restraining DLL4),and inhibiting A?and Tau.3.The treatment of JNYZD for AD is safety,with no obvious damage to the liver and kidney function or other side effects. |
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