A Randomized,Double-blind,Placebo-controlled Trial Of Idebenone In The Treatment Of Amnestic Mild Cognitive Impairment And Mild Alzheimer’s Disease

Objective:To investigate the effect of idebenone(IDE)on cognitive function in patients with amnestic mild cognitive impairment(aMCI)and mild Alzheimer disease(mAD)through a randomized,double-blind,placebo-controlled trial study The aim is to provide a safe and effective drug for the clinical management of cognitive impairment.Methods:In this study,a randomized,double-blind,placebo-controlled trial design was used to treat patients with aMCI and mAD with the potent antioxidant idebenone(IDE).90 subjects were admitted to the memory clinic of the First Affiliated Hospital of Shandong First Medical University and were treated with the Mini-mental state examination(MMSE),the The subjects were given the Mini-mental state examination(MMSE),the Montreal cognitive assessment scale(MoCA),the Hamilton depression rating scale(HAMD),the Hamilton anxiety scale(HAMA),and the Clinical Dementia Assessment Scale(CDAS).Forty-nine patients with mAD were randomly divided into the IDE group(24 patients)and the control group(25 patients)by SPSS software,and 41 patients with aMCI were randomly divided into the IDE group(21 patients)and the control group(20 patients)by Clinical Dementia Rating(CDR).The control group was given placebo immediately after enrollment,1 tablet each time,3 times daily,while the IDE group was given IDE after enrollment,1 tablet(30mg)each time,3 times daily.Both groups were administered for 48 weeks,and non-literate subjects were assessed on the Alzheimer’s disease assessment scale(ADAS-cog)at entry,12 weeks,24 weeks,36 weeks and 48 weeks after treatment,and all subjects were assessed on the MMSE and MMSE.All subjects were assessed on the MMSE and MoCA scales,and mAD subjects were assessed on the Activities of daily living scale(ADL)scale.Electrocardiogram,routine blood,liver,kidney and urine tests were also performed.Statistical analysis was performed using SPSS 26.0 and differences were considered statistically significant at P< 0.05.Results:A total of 80 subjects completed the trial.20 patients with mAD in the IDE group and22 in the control group.20 patients with aMCI in the IDE group and 18 in the control group.1.General data: There were no statistically significant differences between the two groups in basic data such as age,gender and education level before treatment(P>0.05).The differences in MMSE,MoCA,HAMD and HAMA scores before treatment were not statistically significant(P> 0.05),and all scores were comparable between the two groups at baseline.2.aMoCA scores in the IDE group of patients with MCI were significantly higher at12,24 and 36 weeks post-treatment than before(all P < 0.05);ADAS-Cog scores were significantly lower at 12,24,36 and 48 weeks post-treatment(all P < 0.01).In the control group,MoCA scores were significantly lower at weeks 36 and 48 after treatment than before(all P<0.05);ADAS-Cog scores were significantly higher at weeks 12,24,36 and48 after treatment than before(all P<0.05).MoCA and ADAS-Cog scores were significantly better in the IDE group compared to the control group in patients with aMCI at 24,36 and 48 weeks post-treatment(all P < 0.05 or 0.01).The above data were analysed using generalized estimating equations(GEE): after adjusting for covariates such as age,gender,education and previous history,the results of the GEE with MoCA and ADAS-Cog scores as the outcome incorporating group and time interaction effects,the IDE group of patients with aMCI showed a significant improvement in MoCA and ADAS-cog scores improved significantly better than the control group at 12,24,36 and 48 weeks post-treatment(all p < 0.01).3.Compared to the pre-treatment period,MMSE and MOCA scores were significantly lower and ADAS-Cog and ADL scores were significantly higher in the IDE group at 24,36 and 48 weeks post-treatment(all P < 0.01);MMSE and MOCA scores were significantly lower and ADAS-Cog and ADL scores were significantly higher in the control group at all time points post-treatment(all P < 0.01).<In the IDE group of mAD patients,the ADAS-Cog score was lower than that of the control group at all time points after treatment,but there was no statistical difference(P > 0.05).4.Observations on safety indicators: No adverse effects were observed during the follow-up period of this study,except for 5 subjects who developed mild sleep disturbance after taking IDE.Conclusions:Regular administration of IDE for 48 weeks was effective in improving cognitive function in patients with aMCI.There was no significant improvement in cognitive function in patients with mAD,but there was a potential tendency to slow down their degree of cognitive decline.The safety of the test dose of IDE was good.