Efficacy And Safety Of Cholinesterase Inhibitors In The Treatment Of Severe Alzheimer’s Disease: A Systemic Review And Meta-analysis Of Randomized Controlled Trials

Objective: To evaluate the efficacy and safety of cholinesterase inhibitors(Ch EIs)in the treatment of severe Alzheimer’s disease(AD)by analyzing the evidence provided by randomized controlled trials(RCTs).Methods: The literature published in Pub Med,Embase,and Cochrane Library before February 2021 were searched and screened according to the inclusion criteria that established for the systematic review and meta-analysis.Severe Impairment Battery(SIB),Alzheimer Disease Cooperative Study–Activities of Daily Living–severe version(ADCSADL-SEV),Clinician’s Interview-Based Impression of Change-Plus caregiver input(CIBIC+),and Neuropsychiatric Inventory(NPI)were used as outcomes to evaluate the efficacy in terms of cognition,function,global states,and behavior.Safety was assessed by the incidence of withdrawal due to adverse events,any adverse events,and any withdrawal.Results: 8 RCTs involving 2848 patients with severe AD were included in this study.The meta-analysis of 5 RCTs showed that donepezil had significant differences on SIB(MD:6.07,95% CI: 4.70,7.45;P<0.00001),ADCS-ADL-SEV(MD: 1.04,95% CI: 0.27,1.82;P=0.008),CIBIC+(OR: 1.88,95% CI: 1.46,2.42;P<0.00001)in patients with severe AD compared to placebo,but no significant difference on NPI(MD:-2.13,95% CI:-6.28,2.01;P=0.31).The incidence of withdrawal due to adverse events(OR=1.65,95% CI: 1.15,2.36;P=0.007)and any adverse events(OR=1.58,95% CI: 1.22,2.05;P=0.0005)of donepezil at conventional dose was significantly higher than that of the control group.Conclusion: Overall,our results suggested that Ch EIs had benefits in patients with severe AD on cognition,function,and global states can be used as a medication choice for severe AD.At the same time,we should pay attention to monitoring the occurrence of adverse events.