Donepezil Impairs Memory in Healthy Older Subjects Behavioural, EEG and Simultaneous EEGfMRI Biomarkers 英文参考文献.docVIP

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Donepezil Impairs Memory in Healthy Older Subjects Behavioural, EEG and Simultaneous EEGfMRI Biomarkers 英文参考文献.doc

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Donepezil Impairs Memory in Healthy Older Subjects Behavioural, EEG and Simultaneous EEGfMRI Biomarkers 英文参考文献

DonepezilImpairsMemoryinHealthyOlderSubjects: Behavioural,EEGandSimultaneousEEG/fMRIBiomarkers JoshuaH.Balsters1*,RedmondG.O’Connell1,MaryP.Martin3,AlessandraGalli1,SarahM.Cassidy1, SophiaM.Kilcullen1,SonjaDelmonte1,SabinaBrennan1,JimF.Meaney4,AndrewJ.Fagan4,ArunL.W. Bokde2,NeilUpton5,RobertLai5,6,MarcLaruelle5,BrianLawlor3,IanH.Robertson1 1Trinity CollegeInstitute ofNeuroscience andSchool ofPsychology, Trinity College Dublin, Dublin, Ireland, 2Trinity College Institute ofNeuroscience andSchool of Medicine,TrinityCollegeDublin,Dublin,Ireland,3Mercer’sInstituteforResearchonAgeing,St.James’sHospital,Dublin,Ireland,4CentreforAdvancedMedicalImaging (CAMI),St.James’sHospital,TrinityCollegeDublin,Dublin,Ireland,5NeurosciencesCentreofExcellenceforDrugDiscovery,GlaxoSmithKline,Harlow,UnitedKingdom, 6NeurosciencesDiscoveryMedicine,GlaxoSmithKline,Harlow,UnitedKingdom Abstract Risinglifeexpectanciescoupledwithanincreasingawarenessofage-relatedcognitivedeclinehaveledtotheunwarranted useofpsychopharmaceuticals, includingacetylcholinesterase inhibitors(AChEIs), bysignificantnumbers ofhealthyolder individuals.Thistrendhasdevelopeddespiteverylimiteddataregardingtheeffectivenessofsuchdrugsonnon-clinical groupsandrecentworkindicatesthatAChEIscanhavenegativecognitiveeffectsinhealthypopulations.Forthefirsttime, we use a combination of EEG and simultaneous EEG/fMRI to examine the effects of a commonly prescribed AChEI (donepezil)oncognitioninhealthyolderparticipants.Theshort-andlong-termimpactofdonepezilwasassessedusingtwo double-blind, placebo-controlled trials. In both cases, we utilised cognitive (paired associates learning (CPAL)) and electrophysiologicalmeasures(restingEEGpower)thathavedemonstratedhigh-sensitivitytoage-relatedcognitivedecline. Experiment1testedtheeffectsof5mg/perdaydosageoncognitiveandEEGmarkersat6-hour,2-weekand4-weekfollow- ups. In experiment 2, the same markers were further scrutinised using simultaneous EEG/fMRI after a single 5mg dose. Experiment1foundsi