Show simple item record

dc.contributor.authorFAGAN, ANDREWen
dc.contributor.authorROBERTSON, IANen
dc.contributor.authorBALSTERS, JOSHUAen
dc.contributor.authorO'CONNELL, REDMONDen
dc.contributor.authorCASSIDY, SARAHen
dc.contributor.authorKILCULLEN, SOPHIAen
dc.contributor.authorDELMONTE, SONJAen
dc.contributor.authorBRENNAN, SABINAen
dc.contributor.authorMEANEY, JAMESen
dc.contributor.authorBOKDE, ARUNen
dc.contributor.authorLAWLOR, BRIANen
dc.contributor.authorBRENNAN, SABINAen
dc.date.accessioned2011-09-16T15:21:49Z
dc.date.available2011-09-16T15:21:49Z
dc.date.issued2011en
dc.date.submitted2011en
dc.identifier.citationJoshua H. Balsters, Redmond G. O'Connell, Mary P. Martin, Alessandra Galli, Sarah M. Cassidy, Sophia M. Kilcullen, Sonja Delmonte, Sabina Brennan, Jim F. Meaney, Andrew J. Fagan, Arun L. W. Bokde, Neil Upton, Robert Lai, Marc Laruelle, Brian Lawlor, Ian H. Robertson, Donepezil Impairs Memory in Healthy Older Subjects: Behavioural, EEG and Simultaneous EEG/fMRI Biomarkers, PLoS ONE, 6, 9, 2011, e24126en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/59506
dc.descriptionPUBLISHEDen
dc.description.abstractRising life expectancies coupled with an increasing awareness of age-related cognitive decline have led to the unwarranted use of psychopharmaceuticals, including acetylcholinesterase inhibitors (AChEIs), by significant numbers of healthy older individuals. This trend has developed despite very limited data regarding the effectiveness of such drugs on non-clinical groups and recent work indicates that AChEIs can have negative cognitive effects in healthy populations. For the first time, we use a combination of EEG and simultaneous EEG/fMRI to examine the effects of a commonly prescribed AChEI (donepezil) on cognition in healthy older participants. The short- and long-term impact of donepezil was assessed using two double-blind, placebo-controlled trials. In both cases, we utilised cognitive (paired associates learning (CPAL)) and electrophysiological measures (resting EEG power) that have demonstrated high-sensitivity to age-related cognitive decline. Experiment 1 tested the effects of 5 mg/per day dosage on cognitive and EEG markers at 6-hour, 2-week and 4-week follow-ups. In experiment 2, the same markers were further scrutinised using simultaneous EEG/fMRI after a single 5 mg dose. Experiment 1 found significant negative effects of donepezil on CPAL and resting Alpha and Beta band power. Experiment 2 replicated these results and found additional drug-related increases in the Delta band. EEG/fMRI analyses revealed that these oscillatory differences were associated with activity differences in the left hippocampus (Delta), right frontal-parietal network (Alpha), and default-mode network (Beta). We demonstrate the utility of simple cognitive and EEG measures in evaluating drug responses after acute and chronic donepezil administration. The presentation of previously established markers of age-related cognitive decline indicates that AChEIs can impair cognitive function in healthy older individuals. To our knowledge this is the first study to identify the precise neuroanatomical origins of EEG drug markers using simultaneous EEG/fMRI. The results of this study may be useful for evaluating novel drugs for cognitive enhancement.en
dc.description.sponsorshipJ.H.B., R.O., M.M., S.M.C., S.M.K., S.D., S.B., B.L., and I.H.R. received funding from the GlaxoSmithKline/Trinity College Institute of Neuroscience Research Consortium on Neurodegeneration. J.H.B and R.O. are additionally supported by fellowships from the Irish Research Council for Science Engineering and Technology (IRCSET). N.U., R.L. and M.L. are employees of GlaxoSmithKline and assisted in study design and the preparation of this manuscript. A.G. was supported by funding from Technology Research for Independent Living (TRIL). The funders had no role in data collection, analysis or the decision to publish.en
dc.format.extente24126en
dc.language.isoenen
dc.relation.ispartofseriesPLoS ONEen
dc.relation.ispartofseries6en
dc.relation.ispartofseries9en
dc.rightsYen
dc.subjectNeuroscienceen
dc.subjectAlzheimer?s Diseaseen
dc.titleDonepezil Impairs Memory in Healthy Older Subjects: Behavioural, EEG and Simultaneous EEG/fMRI Biomarkersen
dc.typeJournal Articleen
dc.contributor.sponsorIrish Research Council for Science and Engineering Technology (IRCSET)en
dc.contributor.sponsorGlaxoSmithKlineen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/irobertsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/jmeaneyen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/reoconneen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/fagananen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/lawlorbaen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/brennas7en
dc.identifier.peoplefinderurlhttp://people.tcd.ie/balsterjen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/bokdeaen
dc.identifier.rssinternalid74986en
dc.subject.TCDThemeAgeingen
dc.subject.TCDThemeNeuroscienceen
dc.identifier.rssurihttp://dx.doi.org/10.1371/journal.pone.0024126en


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record