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Please use this identifier to cite or link to this item: http://hdl.handle.net/2262/59506

Title: Donepezil Impairs Memory in Healthy Older Subjects: Behavioural, EEG and Simultaneous EEG/fMRI Biomarkers
Author: BALSTERS, JOSHUA
LAWLOR, BRIAN
O'CONNELL, REDMOND
BRENNAN, SABINA
CASSIDY, SARAH
ROBERTSON, IAN H
BOKDE, ARUN LAWRENCE WARREN
FAGAN, ANDREW JOHN
MEANEY, JAMES
DELMONTE, SONJA
Sponsor: Irish Research Council for Science Engineering and Technology
GlaxoSmithKline
Author's Homepage: http://people.tcd.ie/iroberts
http://people.tcd.ie/balsterj
http://people.tcd.ie/lawlorba
http://people.tcd.ie/reoconne
http://people.tcd.ie/brennas7
http://people.tcd.ie/cassids4
http://people.tcd.ie/bokdea
http://people.tcd.ie/faganan
http://people.tcd.ie/jmeaney
http://people.tcd.ie/delmonts
Keywords: Neuroscience
Alzheimer’s Disease
Issue Date: 2011
Citation: Joshua 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, e24126
Series/Report no.: PLoS ONE
6
9
Abstract: Rising 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.
Description: PUBLISHED
URI: http://hdl.handle.net/2262/59506
Related links: http://dx.doi.org/10.1371/journal.pone.0024126
Appears in Collections:Psychology (Scholarly Publications)

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