Cognitive event-related potentials as indicators of donepezil treatment effects in mild Alzheimer s disease

Tieges, Z., Kilborn, K., Price, J., Conway, B.A., Hughes, A. and McLean, G.S. (2010) Cognitive event-related potentials as indicators of donepezil treatment effects in mild Alzheimer s disease. Alzheimer's and Dementia, 6(4), S17. (doi: 10.1016/j.jalz.2010.05.048)

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Background: In previous research we identified ERP and behavioural features associated with memory that produced good discrimination between mild AD and controls. Two prominent markers include a difference wave around 600ms, and memory performance (d' measures). In the current study, we explore whether these markers of brain and cognitive function are sensitive to treatment effects of donepezil. Methods: We examined a range of ERP components and behavioral data based on a crossmodal episodic memory task designed to elicit activity in the hippocampus. The task entails an old/new decision to simple visual images coupled with auditory words. For example, the image of a train is presented with the word “tunnel.” Some pairs are presented a second or third time, at varying intervals. Dense array (128 channel) EEG is acquired continuously during testing. Patients newly diagnosed with probable AD participated in four successive test sessions: pre-treatment Session 1, and post-treatment Session 2 (1 week), Session 3 (4 weeks) and Session 4 (12 weeks). All patients received donepezil. We report here the findings for 8 patients who have completed all test sessions in the ongoing study. Results: We observed significant effects between pre-treatment and post-treatment conditions, as measured by both behaviorial (d') and ERP variables. T-tests with the d' measure show significant differences between Session 1 and 3 (t = -2.45, p < 0.045), and between Session 3 and 4 (t = -2.50, p < .042). These differences indicate an improvement in memory task performance is associated with treatment. We also observed memory-related ERP effects that vary according to treatment condition. In the time interval 520-580ms post-stimulus, in healthy controls we observe a left frontal negativity that is coupled with a right parietal positivity. Pre-treatment, this effect is greatly attenuated in AD patients. However, by Session 4 (12 weeks), we observe apparent recovery of this functional ERP pattern (Memory x Session, F = 3.45, p < 0.009; Session 1 vs Session 4, F = 12.88, p < .013). Conclusions: The improvement in memory performance, together with the recovery of brain function, indicate that cognitive ERP methods are sensitive to treatment affects of donepezil in AD.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Kilborn, Dr Kerry and Tieges, Dr Zoe and Price, Miss Jessica
Authors: Tieges, Z., Kilborn, K., Price, J., Conway, B.A., Hughes, A., and McLean, G.S.
College/School:College of Science and Engineering > School of Psychology
Journal Name:Alzheimer's and Dementia

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