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Effects of repetitive paired associative stimulation on brain plasticity and working memory in Alzheimer’s disease: a pilot randomized double-blind-controlled trial
- Sanjeev Kumar, Reza Zomorrodi, Zaid Ghazala, Michelle S. Goodman, Daniel M. Blumberger, Zafiris J. Daskalakis, Corinne E. Fischer, Benoit H. Mulsant, Bruce G. Pollock, Tarek K. Rajji
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- Journal:
- International Psychogeriatrics / Volume 35 / Issue 3 / March 2023
- Published online by Cambridge University Press:
- 16 November 2020, pp. 143-155
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- Article
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Design:
Pilot randomized double-blind-controlled trial of repetitive paired associative stimulation (rPAS), a paradigm that combines transcranial magnetic stimulation (TMS) of the dorsolateral prefrontal cortex (DLPFC) with peripheral median nerve stimulation.
Objectives:To study the impact of rPAS on DLPFC plasticity and working memory performance in Alzheimer’s disease (AD).
Methods:Thirty-two patients with AD (females = 16), mean (SD) age = 76.4 (6.3) years were randomized 1:1 to receive a 2-week (5 days/week) course of active or control rPAS. DLPFC plasticity was assessed using single session PAS combined with electroencephalography (EEG) at baseline and on days 1, 7, and 14 post-rPAS. Working memory and theta–gamma coupling were assessed at the same time points using the N-back task and EEG.
Results:There were no significant differences between the active and control rPAS groups on DLPFC plasticity or working memory performance after the rPAS intervention. There were significant main effects of time on DLPFC plasticity, working memory, and theta–gamma coupling, only for the active rPAS group. Further, on post hoc within-group analyses done to generate hypotheses for future research, as compared to baseline, only the rPAS group improved on post-rPAS day 1 on all three indices. Finally, there was a positive correlation between working memory performance and theta–gamma coupling.
Conclusions:This study did not show a beneficial effect of rPAS for DLPFC plasticity or working memory in AD. However, post hoc analyses showed promising results favoring rPAS and supporting further research on this topic. (Clinicaltrials.gov-NCT01847586)
Contributors
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- By Douglas L. Arnold, Laura J. Balcer, Amit Bar-Or, Sergio E. Baranzini, Frederik Barkhof, Robert A. Bermel, Francois A. Bethoux, Dennis N. Bourdette, Richard K. Burt, Peter A. Calabresi, Zografos Caramanos, Tanuja Chitnis, Stacey S. Cofield, Jeffrey A. Cohen, Nadine Cohen, Alasdair J. Coles, Devon Conway, Stuart D. Cook, Gary R. Cutter, Peter J. Darlington, Ann Dodds-Frerichs, Ranjan Dutta, Gilles Edan, Michelle Fabian, Franz Fazekas, Massimo Filippi, Elizabeth Fisher, Paulo Fontoura, Corey C. Ford, Robert J. Fox, Natasha Frost, Alex Z. Fu, Siegrid Fuchs, Kazuo Fujihara, Kristin M. Galetta, Jeroen J.G. Geurts, Gavin Giovannoni, Nada Gligorov, Ralf Gold, Andrew D. Goodman, Myla D. Goldman, Jenny Guerre, Stephen L. Hauser, Peter B. Imrey, Douglas R. Jeffery, Stephen E. Jones, Adam I. Kaplin, Michael W. Kattan, B. Mark Keegan, Kyle C. Kern, Zhaleh Khaleeli, Samia J. Khoury, Joep Killestein, Soo Hyun Kim, R. Philip Kinkel, Stephen C. Krieger, Lauren B. Krupp, Emmanuelle Le Page, David Leppert, Scott Litwiller, Fred D. Lublin, Henry F. McFarland, Joseph C. McGowan, Don Mahad, Jahangir Maleki, Ruth Ann Marrie, Paul M. Matthews, Francesca Milanetti, Aaron E. Miller, Deborah M. Miller, Xavier Montalban, Charity J. Morgan, Ichiro Nakashima, Sridar Narayanan, Avindra Nath, Paul W. O’Connor, Jorge R. Oksenberg, A. John Petkau, Michael D. Phillips, J. Theodore Phillips, Tammy Phinney, Sean J. Pittock, Sarah M. Planchon, Chris H. Polman, Alexander Rae-Grant, Stephen M. Rao, Stephen C. Reingold, Maria A. Rocca, Richard A. Rudick, Amber R. Salter, Paula Sandler, Jaume Sastre-Garriga, John R. Scagnelli, Dana J. Serafin, Lynne Shinto, Nancy L. Sicotte, Jack H. Simon, Per Soelberg Sørensen, Ryan E. Stagg, James M. Stankiewicz, Lael A. Stone, Amy Sullivan, Matthew Sutliff, Jessica Szpak, Alan J. Thompson, Bruce D. Trapp, Helen Tremlett, Maria Trojano, Orla Tuohy, Rhonda R. Voskuhl, Marc K. Walton, Mike P. Wattjes, Emmanuelle Waubant, Martin S. Weber, Howard L Weiner, Brian G. Weinshenker, Bianca Weinstock-Guttman, Jeffrey L. Winters, Jerry S. Wolinsky, Vijayshree Yadav, E. Ann Yeh, Scott S. Zamvil
- Edited by Jeffrey A. Cohen, Richard A. Rudick
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- Book:
- Multiple Sclerosis Therapeutics
- Published online:
- 05 December 2011
- Print publication:
- 20 October 2011, pp viii-xii
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