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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

Published online by Cambridge University Press:  16 November 2020

Sanjeev Kumar ,
Reza Zomorrodi ,
Zaid Ghazala ,
Michelle S. Goodman ,
Daniel M. Blumberger ,
Zafiris J. Daskalakis ,
Corinne E. Fischer ,
Benoit H. Mulsant ,
Bruce G. Pollock  and
Tarek K. Rajji
Sanjeev Kumar
Affiliation:
Campbell Family Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada Department of Psychiatry, University of Toronto, Toronto, ON, Canada
Reza Zomorrodi
Affiliation:
Campbell Family Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada
Zaid Ghazala
Affiliation:
Campbell Family Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada Department of Psychiatry, University of Toronto, Toronto, ON, Canada
Michelle S. Goodman
Affiliation:
Campbell Family Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada
Daniel M. Blumberger
Affiliation:
Campbell Family Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada Department of Psychiatry, University of Toronto, Toronto, ON, Canada
Zafiris J. Daskalakis
Affiliation:
Campbell Family Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada Department of Psychiatry, University of Toronto, Toronto, ON, Canada
Corinne E. Fischer
Affiliation:
Department of Psychiatry, University of Toronto, Toronto, ON, Canada Keenan Research Centre for Biomedical Research, Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, ON, Canada
Benoit H. Mulsant
Affiliation:
Campbell Family Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada Department of Psychiatry, University of Toronto, Toronto, ON, Canada
Bruce G. Pollock
Affiliation:
Campbell Family Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada Department of Psychiatry, University of Toronto, Toronto, ON, Canada
Tarek K. Rajji*
Affiliation:
Campbell Family Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada Department of Psychiatry, University of Toronto, Toronto, ON, Canada
*
Correspondence should be addressed to: Dr. Tarek Rajji, MD, FRCPC, Adult Neurodevelopment and Geriatric Psychiatry Division, Centre for Addiction and Mental Health, 80 Workman Way, Toronto, ON M6J 1H4, Canada. Phone: +1 416 535 8501x33661; Fax: +1 416 583 1307. Email: Tarek.Rajji@camh.ca.
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Abstract

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)

Keywords

dementianeuroplasticitygeriatricstranscranial magnetic stimulationtheta–gamma couplingTMS-EEG
Type
Original Research Article
Information
International Psychogeriatrics , Volume 35 , Special Issue 3: Issue Theme: Thinking outside the box: later life wellbeing and functioning from new angles , March 2023 , pp. 143 - 155
Copyright
© International Psychogeriatric Association 2020

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