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Original research
A phase I trial of accelerated intermittent theta burst rTMS for amnestic MCI
  1. Stephanie Aghamoosa1,2,
  2. James Lopez3,
  3. Katrina Rbeiz4,
  4. Holly H Fleischmann3,
  5. Olivia Horn4,
  6. Katrina Madden4,
  7. Kevin A Caulfield2,3,
  8. Michael U Antonucci5,
  9. Gonzalo Revuelta4,
  10. Lisa M McTeague2,3,6,
  11. Andreana Benitez2,4
  1. 1Health Sciences and Research, Medical University of South Carolina, Charleston, South Carolina, USA
  2. 2Center for Biomedical Imaging, Medical University of South Carolina, Charleston, South Carolina, USA
  3. 3Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina, USA
  4. 4Neurology, Medical University of South Carolina, Charleston, South Carolina, USA
  5. 5Radiological Science, Medical University of South Carolina, Charleston, South Carolina, USA
  6. 6Ralph H. Johnson VA Health Care System, Charleston, South Carolina, USA
  1. Correspondence to Dr Stephanie Aghamoosa, Health Sciences and Research, Medical University of South Carolina, Charleston, SC 29425, USA; fountast{at}musc.edu

Abstract

Background Emerging evidence suggests that repetitive transcranial magnetic stimulation (rTMS) enhances cognition in mild cognitive impairment (MCI). Accelerated intermittent theta burst stimulation (iTBS) rTMS protocols are promising as they substantially reduce burden by shortening the treatment course, but the safety, feasibility, and acceptability of iTBS have not been established in MCI.

Methods 24 older adults with amnestic MCI (aMCI) due to possible Alzheimer’s disease enrolled in a phase I trial of open-label accelerated iTBS to the left dorsolateral prefrontal cortex (8 stimulation sessions of 600 pulses of iTBS/day for 3 days). Participants rated common side effects during and after each session and retrospectively (at post-treatment and 4-week follow-up). They completed brain MRI (for safety assessments and electric field modeling), neuropsychiatric evaluations, and neuropsychological testing before and after treatment; a subset of measures was administered at follow-up.

Results Retention was high (95%) and there were no adverse neuroradiological, neuropsychiatric, or neurocognitive effects of treatment. Participants reported high acceptability, minimal side effects, and low desire to quit despite some rating the treatment as tiring. Electric field modeling data suggest that all participants received safe and therapeutic cortical stimulation intensities. We observed a significant, large effect size (d=0.98) improvement in fluid cognition using the NIH Toolbox Cognition Battery from pre-treatment to post-treatment.

Conclusions Our findings support the safety, feasibility, and acceptability of accelerated iTBS in aMCI. In addition, we provide evidence of target engagement in the form of improved cognition following treatment. These promising results directly inform future trials aimed at optimizing treatment parameters.

Trial registration number NCT04503096.

  • MAGNETIC STIMULATION
  • ALZHEIMER'S DISEASE
  • COGNITION

Data availability statement

No data are available. The data used in this study are not publicly available as they contain confidential clinical information and participants were not asked to consent to data sharing. Analysis code for this study may be requested from the corresponding author.

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Data availability statement

No data are available. The data used in this study are not publicly available as they contain confidential clinical information and participants were not asked to consent to data sharing. Analysis code for this study may be requested from the corresponding author.

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Footnotes

  • LMM and AB are joint senior authors.

  • X @stephA_phd

  • Contributors SA: conceptualisation, data curation, formal analysis, visualisation, writing–original draft; JL: investigation, data curation, writing–review and editing; KR: investigation, writing–review and editing; HHF: investigation, writing–review and editing; OH: investigation, writing–review and editing; KM: project administration, writing–review and editing; KAC: formal analysis, visualisation, writing–review and editing; MUA: investigation, writing–review and editing; GR: investigation, writing–review and editing; LMM: conceptualisation, methodology, resources, writing–original draft, guarantor of the paper; AB: conceptualisation, methodology, resources, writing–original draft, funding acquisition, guarantor of the paper.

  • Funding This work was supported by the National Institutes of Health National Institute on Aging (1R01AG081237-01) and National Center for Medical Rehabilitation Research (P2CHD086844 pilot project #29), the New Vision Research Foundation (NVR2020-001-3), the National Institute of General Medical Sciences (P20 GM109040) and the Alzheimer’s Association (AARF-21-850073). It was also supported, in part, by the National Center for Advancing Translational Sciences of the National Institutes of Health under grant number UL1 TR001450.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.