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BRIEF RESEARCH REPORT article

Front. Neurosci.
Sec. Neurodegeneration
Volume 18 - 2024 | doi: 10.3389/fnins.2024.1492428

Open label Pilot of Personalized, Neuroimaging-Guided Theta Burst Stimulation in Early-Stage Alzheimer's Disease

Provisionally accepted
Bhavani Kashyap Bhavani Kashyap 1,2*Leah R Hanson Leah R Hanson 1,2Sally K Gustafson Sally K Gustafson 1Terry R Barclay Terry R Barclay 1,2Clarissa M Howe Clarissa M Howe 1,2Samantha J Sherman Samantha J Sherman 1,2Marcel Hungs Marcel Hungs 2Michael H Rosenbloom Michael H Rosenbloom 3
  • 1 HealthPartners Institute, Bloomington, United States
  • 2 HealthPartners Center for Memory and Aging, St Paul, MN, United States
  • 3 UW Medicine Memory and Brain Wellness Center, Seattle, California, United States

The final, formatted version of the article will be published soon.

    Background: Alzheimer's disease (AD) is characterized by cerebral amyloid plaques and neurofibrillary tangles and disruption of large-scale brain networks (LSBNs). Transcranial magnetic stimulation (TMS) has emerged as a potential non-invasive AD treatment that may serve as an adjunct therapy with FDA approved medications.We conducted a 10-subject open label, single site study evaluating the effect of functional connectivity-resting state functional MRI guided-approach to TMS targeting with dysfunctional LSBNs in subjects with biomarker-confirmed early-stage AD (https://clinicaltrials.gov/study/NCT05292222). Subjects underwent pre-post imaging and testing to assess connectivity dysfunction and cognition. All participants received intermittent theta burst stimulation ([iTBS], [80% motor threshold; 5 sessions per day; 5 days; 3 targets; 18,000 pulses/day]) over 2 weeks. Three Human Connectome Project (HCP) defined parcellations were targeted, with one common [right temporal area G dorsal (RTGd)] target across all subjects and two personalized.We identified the following parcellations to be dysfunctional: RTGd, left area 8A ventral (L8Av), left area 8B lateral (L8BL), and left area 55b (L55b). There were no changes in these parcellations after treatment, but subjects showed improvement on the Repeatable Battery for the Assessment of Neuropsychological Status attention index (9.7; p=0.01). No subject dropped out of the treatment, though 3 participants were unable to tolerate the RTGd target due to facial twitching (n=2) and anxiety (n=1).Accelerated iTBS protocol was well-tolerated and personalized target-based treatment is feasible in early-stage AD. Further sham-controlled clinical trials are necessary to determine if this is an effective adjunctive treatment in early-stage AD.

    Keywords: Transcranial magnetic stimulation (TMS), Clinical Trial, functional connectivity (FC), large-scale brain networks, Human Connectome Project (HCP)

    Received: 06 Sep 2024; Accepted: 21 Nov 2024.

    Copyright: © 2024 Kashyap, Hanson, Gustafson, Barclay, Howe, Sherman, Hungs and Rosenbloom. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Bhavani Kashyap, HealthPartners Institute, Bloomington, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.