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ORIGINAL RESEARCH article

Front. Neurol.
Sec. Dementia and Neurodegenerative Diseases
Volume 15 - 2024 | doi: 10.3389/fneur.2024.1452930
This article is part of the Research Topic Exploring Myelin Dynamics and White Matter Integrity in Dementia: A Path Towards Innovative Therapies View all articles

Spectris TM Treatment Preserves Corpus Callosum Structure in Alzheimer's Disease Running Head: Preserving Corpus Callosum Structure in AD

Provisionally accepted
Xiao Da Xiao Da 1*Evan Hempel Evan Hempel 1*Adam M. Brickman Adam M. Brickman 2Mihály Hajós Mihály Hajós 1*Ralph Kern Ralph Kern 1*Aylin Cimenser Aylin Cimenser 1*
  • 1 Cognito Therapeutics, Inc., Cambridge, United States
  • 2 Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, New York, New York, United States

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

    Objective: To examine the impact of 40Hz gamma stimulation on the preservation of the corpus callosum, a critical structure for interhemispheric connectivity, in people with mild cognitive impairment or Alzheimer's Disease.Methods: OVERTURE (NCT03556280) participants were randomized 2:1 (Active:Sham) to receive daily, 1-hour, 40-Hz gamma sensory stimulation or sham treatment for six months.Structural magnetic resonance imaging data were analyzed to assess changes in corpus callosum area (N=50; 33 for active, 17 for sham). Bayesian linear mixed-effects modeling was used to assess differences in longitudinal changes of corpus callosum area between the two treatment groups.Results: All observed differences in corpus callosum area favored the active treatment group.Differences were observed in the total corpus callosum area (2.28±0.87%, p<0.02) and its subregions, including genu/rostrum (2.36±0.90%, p<0.02), anterior-body (2.64±1.26%, p<0.04), mid-body (2.79±1.18%, p<0.03), posterior-body (2.87±1.41%, p<0.05), and splenium (1.58±0.73%, p<0.04). Total corpus callosum area and some of the sub-regional differences, such as genu/rostrum and splenium, were observed as early as 3 months after commencement of treatment.The structural magnetic resonance imaging results from the OVERTURE Phase 2 study suggest that six months of non-invasive 40Hz stimulation reduces the rate of atrophy of the corpus callosum in individuals with Alzheimer's Disease. The preservation of structural integrity in the corpus callosum, crucial for interhemispheric communication and cognitive function, may be achievable through this non-invasive approach, potentially providing a promising disease-modifying alternative in Alzheimer's Disease management.

    Keywords: Alzheimer's disease, Corpus Callosum, white matter, Atrophy, 40Hz, non-invasive, gamma, stimulation

    Received: 21 Jun 2024; Accepted: 10 Sep 2024.

    Copyright: © 2024 Da, Hempel, Brickman, Hajós, Kern and Cimenser. 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:
    Xiao Da, Cognito Therapeutics, Inc., Cambridge, United States
    Evan Hempel, Cognito Therapeutics, Inc., Cambridge, United States
    Mihály Hajós, Cognito Therapeutics, Inc., Cambridge, United States
    Ralph Kern, Cognito Therapeutics, Inc., Cambridge, United States
    Aylin Cimenser, Cognito Therapeutics, Inc., Cambridge, 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.