The effect of weight loss following 18 months of lifestyle intervention on brain age assessed with resting-state functional connectivity

  1. Gidon Levakov  Is a corresponding author
  2. Alon Kaplan
  3. Anat Yaskolka Meir
  4. Ehud Rinott
  5. Gal Tsaban
  6. Hila Zelicha
  7. Matthias Blüher
  8. Uta Ceglarek
  9. Michael Stumvoll
  10. Ilan Shelef
  11. Galia Avidan
  12. Iris Shai
  1. Ben-Gurion University of the Negev, Israel
  2. University of Leipzig, Germany
  3. Soroka Medical Center, Israel

Abstract

Background: Obesity negatively impacts multiple bodily systems, including the central nervous system. Retrospective studies that estimated chronological age from neuroimaging have found accelerated brain aging in obesity, but it is unclear how this estimation would be affected by weight loss following a lifestyle intervention.

Methods: In a sub-study of 102 participants of the DIRECT-PLUS (dietary-intervention-randomized-controlled-trial polyphenol-unprocessed) trial, we tested the effect of weight loss following 18 months of lifestyle intervention on predicted brain age based on MRI-assessed resting-state functional connectivity (RSFC). We further examined how dynamics in multiple health factors, including anthropometric measurements, blood biomarkers, and fat deposition, can account for changes in brain age.

Results: To establish our method, we first demonstrated that our model could successfully predict chronological age from RSFC in three cohorts (n=291;358;102). We then found that among the DIRECT-PLUS participants, 1% of body weight loss resulted in an 8.9 months attenuation of brain age. Attenuation of brain age was significantly associated with improved liver biomarkers, decreased liver fat, and visceral and deep subcutaneous adipose tissues after 18m of intervention. Finally, we showed that lower consumption of processed food, sweets, and beverages were associated with attenuated brain age.

Conclusions: Successful weight loss following lifestyle intervention might have a beneficial effect on the trajectory of brain aging.

Funding: The German Research Foundation (DFG), German Research Foundation - project number 209933838 - SFB 1052; B11), Israel Ministry of Health grant 87472511 (to I Shai); Israel Ministry of Science and Technology grant 3-13604 (to I Shai); and the California Walnuts Commission (to I Shai).

Clinical Trial: This trial was registered at clinicaltrials.gov as NCT03020186.

Data availability

The code for the brain age prediction model and the calculation of brain age attenuation is openly available online at https://github.com/GidLev/functional_brain_aging. The unprocessed data used for the model training and validation is openly available online at http://fcon_1000.projects.nitrc.org/indi/enhanced/neurodata.html for the eNKI dataset and available upon online access request https://camcan-archive.mrc-cbu.cam.ac.uk/dataaccess/ for the CamCAN dataset. Data from the DIRECT-PLUS trial is not publicly available since it contains information that could compromise the privacy of research participants. However, de-identified data could be shared upon request, subject to approval from the Soroka Medical Center Medical Ethics Board. A processed version of the data that includes participants' demographics, predicted and observed age and weight values for T0 and T18 is available as supplementary information.

The following previously published data sets were used
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    Wide array of physiological and psychological assessments, genetic information, and advanced neuroimaging.

Article and author information

Author details

  1. Gidon Levakov

    Department of Cognitive and Brain Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
    For correspondence
    gidonle@post.bgu.ac.il
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5520-3556
  2. Alon Kaplan

    Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
    Competing interests
    No competing interests declared.
  3. Anat Yaskolka Meir

    Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
    Competing interests
    No competing interests declared.
  4. Ehud Rinott

    Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
    Competing interests
    No competing interests declared.
  5. Gal Tsaban

    Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
    Competing interests
    No competing interests declared.
  6. Hila Zelicha

    Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
    Competing interests
    No competing interests declared.
  7. Matthias Blüher

    Department of Medicine, University of Leipzig, Leipzig, Germany
    Competing interests
    Matthias Blüher, has received consulting fees from Amgen, Astra Zeneca, Boehringer-Ingelheim, Bayer, Lilly, Novo Nordisk, Novartis, Sanofi and Pfizer; and fees for lectures/ presentations from Amgen, Astra Zeneca, Boehringer-Ingelheim, Bayer, Daiichi-Sankyo, Lilly, Novo Nordisk, Novartis, Sanofi and Pfizer. The author is also on the advisory board for Boehringer-Ingelheim. The author has no other competing interests to declare..
  8. Uta Ceglarek

    Department of Medicine, University of Leipzig, Leipzig, Germany
    Competing interests
    No competing interests declared.
  9. Michael Stumvoll

    Department of Medicine, University of Leipzig, Leipzig, Germany
    Competing interests
    No competing interests declared.
  10. Ilan Shelef

    Department of Diagnostic Imaging, Soroka Medical Center, Beer Sheva, Israel
    Competing interests
    No competing interests declared.
  11. Galia Avidan

    Department of Psychology, Ben-Gurion University of the Negev, Beer Sheva, Israel
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2293-3859
  12. Iris Shai

    Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
    Competing interests
    No competing interests declared.

Funding

The German Research Foundation (209933838 SFB 1052; B11)

  • Iris Shai

Israel Ministry of Health (grant 87472511)

  • Iris Shai

Israel Ministry of Science and Technology (3-13604)

  • Iris Shai

California Walnuts Commission

  • Iris Shai

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: This work was based on a sub-study of the DIREC-PLUS trial (clinicaltrials.gov ID: NCT03020186). The Soroka Medical Center Medical Ethics Board and Institutional Review Board provided ethics approval. All participants provided written consent and received no financial compensation.

Copyright

© 2023, Levakov et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Gidon Levakov
  2. Alon Kaplan
  3. Anat Yaskolka Meir
  4. Ehud Rinott
  5. Gal Tsaban
  6. Hila Zelicha
  7. Matthias Blüher
  8. Uta Ceglarek
  9. Michael Stumvoll
  10. Ilan Shelef
  11. Galia Avidan
  12. Iris Shai
(2023)
The effect of weight loss following 18 months of lifestyle intervention on brain age assessed with resting-state functional connectivity
eLife 12:e83604.
https://doi.org/10.7554/eLife.83604

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https://doi.org/10.7554/eLife.83604

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