The effect of weight loss following 18 months of lifestyle intervention on brain age assessed with resting-state functional connectivity
- Ben-Gurion University of the Negev, Israel
- University of Leipzig, Germany
- 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.
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The Cambridge Centre for Ageing and NeuroscienceStructural and functional MRI, MEG, and cognitive data from a cross-sectional adult lifespan sample.
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The NKI-Rockland sampleWide array of physiological and psychological assessments, genetic information, and advanced neuroimaging.
Article and author information
Author details
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.
Reviewing Editor
- Muthuswamy Balasubramanyam, Madras Diabetes Research Foundation, India
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.
Version history
- Preprint posted: September 21, 2022 (view preprint)
- Received: September 21, 2022
- Accepted: March 31, 2023
- Accepted Manuscript published: April 6, 2023 (version 1)
- Version of Record published: May 11, 2023 (version 2)
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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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
Further reading
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- Epidemiology and Global Health
- Microbiology and Infectious Disease
Background: Few national-level studies have evaluated the impact of 'hybrid' immunity (vaccination coupled with recovery from infection) from the Omicron variants of SARS-CoV-2.
Methods: From May 2020 to December 2022, we conducted serial assessments (each of ~4000-9000 adults) examining SARS-CoV-2 antibodies within a mostly representative Canadian cohort drawn from a national online polling platform. Adults, most of whom were vaccinated, reported viral test-confirmed infections and mailed self-collected dried blood spots to a central lab. Samples underwent highly sensitive and specific antibody assays to spike and nucleocapsid protein antigens, the latter triggered only by infection. We estimated cumulative SARS-CoV-2 incidence prior to the Omicron period and during the BA.1/1.1 and BA.2/5 waves. We assessed changes in antibody levels and in age-specific active immunity levels.
Results: Spike levels were higher in infected than in uninfected adults, regardless of vaccination doses. Among adults vaccinated at least thrice and infected more than six months earlier, spike levels fell notably and continuously for the nine months post-vaccination. By contrast, among adults infected within six months, spike levels declined gradually. Declines were similar by sex, age group, and ethnicity. Recent vaccination attenuated declines in spike levels from older infections. In a convenience sample, spike antibody and cellular responses were correlated. Near the end of 2022, about 35% of adults above age 60 had their last vaccine dose more than six months ago, and about 25% remained uninfected. The cumulative incidence of SARS-CoV-2 infection rose from 13% (95% CI 11-14%) before omicron to 78% (76-80%) by December 2022, equating to 25 million infected adults cumulatively. However, the COVID-19 weekly death rate during the BA.2/5 waves was less than half of that during the BA.1/1.1 wave, implying a protective role for hybrid immunity.
Conclusions: Strategies to maintain population-level hybrid immunity require up-to-date vaccination coverage, including among those recovering from infection. Population-based, self-collected dried blood spots are a practicable biological surveillance platform.
Funding: Funding was provided by the COVID-19 Immunity Task Force, Canadian Institutes of Health Research, Pfizer Global Medical Grants, and St. Michael's Hospital Foundation. PJ and ACG are funded by the Canada Research Chairs Program.
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- Computational and Systems Biology
- Epidemiology and Global Health
The chemical composition of foods is complex, variable, and dependent on many factors. This has a major impact on nutrition research as it foundationally affects our ability to adequately assess the actual intake of nutrients and other compounds. In spite of this, accurate data on nutrient intake are key for investigating the associations and causal relationships between intake, health, and disease risk at the service of developing evidence-based dietary guidance that enables improvements in population health. Here, we exemplify the importance of this challenge by investigating the impact of food content variability on nutrition research using three bioactives as model: flavan-3-ols, (–)-epicatechin, and nitrate. Our results show that common approaches aimed at addressing the high compositional variability of even the same foods impede the accurate assessment of nutrient intake generally. This suggests that the results of many nutrition studies using food composition data are potentially unreliable and carry greater limitations than commonly appreciated, consequently resulting in dietary recommendations with significant limitations and unreliable impact on public health. Thus, current challenges related to nutrient intake assessments need to be addressed and mitigated by the development of improved dietary assessment methods involving the use of nutritional biomarkers.
