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.
-
The Cambridge Centre for Ageing and NeuroscienceStructural and functional MRI, MEG, and cognitive data from a cross-sectional adult lifespan sample.
-
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.
Metrics
-
- 6,844
- views
-
- 676
- downloads
-
- 4
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
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
-
- Epidemiology and Global Health
Background:
Circulating omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) have been associated with various chronic diseases and mortality, but results are conflicting. Few studies examined the role of omega-6/omega-3 ratio in mortality.
Methods:
We investigated plasma omega-3 and omega-6 PUFAs and their ratio in relation to all-cause and cause-specific mortality in a large prospective cohort, the UK Biobank. Of 85,425 participants who had complete information on circulating PUFAs, 6461 died during follow-up, including 2794 from cancer and 1668 from cardiovascular disease (CVD). Associations were estimated by multivariable Cox proportional hazards regression with adjustment for relevant risk factors.
Results:
Risk for all three mortality outcomes increased as the ratio of omega-6/omega-3 PUFAs increased (all Ptrend <0.05). Comparing the highest to the lowest quintiles, individuals had 26% (95% CI, 15–38%) higher total mortality, 14% (95% CI, 0–31%) higher cancer mortality, and 31% (95% CI, 10–55%) higher CVD mortality. Moreover, omega-3 and omega-6 PUFAs in plasma were all inversely associated with all-cause, cancer, and CVD mortality, with omega-3 showing stronger effects.
Conclusions:
Using a population-based cohort in UK Biobank, our study revealed a strong association between the ratio of circulating omega-6/omega-3 PUFAs and the risk of all-cause, cancer, and CVD mortality.
Funding:
Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institute of Health under the award number R35GM143060 (KY). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
-
- Ecology
- Epidemiology and Global Health
Non-pharmaceutical interventions implemented to block SARS-CoV-2 transmission in early 2020 led to global reductions in the incidence of invasive pneumococcal disease (IPD). By contrast, most European countries reported an increase in antibiotic resistance among invasive Streptococcus pneumoniae isolates from 2019 to 2020, while an increasing number of studies reported stable pneumococcal carriage prevalence over the same period. To disentangle the impacts of the COVID-19 pandemic on pneumococcal epidemiology in the community setting, we propose a mathematical model formalizing simultaneous transmission of SARS-CoV-2 and antibiotic-sensitive and -resistant strains of S. pneumoniae. To test hypotheses underlying these trends five mechanisms were built into the model and examined: (1) a population-wide reduction of antibiotic prescriptions in the community, (2) lockdown effect on pneumococcal transmission, (3) a reduced risk of developing an IPD due to the absence of common respiratory viruses, (4) community azithromycin use in COVID-19 infected individuals, (5) and a longer carriage duration of antibiotic-resistant pneumococcal strains. Among 31 possible pandemic scenarios involving mechanisms individually or in combination, model simulations surprisingly identified only two scenarios that reproduced the reported trends in the general population. They included factors (1), (3), and (4). These scenarios replicated a nearly 50% reduction in annual IPD, and an increase in antibiotic resistance from 20% to 22%, all while maintaining a relatively stable pneumococcal carriage. Exploring further, higher SARS-CoV-2 R0 values and synergistic within-host virus-bacteria interaction mechanisms could have additionally contributed to the observed antibiotic resistance increase. Our work demonstrates the utility of the mathematical modeling approach in unraveling the complex effects of the COVID-19 pandemic responses on AMR dynamics.
