The Health & Nutrition Innovative International Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel; Department of Internal Medicine D, Chaim Sheba Medical Center, Ramat-Gan, Israel
Anat Yaskolka Meir
The Health & Nutrition Innovative International Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
Ehud Rinott
The Health & Nutrition Innovative International Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
Gal Tsaban
The Health & Nutrition Innovative International Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
Hila Zelicha
The Health & Nutrition Innovative International Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
Matthias Blüher
Department of Medicine, University of Leipzig, Leipzig, Germany
Uta Ceglarek
Department of Medicine, University of Leipzig, Leipzig, Germany
Michael Stumvoll
Department of Medicine, University of Leipzig, Leipzig, Germany
Ilan Shelef
Department of Diagnostic Imaging, Soroka Medical Center, Beer Sheva, Israel
Department of Psychology, Ben-Gurion University of the Negev, Beer Sheva, Israel
Iris Shai
The Health & Nutrition Innovative International Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel; Department of Medicine, University of Leipzig, Leipzig, Germany; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, United States
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 Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed Study (DIRECT-PLUS) trial, we tested the effect of weight loss following 18 months of lifestyle intervention on predicted brain age based on magnetic resonance imaging (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 18 months 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 09933838 SFB 105 (to I Shai).
