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

Gidon Levakov, Alon Kaplan, Anat Yaskolka Meir, Ehud Rinott, Gal Tsaban, Hila Zelicha, Matthias Blüher, Uta Ceglarek, Michael Stumvoll, Ilan Shelef, Galia Avidan, Iris Shai

Journal: eLife 2023;12():e83604

PMID: 37022140

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Plain Language Summary

Obesity is linked to premature brain ageing and subsequent development of diseases such as dementia and Alzheimer’s disease. Weight loss through lifestyle modifications may be able to attenuate brain ageing. This sub-study of 102 individuals from a randomised control trial known as the Dietary Intervention Randomised Controlled Trial Polyphenols Unprocessed Study (DIRECT-PLUS), aimed to determine the effect of 18 months lifestyle modifications and weight loss on brain age. The results showed that a decrease in BMI attenuated brain ageing and that 1% body weight loss reduced brain ageing by 8.9 months. Reduced brain age was also associated with decreased waist circumference and fat mass. Interestingly, reduced consumption of processed foods was also associated with reduced brain age. It was concluded that weight loss can be of benefit to brain health. This study could be used by healthcare professionals to understand that people with obesity are at a higher risk of brain related diseases, and that weight loss may be an effective way to prevent their development.

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 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).

Address: Department of Brain and Cognitive Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.; 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.; 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 Diagnostic Imaging, Soroka Medical Center, Beer Sheva, Israel.; Department of Psychology, Ben-Gurion University of the Negev, Beer Sheva, Israel.; 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.

DOI: 10.7554/eLife.83604