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

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 lifestyle intervention. In a sub-study of 102 participants of the DIRECT-PLUS (dietary-intervention-randomized-controlled-trial polyphenol-unprocessed) trial, we tested the effect of 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. 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. These results suggest that lifestyle intervention has beneficial effects on the trajectory of brain aging.