Individuals living with obesity tend to have increased brain age, reflecting poorer brain health likely due to grey and white matter atrophy related to obesity. However, it is unclear if older brain age associated with obesity can be reversed following weight loss and cardiometabolic health improvement. The aim of this study was to assess the impact of weight loss and cardiometabolic improvement following bariatric surgery on brain health, as measured by change in brain age estimated based on voxel-based morphometry (VBM) measurements. We used three distinct datasets to perform this study: 1) CamCAN dataset to train the brain age prediction model, 2) Human Connectome Project (HCP) dataset to investigate whether individuals with obesity have greater brain age than individuals with normal weight, and 3) pre-surgery, as well as 4, 12, and 24 month post-surgery data from participants (n = 87, age: 44.0 ± 9.2 years, BMI: 43.9 ± 4.2 kg/m²) who underwent a bariatric surgery to investigate whether weight loss and cardiometabolic improvement as a result of bariatric surgery lowers the brain age. As expected, our results from the HCP dataset showed a higher brain age for individuals with obesity compared to individuals with normal weight (T-value = 7.08, p-value < 0.0001). We also found significant improvement in brain health, indicated by a decrease of 2.9 and 5.6 years in adjusted delta age at 12 and 24 months following bariatric surgery compared to baseline (p-value < 0.0005 for both). While the overall effect seemed to be driven by a global change across all brain regions and not from a specific region, our exploratory analysis showed lower delta age in certain brain regions (mainly in somatomotor, visual, and ventral attention networks) at 24 months. This reduced age was also associated with post-surgery improvements in BMI, systolic/diastolic blood pressure, and HOMA-IR (T-value_BMI=4.29, T-value_SBP=4.67, T-value_DBP=4.12, T-value_HOMA-IR=3.16, all p-values < 0.05). In conclusion, these results suggest that obesity-related brain health abnormalities (as measured by delta age) might be reversed by bariatric surgery-induced weight loss and widespread improvements in cardiometabolic alterations.

Visceral adipose tissue accumulation is an important determinant of metabolic risk and can be estimated by the visceral adiposity index (VAI). Visceral adiposity may impact brain regions involved in eating behavior. We aimed to examine the association between adiposity measurements, binge eating behavior, and grey matter density. In 20 men and 59 women with severe obesity, Grey matter density was measured by voxel-based morphometry for six regions of interest associated with reward, emotion, or self-regulation: insula, orbitofrontal cortex, caudal and rostral anterior cingulate cortex (ACC), ventromedial prefrontal cortex (vmPFC), and dorsolateral prefrontal cortex (DLPFC). Binge eating behavior, depression and impulsivity was assessed by the Binge Eating Scale, Beck Depression Inventory and UPPS Impulsive Behavior Scale, respectively. Men and women were distinctively divided into two subgroups (low-VAI and high-VAI) based on the mean VAI score. Women with high-VAI were characterized by metabolic alterations, higher binge eating score and lower grey matter density in the caudal ACC compared to women with low-VAI. Men with high-VAI were characterized by a higher score for the sensation-seeking subscale of the UPPS–Impulsive Behavior Scale compared to men with low-VAI. Using a moderation–mediation analysis, we found that grey matter density in the caudal ACC mediates the association between VAI and binge eating score. In conclusion, visceral adiposity is associated with higher binge eating severity in women. Decreased grey matter density in the caudal ACC, a region involved in cognition and emotion regulation, may influence this relationship.