Central obesity is selectively associated with cerebral gray matter atrophy in 15,634 subjects in the UK Biobank

Abstract

Background: Obesity is a risk factor for both cardiovascular disease and dementia, but the mechanisms underlying this association are not fully understood. We examined associations between obesity, including estimates of central obesity using different modalities, with brain gray matter (GM) volume in the UK Biobank, a large population-based cohort study.

Methods: To determine relationships between obesity and the brain we used brain MRI, abdominal MRI, dual-energy X-ray absorptiometry (DXA), and bioelectric whole-body impedance. We determined whether obesity was associated with any change in brain gray matter (GM) and white matter (WM) volumes, and brain network efficiency derived from the structural connectome (wiring of the brain) as determined from diffusion-tensor MRI tractography. Using Waist-Hip Ratio (WHR), abdominal MRI and DXA we determined whether any associations were primarily with central rather than peripheral obesity, and whether associations were mediated by known cardiovascular risk factors. We analyzed brain MRI data from 15,634.

Results: We found that central obesity, was associated with decreased GM volume (anthropometric data: p = 6.7 × 10^-16, DXA: p = 8.3 × 10^-81, abdominal MRI: p = 0.0006). Regional associations were found between central obesity and with specific GM subcortical nuclei (thalamus, caudate, pallidum, nucleus accumbens). In contrast, no associations were found with WM volume or structure, or brain network efficiency. The effects of central obesity on GM volume were not mediated by C-reactive protein or blood pressure, glucose, lipids.

Conclusions: Central body-fat distribution rather than the overall body-fat percentage is associated with gray matter changes in people with obesity. Further work is required to identify the factors that mediate the association between central obesity and GM atrophy.

Fig. 1. Association between BMI and WHR with GM and WM volumes, WMH and brain network measures (global and local efficiency).

Significant differences across the stratified BMI and WHR groups are present for GM volume and WMH but not for WM volumes or network measures. (Error bars show standard deviations, boxes correspond to the interquartile range.).

Fig. 2. Scatter plots showing the significant negative effect of whole-body fat-free mass and whole-body fat mass on the normalized cerebral GM volume.

Pearson r in these figures corresponds to the overall effect size of whole-body fat-free/fat mass on cerebral GM volume before correction for the covariates.

Fig. 3. Associations between indicators of body composition from abdominal MRI and normalized GM volume.

Visceral adipose tissue volume (normalized by body weight), abdominal subcutaneous adipose tissue volume, total adipose tissue volume and total lean tissue volume (normalized by body weight), derived from abdominal MRI, as predictors of normalized cerebral GM volume. Pearson r in these figures corresponds to the overall effect size of the association before correction for the covariates.