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

Chris-Patrick Pflanz,Sadaf Farooqi,Eric L Harshfield,Jonathan Tay,Daniel J Tozer,Hugh S Markus

doi:10.1038/s41366-021-00992-2

Chris-Patrick Pflanz, Sadaf Farooqi + Show 4 more

Open Access

https://doi.org/10.1038/s41366-021-00992-2

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Abstract

BackgroundObesity 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.MethodsTo 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.ResultsWe 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.ConclusionsCentral 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.

Highlights

Obesity is defined as an excess of body fat that adversely effects health and is rising in prevalence globally
No interaction with gender was found for android-to-gynoid fat mass ratio, trunk-to-leg fat mass ratio, or trunk-to-leg lean mass ratio. In this large population-based study, central obesity was associated with lower gray matter (GM) volume, but not with white matter (WM) volume or brain network integrity
We assessed central obesity using a variety of techniques including Waist-Hip Ratio (WHR), visceral adipose tissue from abdominal MRI, dual-energy X-ray absorptiometry (DXA), and bioelectrical impedance

Summary

Introduction

Obesity is defined as an excess of body fat that adversely effects health and is rising in prevalence globally. More recent research used diffusion-tensor MRI tractography to reconstruct the connectome (characteristic wiring of the human brain at the mesoscale), and derived measures of brain network integrity that essentially indicate the robustness of the connectome against fault These network metrics have been shown to correlate better with cognition than macrostructural WM volume, or WM hyperintensities (WMH) in both normal ageing [7] and disease states [8] and might be a more sensitive marker of white matter damage in obesity. 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.

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Conclusion