Elevated body-mass index is associated with reduced white matter integrity in two large independent cohorts

Obesity has been associated with a variety of neurobiological alterations. Recent neuroimaging research has pointed to the relevance of brain structural and functional alterations in the development of obesity. However, while the role of gray matter atrophy in obesity has been evidenced in several well powered studies, large scale evidence for altered white matter integrity in obese subjects is still absent. With this study, we therefore aimed to investigate potential associations between white matter abnormalities and body mass index (BMI) in two large independent samples of healthy adults. Associations between BMI values and whole brain fractional anisotropy (FA) were investigated in two independent cohorts: A sample of n = 369 healthy subjects from the Munster Neuroimaging Cohort (MNC), as well as a public available sample of n = 1064 healthy subjects of the Humane Connectome Project (HCP) were included in the present study. Tract based spatial statistics (TBSS) analyses of BMI on whole brain FA were conducted including age and sex as nuisance covariates using the FMRIB library (FSL Version 5.0). Threshold-free cluster enhancement was applied to control for multiple comparisons. In both samples higher BMI was significantly associated with strong and widespread FA reductions. These effects were most pronounced in the corpus callosum, bilateral posterior thalamic radiation, bilateral internal capsule and external capsule, bilateral inferior longitudinal fasciculus and inferior fronto-occipital fasciculus. The association was found to be independent of age, sex and other cardiovascular risk factors. No significant positive associations between BMI and FA occurred. With this highly powered study, we provide robust evidence for globally reduced white matter integrity associated with elevated BMI including replication in an independent sample. The present work thus points out the relevance of white matter alterations as a neurobiological correlate of obesity.