Abnormal cholesterol is associated with prefrontal white matter abnormalities among obese adults, a diffusion tensor imaging study

Abstract

The brain is the most cholesterol-rich organ in the body. Although most of the cholesterol in the brain is produced endogenously, some studies suggest that systemic cholesterol may be able to enter the brain. We investigated whether abnormal cholesterol profiles correlated with diffusion-tensor-imaging-based estimates of white matter microstructural integrity of lean and overweight/obese (o/o) adults. Twenty-two lean and 39 obese adults underwent magnetic resonance imaging, kept a 3-day food diary, and had a standardized assessment of fasting blood lipids. The lean group ate less cholesterol rich food than o/o although both groups ate equivalent servings of food per day. Voxelwise correlational analyses controlling for age, diabetes, and white matter hyperintensities, resulted in two significant clusters of negative associations between abnormal cholesterol profile and fractional anisotropy, located in the left and right prefrontal lobes. When the groups were split, the lean subjects showed no associations, whereas the o/o group expanded the association to three significant clusters, still in the frontal lobes. These findings suggest that cholesterol profile abnormalities may explain some of the reductions in white matter microstructural integrity that are reported in obesity.

Figure 1. Generation of images for voxel wise analysis

This is a pictorial depiction of how the originally acquired MR images were processed into a format where voxel wise analysis was possible. Rectangles represent images, italicized words represent procedures and diamonds represent the output from the procedures. Diffusion tensor imaging (DTI); Montreal Neurological Institute (MNI); magnetization-prepared rapid acquisition gradient echo (MPRAGE); fast fluid-attenuated inversion recovery (FLAIR); fractional anisotropy (FA); white matter (WM).

Figure 2. Differences in consumption of cholesterol rich foods in o/o and lean adults

The total number of (A) cholesterol rich foods (meat, dairy, fried food and fast food) and (B) total food consumed per day was quantified. Values represent means ± SEM. Values with (*) are significantly different, p<0.05.

Figure 3. Brain regions showing clusters of association between DTI FA and abnormal cholesterol profile among o/o individuals

Each column represents the 3 orthogonal orientations (axial, coronal, sagittal) for the significant inverse correlation clusters (analysis controlling for age, diabetes diagnosis and white matter hyperintensities; minimum cluster size is 100 voxels; p<0.001) overlaid on the normalized average T1 target image. The color bar represents the strength of the correlations.