Lipid Metabolism, Abdominal Adiposity, and Cerebral Health in the Amish

Abstract

Objective: To assess the association between peripheral lipid/fat profiles and cerebral gray matter (GM) and white matter (WM) in healthy Old Order Amish (OOA). Methods: Blood lipids, abdominal adiposity, liver lipid contents, and cerebral microstructure were assessed in OOA (N = 64, 31 males/33 females, ages 18-77). Orthogonal factors were extracted from lipid and imaging adiposity measures. GM assessment used the Human Connectome Project protocol to measure whole-brain average cortical thickness. Diffusion-weighted imaging was used to derive WM fractional anisotropy and kurtosis anisotropy measurements. Results: Lipid/fat measures were captured by three orthogonal factors explaining 80% of the variance. Factor one loaded on cholesterol and/or low-density lipoprotein cholesterol measurements; factor two loaded on triglyceride/liver measurements; and factor three loaded on abdominal fat measurements. A two-stage regression including age/sex (first stage) and the three factors (second stage) examined the peripheral lipid/fat effects. Factors two and three significantly contributed to WM measures after Bonferroni corrections (P < 0.007). No factor significantly contributed to GM. Blood pressure (BP) inclusion did not meaningfully alter the lipid/fat-WM relationship. Conclusions: Peripheral lipid/fat indicators were significantly and negatively associated with cerebral WM rather than with GM, independent of age and BP level. Dissecting the fat/lipid components contributing to different brain imaging parameters may open a new understanding of the body-brain connection through lipid metabolism.