Lipid Metabolism, Abdominal Adiposity and Cerebral Health in the Amish

OBJECTIVE: To assess the association between peripheral lipid/fat profiles and cerebral grey 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 derived WM fractional anisotropy and kurtosis anisotropy measurements. RESULTS: Lipid/fat measures were captured by three orthogonal factors explaining 80% of the variance. Factor 1 loaded on cholesterol/LDL-C; Factor 2 on triglyceride/liver measurements; Factor 3 on abdominal fat measurements. A two-stage regression including age/sex (1(st) stage) and the three factors (2(nd) stage) examined the peripheral lipid/fat effects. Factors 2 and 3 significantly contributed to WM measures after Bonferroni corrections (p<0.007). No factor significantly contributed to GM. Blood pressure inclusion did not meaningfully alter the lipid/fat-WM relationship. CONCLUSIONS: Peripheral lipid/fat indicators significantly and negatively associated with cerebral WM rather than GM, independent of age and blood pressure. Dissecting the fat/lipid components contributing to different brain imaging parameters may open a new understanding of the body-brain connection through lipid metabolism.