Metabolic Syndrome Score is Associated with Lower Myelin in Cognitively Healthy Adults

Abstract

AbstractBackgroundMetabolic syndrome (MetS) is a cluster of cardiovascular risk factors, including abdominal obesity, glucose intolerance, elevated blood pressure (BP), and dyslipidemia. MetS is a known risk factor for cognitive dysfunction and dementia (Yaffe et al., 2004. YAMA), and has been linked to brain atrophy and altered WM microstructure measured with diffusion tensor MR (Alfaro et al., 2018, Metabolism). The metabolic cost of myelin maintenance makes WM particularly vulnerable to metabolic dysfunction. Here, we aim to explore the relationships between MetS and myelin, as well as test whether WC‐myelin association (Bouhrara et al., 2021, Int J Obes) is independent from systolic BP.MethodSample included 90 cognitively and neurologically healthy adults (Bookheimer et al., 2019, Neuroimage), aged 20 to 79 (M = 53, SD = 17) with 76% women. Additional exclusion criteria included systolic blood pressure >140, BMI>33, and >2 on modified Hachinski Ischemic Scale. Myelin water imaging was collected using a 3T Siemens Skyra with a 32‐channel coil and 3D‐gradient and spin‐echo (GRASE) sequence (1.9×1.9×4mm, TR = 1000ms, echoes = 32, first echo = 10ms, echo spacing = 10ms). Myelin Water Fraction maps were nonlinearly aligned to FMRIB58_FA using TBSS in FSL. MetS score was calculated as a sum of z‐scored waist circumference (WC), systolic BP, BMI, and self‐reports history of elevated cholesterol and glucose.ResultA linear regression analysis with MWF as the dependent variable, adjusting for sex, race, ethnicity, age, and age2, income and education, indicated that greater MetS score was associated with lower MWF in several regions including the genu corpus callosum, anterior corona radiata, and external capsule. WC was negatively associated with whole WM MWF (B = ‐.265, t(79,9) = ‐2.150, p = 0.035) after controlling for the above covariates and systolic BP.ConclusionAssociations between MetS with myelin content were detected especially in the late‐myelinating regions. This aligns with the development‐to‐degeneration hypothesis of WM aging, with lower oligodendrocyte‐to‐axon ratio as a possible factor contributing to metabolic vulnerability of late‐myelinating tracts. We also replicated the WC‐myelin association, although in fewer regions and with smaller effects sizes. Together, our results suggest that different metabolic syndrome components may exert both additive/synergistic, and independent effects on myelin integrity across adulthood.