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Peripheral sphingolipids are associated with variation in white matter microstructure in older adults.

ABSTRACT: Sphingolipids serve important structural and functional roles in cellular membranes and myelin sheaths. Plasma sphingolipids have been shown to predict cognitive decline and Alzheimer's disease. However, the association between plasma sphingolipid levels and brain white matter (WM) microstructure has not been examined. We investigated whether plasma sphingolipids (ceramides and sphingomyelins) were associated with magnetic resonance imaging-based diffusion measures, fractional anisotropy (FA), and mean diffusivity, 10.5 years later in 17 WM regions of 150 cognitively normal adults (mean age 67.2). Elevated ceramide species (C20:0, C22:0, C22:1, and C24:1) were associated with lower FA in multiple WM regions, including total cerebral WM, anterior corona radiata, and the cingulum of the cingulate gyrus. Higher sphingomyelins (C18:1 and C20:1) were associated with lower FA in regions such as the anterior corona radiata and body of the corpus callosum. Furthermore, lower sphingomyelin to ceramide ratios (C22:0, C24:0, and C24:1) were associated with lower FA or higher mean diffusivity in regions including the superior and posterior corona radiata. However, although these associations were significant at the a priori p < 0.05, only associations with some regional diffusion measures for ceramide C22:0 and sphingomyelin C18:1 survived correction for multiple comparisons. These findings suggest plasma sphingolipids are associated with variation in WM microstructure in cognitively normal aging.

SUBMITTER: Gonzalez CE

PROVIDER: S-EPMC4894643 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Peripheral sphingolipids are associated with variation in white matter microstructure in older adults.

Gonzalez Christopher E CE Venkatraman Vijay K VK An Yang Y Landman Bennett A BA Davatzikos Christos C Ratnam Bandaru Veera Venkata VV Haughey Norman J NJ Ferrucci Luigi L Mielke Michelle M MM Resnick Susan M SM

Neurobiology of aging 20160421

Sphingolipids serve important structural and functional roles in cellular membranes and myelin sheaths. Plasma sphingolipids have been shown to predict cognitive decline and Alzheimer's disease. However, the association between plasma sphingolipid levels and brain white matter (WM) microstructure has not been examined. We investigated whether plasma sphingolipids (ceramides and sphingomyelins) were associated with magnetic resonance imaging-based diffusion measures, fractional anisotropy (FA), a ...[more]

PMID: 27255825

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Project description:White matter structure declines with advancing age and has been associated with a decline in memory and executive processes in older adulthood. Yet, recent research suggests that higher physical activity and fitness levels may be associated with less white matter degeneration in late life, although the tract-specificity of this relationship is not well understood. In addition, these prior studies infrequently associate measures of white matter microstructure to cognitive outcomes, so the behavioral importance of higher levels of white matter microstructural organization with greater fitness levels remains a matter of speculation. Here we tested whether cardiorespiratory fitness (VO2max) levels were associated with white matter microstructure and whether this relationship constituted an indirect pathway between cardiorespiratory fitness and spatial working memory in two large, cognitively and neurologically healthy older adult samples. Diffusion tensor imaging was used to determine white matter microstructure in two separate groups: Experiment 1, N=113 (mean age=66.61) and Experiment 2, N=154 (mean age=65.66). Using a voxel-based regression approach, we found that higher VO2max was associated with higher fractional anisotropy (FA), a measure of white matter microstructure, in a diverse network of white matter tracts, including the anterior corona radiata, anterior internal capsule, fornix, cingulum, and corpus callosum (PFDR-corrected<.05). This effect was consistent across both samples even after controlling for age, gender, and education. Further, a statistical mediation analysis revealed that white matter microstructure within these regions, among others, constituted a significant indirect path between VO2max and spatial working memory performance. These results suggest that greater aerobic fitness levels are associated with higher levels of white matter microstructural organization, which may, in turn, preserve spatial memory performance in older adulthood.

Dataset Information

Peripheral sphingolipids are associated with variation in white matter microstructure in older adults.

Publications

Peripheral sphingolipids are associated with variation in white matter microstructure in older adults.

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