Sphingolipids and physical function in the Atherosclerosis Risk in Communities (ARIC) study

Long-chain sphingomyelins (SMs) may play an important role in the stability of myelin sheath underlying physical function. The objective of this study was to examine the cross-sectional and longitudinal associations of long-chain SMs [SM (41:1), SM (41:2), SM (43:1)] and ceramides [Cer (41:1) and Cer (43:1)] with physical function in the Atherosclerosis Risk in Communities (ARIC) study. Plasma concentrations of SM (41:1), SM (41:2), SM (43:1), Cer (41:1) and Cer (43:1) were measured in 389 ARIC participants in 2011-13. Physical function was assessed by grip strength, Short Physical Performance Battery (SPPB), 4-m walking speed at both 2011-13 and 2016-17, and the modified Rosow-Breslau questionnaire in 2016-2017. Multivariable linear and logistic regression analyses were performed, controlling for demographic and clinical confounders. In cross-sectional analyses, plasma concentrations of SM 41:1 were positively associated with SPPB score (β-coefficients [95% confidence internal]: 0.33 [0.02, 0.63] per 1 standard deviation [SD] increase in log-transformed concentration, p value 0.04), 4-m walking speed (0.042 m/s [0.01, 0.07], p value 0.003), and negatively with self-reported disability (odds ratio = 0.73 [0.65, 0.82], p value < 0.0001). Plasma concentrations of the five metabolites examined were not significantly associated with longitudinal changes in physical function or incidence of poor mobility. In older adults, plasma concentrations of long-chain SM 41:1 were cross-sectionally positively associated with physical function.