Ceramides predict verbal memory performance in coronary artery disease patients undertaking exercise: A prospective cohort pilot study

Background: Coronary artery disease (CAD) is associated with verbal memory decline, although deterioration may be mitigated in individuals undertaking exercise interventions. Ceramide sphingolipids, suggested to play a role in pathological neurodegeneration, have been associated with the development and progression of CAD but their relationship with cognitive response to exercise has not been assessed. In this study, concentrations of very long chain ceramides (C22:0 and C24:0) were assessed as predictors of changes in verbal memory performance over 1 year in subjects with CAD undertaking cardiac rehabilitation (CR). Methods. Verbal memory was measured using the California Verbal Learning Test 2^nd Ed. (CVLT-II), from which Z-scores were calculated based on age, gender and education matched norms. Baseline plasma C22:0 and C24:0 ceramide concentrations were measured from fasting blood samples using high performance liquid chromatography coupled electrospray ionization tandem mass spectrometry (LC/MS/MS). Repeated measures general linear models were used to determine the association between baseline plasma ceramides and the change in verbal memory performance over 1 year of CR controlling for age and body mass index (BMI). Results: In patients with CAD (n = 33, mean age = 62 ± 9 years, 84.8% male, years of education = 17 ± 3 years), higher baseline plasma C22:0 (F_{1, 29} = 5.30, p = 0.03) and C24:0 (F _{1, 29} = 4.04, p = 0.05) concentrations significantly predicted less improvement in verbal memory performance over 1 year of CR controlling for age and BMI. Conclusions: Plasma ceramide concentrations should be further examined as potential predictors of cognitive response to exercise and worse cognitive outcomes in patients with CAD. Trial registration. NCT01625754.