Ceramide Accumulation Is Associated with Declining Verbal Memory in Coronary Artery Disease Patients: An Observational Study

Abstract

Background:Biomarkers in cognitively vulnerable populations, like those with coronary artery disease (CAD), may inform earlier intervention in vascular neurodegeneration. Circulating ceramide C18:0 (CerC18:0) is associated with changes in verbal memory in early neurodegeneration and CAD progression.Objective:To investigate whether plasma CerC18:0 accumulation is associated with longitudinal declines in verbal memory performance in CAD.Methods:In addition to total CerC18:0, we assessed its relative abundance to its precursors as ratios: CerC18:0 to monohexosylceramide C18:0 (MHxCer18:0), CerC18:0 to sphingomyelin C18:0 (SM18:0), and CerC18:0 to sphingosine-1-phosphate (S1P). Verbal memory was assessed using the California Verbal Learning Test 2nd Ed. Using mixed models in 60 CAD participants, we evaluated associations between baseline CerC18:0 ratios and changes in verbal memory performance, adjusting for age, body mass index, and education. Given that cognitive decline is more rapid following onset of deficits, these associations were compared between those with possible mild vascular neurocognitive disorder (MVND).Results:Increased baseline CerC18:0 concentrations correlated with worse verbal memory performance over time (b[SE] = – 0.91[0.30], p = 0.003). Increased baseline CerC18:0/SM18:0 (b[SE] = – 1.11[`], p = 0.03) were associated with worse verbal memory performance over time. These associations were not mediated by whether or not patients had possible MVND at baseline.Conclusion:These findings support aberrant CerC18:0 metabolism as an early neurobiological change in vascular neurodegeneration. Future studies should measure enzymes responsible for conversion of sphingolipid precursors into CerC18:0 to assess enzymatic activity.

Role of Brain Derived Extracellular Vesicles in Decoding Sex Differences Associated with Nicotine Self-Administration

“…CERS2 is the primary synthase involved in synthesizing very long chain C24:1 ceramide through the de novo pathway, whereas NSMASE2 is primarily involved in the production of ceramide by hydrolysis of sphingomyelin. Elevated ceramide levels have been associated with poor cardiovascular health and memory impairment in older adults [65,66]. In our current study, the expression levels of CERS2 along with 4, 5, and 6 were significantly upregulated in the females after nicotine self-administration, while CERS3 was downregulated, albeit not significantly, which could suggest the vulnerability of females dependent on nicotine to faster aging.…”

New candidate blood biomarkers potentially associated with white matter hyperintensities progression

“…After reviewing the literature, MMP9, MET, and ASAH-2 were selected as biomarkers for the replication phase of the study, because these candidates have been previously connected to cerebrovascular or other neurological diseases 11 , 29 – 32 . In Fig.…”

Endostatin as a Mediator Between Endothelial Function and Cognitive Performance in Those at Risk for Vascular Cognitive Impairment

“…Future studies should utilize more domain-specific neuropsychological tests to investigate the mediation effect. Two appropriate tests might include Trails B for executive function and processing speed and the California Verbal Learning Test for delayed recall, both of which assess domains that might be affected in patients with mild VCI and CAD [13,26,27,[71][72][73][74].…”