The Heart-Mind Connection: Evaluating the Association Between Ceramides and Cognitive Decline in Coronary Artery Disease
Condition: Coronary Artery Disease
MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Cognitive Dysfunction
Study type: Observational

Summary: 
      Many studies have shown that those with coronary artery disease (CAD) have a more rapid
      decline in memory than expected and that they are at an increased risk of developing
      dementia. It is not understood how memory decline is linked to CAD; however, it has recently
      been discovered that certain byproducts of fat breakdown involved in the development of CAD,
      called ceramides, can harm brain cells. In the present study the investigators will recruit
      129 CAD patients from a cardiac rehabilitation facility and measure memory performance and
      blood ceramide concentrations at baseline, 3 months and 6 months. The investigators will also
      measure important blood messengers of inflammation and assess whether they are associated
      with ceramide production. In addition, relationships between ceramides and other aspects of
      brain function, such as thinking speed and the ability to plan and sort information will be
      explored.
    

Detailed description: 
      Coronary artery disease (CAD) affects about 19.8% of Canadians over the age of 65 and
      significantly affects quality of life. Of particular importance, cognitive impairment,
      ranging from cognitive complaints to vascular dementia, is frequently part of the clinical
      presentation of CAD. Our own prospective pilot data suggest that 22.5% of CAD patients
      attending cardiac rehabilitation (CR) have evidence of cognitive impairment with lower verbal
      memory performance, a marker of hippocampal function, predicting poorer CR outcomes. The
      pathophysiological mechanisms that may contribute to cognitive decline in those with CAD have
      not been fully elucidated.

      Ceramides are metabolites of sphingomyelin, lipid species enriched in the outer leaflet of
      the plasma membrane and cell organelles of all tissues. Higher peripheral blood
      concentrations of ceramides have been associated with the development and progression of CAD.
      We propose to use a specific and sensitive electrospray ionization-tandem mass spectrometry
      (ESI-MS/MS) assay to measure concentrations of ceramide species from human plasma and
      elucidate the relationship between ceramides and the change in verbal memory performance over
      6 months in 129 subjects with CAD undergoing CR.

      We hypothesize that higher plasma concentrations of the long chain ceramide species C22:0 and
      C24:0 will be associated with decline in verbal memory performance and overall cognitive
      performance as assessed by a standardized battery of cognitive tests recommended for the
      investigation of vascular cognitive impairment. We also hypothesize that changes in the
      plasma concentration of TNF-α (tumor necrosis factor-alpha) will be associated with changes
      in plasma concentrations of C22:0 and C24:0 over 6 months.

      This study aims to clarify the significance of a novel mechanism involving ceramides and the
      propagation of inflammatory signals from the periphery to the brain in mediating
      neurodegeneration associated with CAD.
    

Intervention name(s): Exercise
Intervention type(s): Behavioral
Intervention description(s): All individuals will be prescribed an exercise regimen according to their cardiac rehabilitation program
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Patients with coronary artery disease participating in a cardiac rehabilitation exercise
        program
      
Biospecimen description: 
      Whole blood for ApoE4 genotyping
    
Keywords: Ceramides; Lipids