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

Parco Chan, Mahwesh Saleem, Nathan Herrmann, Michelle M Mielke, Norman J. Haughey, Paul I. Oh, Alexander Kiss, Krista L. Lanctôt

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1235-1246
Number of pages12
JournalJournal of Alzheimer's disease : JAD
Volume64
Issue number4
DOIs
StatePublished - Jan 1 2018

Fingerprint

Ceramides
Observational Studies
Coronary Artery Disease
Blood Vessels
Sphingomyelins
Verbal Learning
Sphingolipids
Vulnerable Populations
Disease Progression
Body Mass Index
Biomarkers
Education

Keywords

  • Ceramides
  • cognition
  • coronary artery disease
  • memory
  • sphingolipids

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

Ceramide Accumulation Is Associated with Declining Verbal Memory in Coronary Artery Disease Patients : An Observational Study. / Chan, Parco; Saleem, Mahwesh; Herrmann, Nathan; Mielke, Michelle M; Haughey, Norman J.; Oh, Paul I.; Kiss, Alexander; Lanctôt, Krista L.

In: Journal of Alzheimer's disease : JAD, Vol. 64, No. 4, 01.01.2018, p. 1235-1246.

Research output: Contribution to journalArticle

Chan, Parco ; Saleem, Mahwesh ; Herrmann, Nathan ; Mielke, Michelle M ; Haughey, Norman J. ; Oh, Paul I. ; Kiss, Alexander ; Lanctôt, Krista L. / Ceramide Accumulation Is Associated with Declining Verbal Memory in Coronary Artery Disease Patients : An Observational Study. In: Journal of Alzheimer's disease : JAD. 2018 ; Vol. 64, No. 4. pp. 1235-1246.
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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.",
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T1 - Ceramide Accumulation Is Associated with Declining Verbal Memory in Coronary Artery Disease Patients

T2 - An Observational Study

AU - Chan, Parco

AU - Saleem, Mahwesh

AU - Herrmann, Nathan

AU - Mielke, Michelle M

AU - Haughey, Norman J.

AU - Oh, Paul I.

AU - Kiss, Alexander

AU - Lanctôt, Krista L.

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N2 - 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.

AB - 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.

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KW - sphingolipids

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