Title | Ceramide Accumulation Is Associated with Declining Verbal Memory in Coronary Artery Disease Patients: An Observational Study. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Chan, P, Saleem, M, Herrmann, N, Mielke, MM, Haughey, NJ, Oh, PI, Kiss, A, Lanctôt, KL |
Journal | J Alzheimers Dis |
Volume | 64 |
Issue | 4 |
Pagination | 1235-1246 |
Date Published | 2018 |
ISSN | 1875-8908 |
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. |
DOI | 10.3233/JAD-180030 |
Alternate Journal | J. Alzheimers Dis. |
PubMed ID | 30010121 |
PubMed Central ID | PMC6087453 |
Grant List | R01 DA040390 / DA / NIDA NIH HHS / United States P30 MH075673 / MH / NIMH NIH HHS / United States R01 MH110246 / MH / NIMH NIH HHS / United States P50 AG044170 / AG / NIA NIH HHS / United States R01 AG049704 / AG / NIA NIH HHS / United States RF1 AG055151 / AG / NIA NIH HHS / United States F31 MH096630 / MH / NIMH NIH HHS / United States P01 MH105280 / MH / NIMH NIH HHS / United States |