Circulating ceramide ratios and risk of vascular brain aging and dementia

Emer R. McGrath, Jayandra J. Himali, Vanessa Xanthakis, Meredith S. Duncan, Jean E. Schaffer, Daniel S. Ory, Linda R. Peterson, Charles DeCarli, Matthew P. Pase, Claudia L. Satizabal, Ramachandran S. Vasan, Alexa S. Beiser, Sudha Seshadri

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Background: We determined the association between ratios of plasma ceramide species of differing fatty-acyl chain lengths and incident dementia and Alzheimer’s disease (AD) dementia in a large, community-based sample. Methods: We measured plasma ceramide levels in 1892 [54% women, mean age 70.1 (SD 6.9) yr.] dementia-free Framingham Offspring Study cohort participants between 2005 and 2008. We related ratios of very long-chain (C24:0, C22:0) to long-chain (C16:0) ceramides to subsequent risk of incident dementia and AD dementia. Structural MRI brain measures were included as secondary outcomes. Results: During a median 6.5 year follow-up, 81 participants developed dementia, of whom 60 were diagnosed with AD dementia. In multivariable Cox-proportional hazards analyses, each standard deviation (SD) increment in the ratio of ceramides C24:0/C16:0 was associated with a 27% reduction in the risk of dementia (HR 0.73, 95% CI 0.56–0.96) and AD dementia (HR 0.73, 95% CI 0.53–1.00). The ratio of ceramides C22:0/C16:0 was also inversely associated with incident dementia (HR per SD 0.75, 95% CI 0.57–0.98), and approached statistical significance for AD (HR 0.73, 95% CI 0.53–1.01, P = 0.056). Higher ratios of ceramides C24:0/C16:0 and C22:0/C16:0 were also cross-sectionally associated with lower white matter hyperintensity burden on MRI (−0.05 ± 0.02, P = 0.02; −0.06 ± 0.02, P = 0.003; respectively per SD increase), but not with other MRI brain measures. Conclusions: Higher plasma ratios of very long-chain to long-chain ceramides are associated with a reduced risk of incident dementia and AD dementia in our community-based sample. Circulating ceramide ratios may serve as potential biomarkers for predicting dementia risk in cognitively healthy adults.

Original languageEnglish
Pages (from-to)160-168
Number of pages9
JournalAnnals of Clinical and Translational Neurology
Issue number2
StatePublished - Feb 1 2020

Bibliographical note

Funding Information:
The Framingham Heart Study is supported by the National Heart, Lung, and Blood Institute (contract no. N01-HC-25195, no. HHSN268201500001I and no. 75N92019D00031) and this research is supported by the Alzheimer’s Association Clinician Scientist Fellowship (AACSF-18-566570), NHLBI grants R01 HL60040, R01 HL70100 and P20 HL113444, grants from the National Institute on Aging (R01 AG054076, R01 AG049607, R01 AG033193, U01 AG049505, U01 AG052409) and the National Institute of Neurological Disorders and Stroke (NS017950 and UH2 NS100605). MPP is funded by a National Heart Foundation of Australia Future Leader. None of the funding entities had any role in the design and conduct of the study; collection, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. The views and opinions offered in this manuscript are those of the authors and are not necessarily those of the funding agencies.

Publisher Copyright:
© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.

ASJC Scopus subject areas

  • Neuroscience (all)
  • Clinical Neurology


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