Circulating ceramide ratios and risk of vascular brain aging and dementia

Ann Clin Transl Neurol. 2020 Feb;7(2):160-168. doi: 10.1002/acn3.50973. Epub 2020 Jan 16.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging / blood*
  • Alzheimer Disease / blood
  • Alzheimer Disease / epidemiology
  • Biomarkers / blood
  • Ceramides / blood*
  • Cross-Sectional Studies
  • Dementia / blood*
  • Dementia / epidemiology*
  • Female
  • Humans
  • Leukoaraiosis / blood*
  • Leukoaraiosis / diagnostic imaging
  • Leukoaraiosis / pathology
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Massachusetts / epidemiology
  • Middle Aged
  • Proportional Hazards Models


  • Biomarkers
  • Ceramides