Circulating ceramide ratios and risk of vascular brain aging and dementia
Abstract 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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-02-01
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| Series: | Annals of Clinical and Translational Neurology |
| Online Access: | https://doi.org/10.1002/acn3.50973 |
| _version_ | 1818948132997693440 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Emer R. McGrath |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-20T08:41:57Z |
| format | Article |
| id | doaj.art-0ee89036409f4d04b80fe977f60bc8ca |
| institution | Directory Open Access Journal |
| issn | 2328-9503 |
| language | English |
| last_indexed | 2024-12-20T08:41:57Z |
| publishDate | 2020-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Annals of Clinical and Translational Neurology |
| spelling | doaj.art-0ee89036409f4d04b80fe977f60bc8ca2022-12-21T19:46:22ZengWileyAnnals of Clinical and Translational Neurology2328-95032020-02-017216016810.1002/acn3.50973Circulating ceramide ratios and risk of vascular brain aging and dementiaEmer R. McGrath0Jayandra J. Himali1Vanessa Xanthakis2Meredith S. Duncan3Jean E. Schaffer4Daniel S. Ory5Linda R. Peterson6Charles DeCarli7Matthew P. Pase8Claudia L. Satizabal9Ramachandran S. Vasan10Alexa S. Beiser11Sudha Seshadri12Department of Neurology Brigham & Women’s Hospital Boston MassachusettsFramingham Heart Study Framingham MassachusettsFramingham Heart Study Framingham MassachusettsVanderbilt University Medical Center Nashville TennesseeWashington University School of Medicine St Louis MissouriWashington University School of Medicine St Louis MissouriWashington University School of Medicine St Louis MissouriDepartment of Neurology University of California Davis CaliforniaFramingham Heart Study Framingham MassachusettsFramingham Heart Study Framingham MassachusettsFramingham Heart Study Framingham MassachusettsFramingham Heart Study Framingham MassachusettsFramingham Heart Study Framingham MassachusettsAbstract 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.https://doi.org/10.1002/acn3.50973 |
| spellingShingle | 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 Circulating ceramide ratios and risk of vascular brain aging and dementia Annals of Clinical and Translational Neurology |
| title | Circulating ceramide ratios and risk of vascular brain aging and dementia |
| title_full | Circulating ceramide ratios and risk of vascular brain aging and dementia |
| title_fullStr | Circulating ceramide ratios and risk of vascular brain aging and dementia |
| title_full_unstemmed | Circulating ceramide ratios and risk of vascular brain aging and dementia |
| title_short | Circulating ceramide ratios and risk of vascular brain aging and dementia |
| title_sort | circulating ceramide ratios and risk of vascular brain aging and dementia |
| url | https://doi.org/10.1002/acn3.50973 |
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