TY - JOUR
T1 - Serum ceramides increase the risk of Alzheimer disease
T2 - The Women's Health and Aging Study II
AU - Mielke, Michelle M.
AU - Bandaru, Veera Vankata Ratnam
AU - Haughey, Norman J.
AU - Xia, Jin
AU - Fried, Linda P.
AU - Yasar, Sevil
AU - Albert, Marilyn
AU - Varma, Vijay
AU - Harris, Greg
AU - Schneider, Eric B.
AU - Rabins, Peter V.
AU - Bandeen-Roche, Karen
AU - Lyketsos, Constantine G.
AU - Carlson, Michelle C.
N1 - Funding Information:
M. Mielke, V.V.R. Bandaru, N. Haughey, J. Xia, L. Fried, S. Yasar, M. Albert, V. Varma, G. Harris, E. Schneider, P. Rabins, and K. Bandeen-Roche report no disclosures. C. Lyketsos has received grant support (research or CME) from the following organizations: NIMH, NIA, Associated Jewish Federation of Baltimore, Weinberg Foundation, Forest, GlaxoSmithKline, Eisai, Pfizer, Astra-Zeneca, Lilly, Ortho-McNeil, Bristol-Myers, and Novartis. Dr. Lyketsos has served as a consultant/advisor for Astra-Zeneca, GlaxoSmithKline, Eisai, Novartis, Forest, Supernus, Adlyfe, Takeda, Wyeth, Lundbeck, Merz, Lilly, and Genentech. Dr. Lyketsos has received honorarium or travel support from Pfizer, Forest, GlaxoSmithKline, and Health Monitor. M. Carlson reports no disclosures. Go to Neurology.org for full disclosures.
PY - 2012/8/14
Y1 - 2012/8/14
N2 - Objectives: Previous studies have shown that high serum ceramides are associated with memory impairment and hippocampal volume loss, but have not examined dementia as an outcome. The aim of this study was to examine whether serum ceramides and sphingomyelins (SM) were associated with an increased risk of all-cause dementia and Alzheimer disease (AD). Methods: Participants included 99 women without dementia aged 70-79, with baseline serum SM and ceramides, enrolled in a longitudinal population-based study and followed for up to 6 visits over 9 years. Baseline lipids, in tertiles, were examined in relation to all-cause dementia and AD using discrete time Cox proportional survival analysis. Lipids were analyzed using electrospray ionization tandem mass spectrometry. Results: Twenty-seven (27.3%) of the 99 women developed incident dementia. Of these, 18 (66.7%) were diagnosed with probable AD. Higher baseline serum ceramides, but not SM, were associated with an increased risk of AD; these relationships were stronger than with all-cause dementia. Compared to the lowest tertile, the middle and highest tertiles of ceramide d18:1-C16:0 were associated with a 10-fold (95% confidence interval [CI] 1.2-85.1) and 7.6-fold increased risk of AD (95% CI 0.9-62.1), respectively. The highest tertiles of ceramide d18:1-C24:0 (hazard ratio [HR] = 5.1, 95% CI 1.1-23.6) and lactosylceramide (HR = 9.8, 95% CI 1.2-80.1) were also associated with risk of AD. Total and high-density lipoprotein cholesterol and triglycerides were not associated with dementia or AD. Conclusions: Results from this preliminary study suggest that particular species of serum ceramides are associated with incident AD and warrant continued examination in larger studies.
AB - Objectives: Previous studies have shown that high serum ceramides are associated with memory impairment and hippocampal volume loss, but have not examined dementia as an outcome. The aim of this study was to examine whether serum ceramides and sphingomyelins (SM) were associated with an increased risk of all-cause dementia and Alzheimer disease (AD). Methods: Participants included 99 women without dementia aged 70-79, with baseline serum SM and ceramides, enrolled in a longitudinal population-based study and followed for up to 6 visits over 9 years. Baseline lipids, in tertiles, were examined in relation to all-cause dementia and AD using discrete time Cox proportional survival analysis. Lipids were analyzed using electrospray ionization tandem mass spectrometry. Results: Twenty-seven (27.3%) of the 99 women developed incident dementia. Of these, 18 (66.7%) were diagnosed with probable AD. Higher baseline serum ceramides, but not SM, were associated with an increased risk of AD; these relationships were stronger than with all-cause dementia. Compared to the lowest tertile, the middle and highest tertiles of ceramide d18:1-C16:0 were associated with a 10-fold (95% confidence interval [CI] 1.2-85.1) and 7.6-fold increased risk of AD (95% CI 0.9-62.1), respectively. The highest tertiles of ceramide d18:1-C24:0 (hazard ratio [HR] = 5.1, 95% CI 1.1-23.6) and lactosylceramide (HR = 9.8, 95% CI 1.2-80.1) were also associated with risk of AD. Total and high-density lipoprotein cholesterol and triglycerides were not associated with dementia or AD. Conclusions: Results from this preliminary study suggest that particular species of serum ceramides are associated with incident AD and warrant continued examination in larger studies.
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UR - http://www.scopus.com/inward/citedby.url?scp=84866077130&partnerID=8YFLogxK
U2 - 10.1212/WNL.0b013e318264e380
DO - 10.1212/WNL.0b013e318264e380
M3 - Article
C2 - 22815558
AN - SCOPUS:84866077130
SN - 0028-3878
VL - 79
SP - 633
EP - 641
JO - Neurology
JF - Neurology
IS - 7
ER -