Serum ceramides increase the risk of Alzheimer disease The Women's Health and Aging Study II
Serum ceramides increase the risk of Alzheimer disease The Women's Health and Aging Study II
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DOI：
10.1212/wnl.0b013e318264e380
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发表时间：
2012-08-01
期刊：
影响因子：
9.9
通讯作者：
Carlson, Michelle C.
中科院分区：
文献类型：
--
作者：
Mielke, Michelle M.;Bandaru, Veera Vankata Ratnam;Carlson, Michelle C.
目的：先前的研究表明，高血清神经酰胺与记忆障碍和海马体积减少有关，但尚未将痴呆作为结果进行研究。本研究的目的是检查血清神经酰胺和鞘磷脂 (SM) 是否与全因痴呆和阿尔茨海默病 (AD) 风险增加相关。方法：参与者包括 99 名 70-79 岁、无痴呆、基线血清 SM 和神经酰胺水平的女性，参加一项基于人群的纵向研究，并在 9 年内随访最多 6 次。使用离散时间 Cox 比例生存分析检查以三分位数表示的基线脂质与全因痴呆和 AD 的关系。使用电喷雾电离串联质谱法对脂质进行分析。结果：99 名女性中有 27 名 (27.3%) 罹患痴呆症。其中，18 人（66.7%）被诊断出可能患有 AD。较高的基线血清神经酰胺（而非 SM）与 AD 风险增加相关；这些关系比全因痴呆症更强。与最低三分位数相比，神经酰胺 d18:1-C16:0 的中间和最高三分位数分别与 AD 风险增加 10 倍（95% 置信区间 [CI] 1.2-85.1）和 7.6 倍（95% CI 0.9-62.1）相关。神经酰胺 d18:1-C24:0（风险比 [HR] = 5.1，95% CI 1.1-23.6）和乳糖神经酰胺（HR = 9.8，95% CI 1.2-80.1）的最高三分位数也与 AD 风险相关。总胆固醇和高密度脂蛋白胆固醇以及甘油三酯与痴呆或 AD 无关。结论：这项初步研究的结果表明，特定种类的血清神经酰胺与 AD 相关，需要在更大规模的研究中继续进行检查。神经病学（R）2012；79：633-641
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. Neurology (R) 2012;79:633-641