METHODS: We measured 14 sphingolipid species in plasma samples from 4488 participants (mean age 76.2 years; 40% male; and 25% apolipoprotein E (APOE) ε4 allele carriers). Cognitive decline was assessed annually across 6 years using modified Mini-Mental State Examination (3MSE) and Digital Symbol Substitution Test (DSST). Additionally, a subset of 3050 participants were followed for clinically adjudicated dementia.
RESULTS: Higher plasma levels of sphingomyelin-d18:1/16:0 (SM-16) were associated with a faster cognitive decline measured with 3MSE, in contrast, higher levels of sphingomyelin-d18:1/22:0 (SM-22) were associated with slower decline in cognition measured with DSST. In Cox regression, higher levels of SM-16 (hazard ration [HR] = 1.24 [95% confidence interval [CI]: 1.08-1.44]) and ceramide-d18:1/16:0 (Cer-16) (HR = 1.26 [95% CI: 1.10-1.45]) were associated with higher risk of incident dementia.
CONCLUSIONS: Several sphingolipid species appear to be involved in cognitive decline and dementia risk.
UNASSIGNED: Plasma levels of sphingolipids were associated with cognitive decline and dementia risk.Ceramides and sphingomyelins with palmitic acid were associated with faster annual cognitive decline and increased risk of dementia.The direction of association depended on the covalently bound saturated fatty acid chain length in analysis of cognitive decline.
方法:我们测量了4488名参与者的血浆样本中的14种鞘脂类(平均年龄76.2岁;40%为男性;25%载脂蛋白E(APOE)ε4等位基因携带者)。使用改良的迷你精神状态检查(3MSE)和数字符号替代测试(DSST),每年评估6年的认知下降。此外,对3050名参与者中的一部分进行了临床判定性痴呆的随访.
结果:较高的血浆鞘磷脂-d18:1/16:0(SM-16)水平与3MSE测量的更快的认知下降有关,相比之下,较高水平的鞘磷脂-d18:1/22:0(SM-22)与DSST测量的认知下降较慢相关.在Cox回归中,较高的SM-16水平(危险比[HR]=1.24[95%置信区间[CI]:1.08~1.44])和神经酰胺-d18:1/16:0(Cer-16)水平(HR=1.26[95%CI:1.10~1.45])与较高的痴呆发生率相关.
结论:几种鞘脂类似乎与认知衰退和痴呆风险有关。
■血浆鞘脂水平与认知功能下降和痴呆风险相关。神经酰胺和鞘磷脂与棕榈酸与较快的年度认知功能下降和痴呆风险增加有关。在认知衰退的分析中,缔合的方向取决于共价结合的饱和脂肪酸链长度。