Department of Neurology, Oregon Health and Science University, Portland, OR, USA.
Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA.
J Alzheimers Dis. 2020;74(1):65-77. doi: 10.3233/JAD-191197.
Cerebrovascular disease is a common cause of dementia in older adults, and potentially preventable with early intervention. Oxylipins are produced from the oxidation of long-chain polyunsaturated fatty acids (PUFA) possessing potent vascular effects. Oxylipins generated from the cytochrome P450 pathway are enzymatically converted to diols by soluble epoxide hydrolase (sEH); sEH products have been associated with small vessel ischemic disease. Little is known about oxylipins' impact on markers of dementia risk.
An exploratory examination of the association between omega-6 and omega-3 derived oxylipins, brain MRI, and cognition.
Thirty-seven non-demented participants with controlled hypertension (mean age 65.6 years) were enrolled in a dementia prevention study investigating fish oil and lipoic acid on preserving cognitive function. Baseline associations between plasma oxylipins, white matter hyperintensity (WMH), and Trails-B were examined using linear regression. P450-derived diol/epoxide ratio was an indirect measure of sEH activity.
Omega-6 derived 9-HODE was associated with increased WMH (p = 0.017) and reduced grey matter volume (p = 0.02). Omega-6 P450-derived diol/epoxide ratio 9,10-DiHOME/9,10-EpOME was associated with increased WMH (p = 0.035) and poorer performance on Trails-B (p = 0.05); ratio14,15-DHET/14,15-EET was associated with increased WMH (p = 0.045). Omega-3 P450-derived diol/epoxide ratio 19,20-DiHDPE/19,20-EpDPE was associated with increased WMH (p = 0.04) and poorer performance on Trails-B (p = 0.04). Arachidonic acid was associated with better performance on Trails-B (p = 0.012); Omega-3 derived 16,17-EpDPE was associated with decreased WMH (p = 0.005).
With the exception of arachidonic acid, it was specific oxylipin products, not their parent PUFAs, that were associated with unfavorable and favorable MRI and cognitive markers of dementia risk.
脑血管疾病是老年人痴呆的常见病因，通过早期干预有可能预防。氧化脂质是由长链多不饱和脂肪酸（PUFA）氧化产生的，具有很强的血管作用。细胞色素 P450 途径产生的氧化脂质被可溶性环氧化物水解酶（sEH）酶促转化为二醇；sEH 的产物与小血管缺血性疾病有关。关于氧化脂质对痴呆风险标志物的影响知之甚少。
探索研究ω-6 和 ω-3 衍生的氧化脂质与脑 MRI 和认知之间的关联。
37 名非痴呆、高血压得到控制的参与者（平均年龄 65.6 岁）被纳入一项痴呆预防研究，该研究调查了鱼油和硫辛酸对保持认知功能的作用。使用线性回归方法检验基线时血浆氧化脂质、脑白质高信号（WMH）和 Trails-B 之间的相关性。P450 衍生二醇/环氧化物比值是 sEH 活性的间接衡量指标。
ω-6 衍生的 9-HODE 与 WMH 增加相关（p=0.017）和灰质体积减少相关（p=0.02）。ω-6 P450 衍生二醇/环氧化物比值 9,10-DiHOME/9,10-EpOME 与 WMH 增加相关（p=0.035）和 Trails-B 表现较差相关（p=0.05）；比值 14,15-DHET/14,15-EET 与 WMH 增加相关（p=0.045）。ω-3 P450 衍生二醇/环氧化物比值 19,20-DiHDPE/19,20-EpDPE 与 WMH 增加相关（p=0.04）和 Trails-B 表现较差相关（p=0.04）。花生四烯酸与 Trails-B 表现较好相关（p=0.012）；ω-3 衍生的 16,17-EpDPE 与 WMH 减少相关（p=0.005）。
除了花生四烯酸外，与不利的和有利的 MRI 和痴呆风险认知标志物相关的是特定的氧化脂质产物，而不是它们的母体多不饱和脂肪酸。
