ω-6 和 ω-3 长链脂肪酸的氧化产物与认知正常的高血压老年人群的脑白质高信号体积增加和执行功能下降有关。
Oxidized Products of Omega-6 and Omega-3 Long Chain Fatty Acids Are Associated with Increased White Matter Hyperintensity and Poorer Executive Function Performance in a Cohort of Cognitively Normal Hypertensive Older Adults.
机构信息
Department of Neurology, Oregon Health and Science University, Portland, OR, USA.
Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA.
出版信息
J Alzheimers Dis. 2020;74(1):65-77. doi: 10.3233/JAD-191197.
BACKGROUND
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.
OBJECTIVE
An exploratory examination of the association between omega-6 and omega-3 derived oxylipins, brain MRI, and cognition.
METHODS
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.
RESULTS
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).
CONCLUSIONS
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.
背景
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。
目的
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。
方法
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。
结果
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）。
结论
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。
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