Brain Institute, Department of Neurology, Oregon Health and Science University Portland, OR, USA.
Beckman Institute for Advanced Science and Technology Urbana, IL, USA.
Front Aging Neurosci. 2013 Dec 16;5:92. doi: 10.3389/fnagi.2013.00092. eCollection 2013.
Cross-sectional studies have identified long chain omega-3 polyunsaturated fatty acids (eicosapentaenoic acid 20:5n-3 and docosahexaenoic acid 22:6n-3 (O3PUFA) in association with fewer white matter lesions and better executive function in older adults. We hypothesized that O3PUFA are associated with less executive decline over time and that total white matter hyperintensity volume (WMH) mediates this association.
Eighty-six non-demented older adults were followed over 4 years after measurement of plasma O3PUFA with annual evaluations of cognitive function. A subset of these participants also had brain MRI of total WMH available to conduct a formal mediation analysis of a putative relationship between O3PUFA and cognitive function.
Mean age at baseline was 86, 62% were female and 11% carried the APOE4 allele. Each 100 μg/ml increase in plasma O3PUFA associated with 4 s less change in executive decline per year of aging (p = 0.02, fully adjusted model). O3PUFA was not associated with verbal memory or global cognitive changes. The significance of the association between O3PUFA and better executive function was lost once WMH was added to the regression model.
Executive decline with age appears to be a cognitive domain particularly sensitive to plasma O3PUFA in longitudinal examination. O3PUFA may modulate executive functioning by mechanisms underlying the development of WMH, a biologically plausible hypothesis that warrants further investigation.
横断面研究已经确定长链欧米伽-3 多不饱和脂肪酸（二十碳五烯酸 20:5n-3 和二十二碳六烯酸 22:6n-3（O3PUFA）与老年人较少的白质病变和更好的执行功能有关。我们假设 O3PUFA 与随时间推移的执行功能下降较少有关，并且总白质高信号体积（WMH）介导这种关联。
在测量血浆 O3PUFA 后，86 名非痴呆的老年人在 4 年内接受了年度认知功能评估。这些参与者中的一部分还进行了总 WMH 的脑部 MRI，以对 O3PUFA 和认知功能之间的假定关系进行正式的中介分析。
基线时的平均年龄为 86 岁，62%为女性，11%携带 APOE4 等位基因。血浆 O3PUFA 每增加 100μg/ml，与每年衰老时执行功能下降 4 秒相关（p=0.02，完全调整模型）。O3PUFA 与言语记忆或整体认知变化无关。一旦将 WMH 添加到回归模型中，O3PUFA 与更好的执行功能之间的关联就失去了意义。
随着年龄的增长，执行功能的下降似乎是一个认知领域，在纵向检查中特别容易受到血浆 O3PUFA 的影响。O3PUFA 可能通过WMH 发展的机制来调节执行功能，这是一个有生物学意义的假设，值得进一步研究。
