Coughlan Gillian, Larsen Ryan, Kim Min, White David, Gillings Rachel, Irvine Michael, Scholey Andrew, Cohen Neal, Legido-Quigley Cristina, Hornberger Michael, Minihane Anne-Marie
Norwich Medical School, University of East Anglia, Norwich, UK.
Rotman Research Institute, Baycrest, Toronto, ON, Canada.
Brain Commun. 2021 May 11;3(2):fcab085. doi: 10.1093/braincomms/fcab085. eCollection 2021.
Docosahexaenoic acid is the main long-chain omega-3 polyunsaturated fatty acids in the brain and accounts for 30-40% of fatty acids in the grey matter of the human cortex. Although the influence of docosahexaenoic acid on memory function is widely researched, its association with brain volumes is under investigated and its association with spatial navigation is virtually unknown. This is despite the fact that spatial navigation deficits are a new cognitive fingerprint for symptomatic and asymptomatic Alzheimer's disease. We investigated the cross-sectional relationship between docosahexaenoic acid levels and the major structural and cognitive markers of preclinical Alzheimer's disease, namely hippocampal volume, entorhinal volume and spatial navigation ability. Fifty-three cognitively normal adults underwent volumetric magnetic resonance imaging, measurements of serum docosahexaenoic acid (DHA, including lysophosphatidylcholine DHA) and ε4 genotyping. Relative regional brain volumes were calculated and linear regression models were fitted to examine DHA associations with brain volume. genotype modulated serum DHA associations with entorhinal cortex volume and hippocampal volume. Linear models showed that greater serum DHA was associated with increased entorhinal cortex volume, but not hippocampal volume, in non ε4 carriers. also interacted with serum lysophosphatidylcholine DHA to predict hippocampal volume. After testing interactions between DHA and on brain volume, we investigated whether DHA and interact to predict spatial navigation performance on a novel virtual reality diagnostic test for Alzheimer's disease in an independent population of genotyped adults ( = 46). genotype modulated DHA associations with spatial navigation performance, showing that DHA was inversely associated with path integration in ε4 carriers only. This exploratory analysis suggests that interventions aiming to increase DHA blood levels to protect against cognitive decline should consider ε4 carrier status. Future work should focus on replicating our initial findings and establishing whether a specific dose of supplementary DHA, at a particular time in the preclinical disease course can have a positive impact on Alzheimer's disease progression in ε4 carriers.
二十二碳六烯酸是大脑中主要的长链ω-3多不饱和脂肪酸，占人类大脑皮质灰质中脂肪酸的30%-40%。尽管二十二碳六烯酸对记忆功能的影响已得到广泛研究，但其与脑容量的关联仍在研究中，而其与空间导航的关联实际上尚不清楚。尽管空间导航缺陷是有症状和无症状阿尔茨海默病的一种新的认知特征，但情况依然如此。我们研究了二十二碳六烯酸水平与临床前阿尔茨海默病的主要结构和认知标志物之间的横断面关系，即海马体积、内嗅体积和空间导航能力。53名认知正常的成年人接受了容积磁共振成像、血清二十二碳六烯酸（DHA，包括溶血磷脂酰胆碱DHA）测量和ε4基因分型。计算相对区域脑容量，并拟合线性回归模型以检验DHA与脑容量的关联。基因型调节血清DHA与内嗅皮质体积和海马体积的关联。线性模型显示，在非ε4携带者中，较高的血清DHA与内嗅皮质体积增加相关，但与海马体积无关。 也与血清溶血磷脂酰胆碱DHA相互作用以预测海马体积。在测试DHA和 对脑容量的相互作用后，我们在一个独立的基因型成年人群体（n = 46）中研究了DHA和 是否相互作用以预测阿尔茨海默病新型虚拟现实诊断测试中的空间导航表现。基因型调节DHA与空间导航表现的关联，表明DHA仅与ε4携带者的路径整合呈负相关。这项探索性分析表明，旨在提高DHA血液水平以预防认知衰退的干预措施应考虑ε4携带者状态。未来的工作应集中在复制我们的初步发现，并确定在临床前疾病过程中的特定时间给予特定剂量的补充DHA是否会对ε4携带者的阿尔茨海默病进展产生积极影响。
