Higher Brain Perfusion May Not Support Memory Functions in Cognitively Normal Carriers of the ApoE ε4 Allele Compared to Non-Carriers.
Higher Brain Perfusion May Not Support Memory Functions in Cognitively Normal Carriers of the ApoE ε4 Allele Compared to Non-Carriers.
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DOI：
10.3389/fnagi.2016.00151
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发表时间：
2016
影响因子：
4.8
通讯作者：
Wierenga CE
中科院分区：
文献类型：
--
作者：
Zlatar ZZ;Bischoff-Grethe A;Hays CC;Liu TT;Meloy MJ;Rissman RA;Bondi MW;Wierenga CE
脑血流量（CBF）中的脑血管病相关变化（CBF）将必要的营养物质带到大脑中，与轻度认知障碍（MCI）和阿尔茨海默病（AD）的风险增加有关。CBF和认知之间的关联是否受载脂蛋白E（ApoE）ε4基因型（AD的一个已知风险因素）的调节，仍然没有得到充分研究，大多数研究集中在探索CBF中存在诊断组差异的大脑区域（即，认知正常对比MCI对比AD）。该研究通过动脉自旋标记（ASL）磁共振成像（MRI）和言语记忆功能，使用复合评分测量了59名认知正常的老年人（38 ε3; 21 ε4）的静息CBF。采用线性混合效应模型研究ApoE基因型是否改变了言语记忆成绩与静息脑血流量之间的体素关系。结果表明，ApoE ε4等位基因携带者的言语记忆功能与内侧额叶皮层、内侧和外侧颞叶皮层、顶叶区、小脑和基底节的CBF呈负相关。ε3基因携带者的言语记忆功能与内侧额叶皮层、丘脑、丘脑和基底节的CBF呈正相关。研究结果表明，较高的CBF与认知正常的ε4携带者的言语记忆功能较差相关，这可能反映了神经血管单位内的失调，这不再支持认知。结果进行了讨论的背景下，血管理论的AD风险。
Age-related changes in cerebral blood flow (CBF), which carries necessary nutrients to the brain, are associated with increased risk for mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Whether the association between CBF and cognition is moderated by apolipoprotein E (ApoE) ε4 genotype, a known risk factor for AD, remains understudied, with most research focusing on exploring brain regions in which there are diagnostic group differences in CBF (i.e., cognitively normal vs. MCI vs. AD). This study measured resting CBF via arterial spin labeling (ASL) magnetic resonance imaging (MRI) and verbal memory functions using a composite score in 59 older adults with normal cognition (38 ε3; 21 ε4). Linear mixed effect models were employed to investigate if the voxel-wise relationship between verbal memory performance and resting CBF was modified by ApoE genotype. Results indicated that carriers of the ApoE ε4 allele display negative associations between verbal memory functions and CBF in medial frontal cortex, medial and lateral temporal cortex, parietal regions, insula, and the basal ganglia. Contrarily, ε3 carriers exhibited positive associations between verbal memory functions and CBF in medial frontal cortex, thalamus, insula, and basal ganglia. Findings suggest that higher CBF was associated with worse verbal memory functions in cognitively normal ε4 carriers, perhaps reflecting dysregulation within the neurovascular unit, which is no longer supportive of cognition. Results are discussed within the context of the vascular theory of AD risk.