White matter microstructure in late middle-age: Effects of apolipoprotein E4 and parental family history of Alzheimer's disease
White matter microstructure in late middle-age: Effects of apolipoprotein E4 and parental family history of Alzheimer's disease
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DOI：
10.1016/j.nicl.2014.04.008
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发表时间：
2014-01-01
影响因子：
4.2
通讯作者：
Bendlin, Barbara B.
中科院分区：
文献类型：
--
作者：
Adluru, Nagesh;Destiche, Daniel J.;Bendlin, Barbara B.
简介：关于阿尔茨海默病（AD）危险因素对认知健康成年人白色物质微结构的影响仍然知之甚少。这项横断面研究的目的是评估两个众所周知的AD危险因素，父母家族史和APOE 4基因型的影响。方法：本研究包括343名来自威斯康星州阿尔茨海默病预防登记处的参与者，他们接受了弥散张量成像（DTI）。感兴趣的区域进行分析的分数各向异性地图，除了平均值，径向和轴向扩散率地图，对齐到一个共同的模板空间，使用一个同构的，基于张量的配准方法。分析集中于已知在AD中受影响的脑区域，包括胼胝体、上级纵束、穹窿、扣带和钩束。分析评估了APOE 4、父母AD家族史、年龄和性别对中年晚期参与者（年龄47-76岁）白色微结构的影响。结果：APOE 4和父母AD家族史均与微结构白色物质差异相关。父母有AD家族史的参与者在胼胝体和上级纵束的前部有较高的FA。我们观察到家族史和APOE 4之间的相互作用，其中家族史阳性但APOE 4阴性的参与者钩束的轴向扩散率较低，家族史阳性和APOE 4阳性的参与者在该区域的轴向扩散率较高。我们还观察到APOE 4和年龄之间的相互作用，其中APOE 4携带者的老年参与者（>= 65岁）与非携带者相比，在上级纵束和邻近扣带皮质的扣带束部分具有更高的MD。与非携带者相比，APOE 4携带者的老年参与者也表现出更高的径向扩散率。在所有参与者中，年龄对FA、MD以及轴向和径向扩散率有影响。结论：APOE 4基因型、父母AD家族史、年龄和性别均与中晚期成年人的微结构白色物质差异有关。在有AD风险的参与者中，扩散特征的改变-预期和意外-可能代表在疾病的最早阶段发生的细胞变化，但需要进一步的工作。在更有可能经历后期临床前病理学的参与者中观察到更高的平均、径向和轴向扩散率，包括年龄较大且携带APOE 4的参与者，或APOE 4和父母AD家族史均为阳性的参与者。(C)2014作者爱思唯尔公司出版
Introduction: Little is still known about the effects of risk factors for Alzheimer's disease (AD) on white matter microstructure in cognitively healthy adults. The purpose of this cross-sectional study was to assess the effect of two well-known risk factors for AD, parental family history and APOE4 genotype. Methods: This study included 343 participants from the Wisconsin Registry for Alzheimer's Prevention, who underwent diffusion tensor imaging (DTI). A region of interest analysis was performed on fractional anisotropy maps, in addition to mean, radial, and axial diffusivity maps, aligned to a common template space using a diffeomorphic, tensor-based registration method. The analysis focused on brain regions known to be affected in AD including the corpus callosum, superior longitudinal fasciculus, fornix, cingulum, and uncinate fasciculus. Analyses assessed the impact of APOE4, parental family history of AD, age, and sex on white matter microstructure in late middle-aged participants (aged 47-76 years).Results: Both APOE4 and parental family history were associated with microstructural white matter differences. Participants with parental family history of AD had higher FA in the genu of the corpus callosum and the superior longitudinal fasciculus. We observed an interaction between family history and APOE4, where participants who were family history positive but APOE4 negative had lower axial diffusivity in the uncinate fasciculus, and participants who were both family history positive and APOE4 positive had higher axial diffusivity in this region. We also observed an interaction between APOE4 and age, whereby older participants (>= 65 years of age) who were APOE4 carriers, had higher MD in the superior longitudinal fasciculus and in the portion of the cingulum bundle running adjacent to the cingulate cortex, compared to non-carriers. Older participants who were APOE4 carriers also showed higher radial diffusivity in the genu compared to non-carriers. Across all participants, age had an effect on FA, MD, and axial and radial diffusivities. Sex differences were observed in FA and radial diffusivity.Conclusion: APOE4 genotype, parental family history of AD, age, and sex are all associated with microstructural white matter differences in late middle-aged adults. In participants at risk for AD, alterations in diffusion characteristics-both expected and unexpected-may represent cellular changes occurring at the earliest disease stages, but further work is needed. Higher mean, radial, and axial diffusivities were observed in participants who are more likely to be experiencing later stage preclinical pathology, including participants who were both older and carried APOE4, or who were positive for both APOE4 and parental family history of AD. (C) 2014 The Authors. Published by Elsevier Inc.