Radiology:DTI有助于识别具有早发性AD遗传风险者大脑结构变化

2021-11-12 自由影像之光 MedSci原创

常染色体显性阿尔茨海默病突变携带者的白质结构连接低于非携带者低,并与估计的发病时间相关。

阿尔茨海默病(AD)的病理证据可在临床症状出现前数年检测到。基于成像技术识别具有早发性AD遗传风险的人的大脑结构变化,可能为基因如何影响导致痴呆的病理级联提供深入见解。

Jeffrey W. Prescott等在Radiology杂志发表研究文章,评估认知正常常染色体显性阿尔茨海默病(ADAD)突变携带者与非携带者之间皮质网络结构连接的差异,并确定结构连接和皮质淀粉样蛋白负荷与估计痴呆发病年限(EYO)的横断面关系。

在这项前瞻性试验的探索性分析中,所有在2009年1月至2014年7月期间纳入显性遗传阿尔茨海默氏网络的参与者在基线认知正常。分析了T1加权MRI和弥散张量成像(DTI)图像。使用匹兹堡化合物B淀粉样PET成像分析突变载体。

大脑皮层分成三个皮层网络:默认网络、额顶叶控制网络和腹侧注意网络。利用DTI计算了三个网络的结构连通性。

采用一般线性模型检验突变携带者和非携带者之间的结构连通性的差异,以及突变携带者的结构连接、淀粉样蛋白负担和EYO之间的关系。通过相关网络分析来识别相关的临床和影像学标志物。

该研究共纳入30例突变携带者(平均年龄标准差34岁10岁;17名女性)和38名非携带者(平均年龄37岁10岁;20妇女)。与非携带者相比,突变携带者的前额顶叶控制网络结构连接较低(估计突变阳性效应,0.0266;P = 0.04)。

散点图显示了认知正常突变阳性参与者的额-顶叶控制网络整体效率与估计发病时间(EYO)(上)和匹兹堡化合物B淀粉样蛋白PET标准化摄取值比率(SUVr)(下)的对比。

非携带者(上)和突变携带者(下)的相关网络。基线临床和生物标志物描述符用圆圈表示。圆形阴影橙色表示淀粉样蛋白PET标准摄取值比率,黄色表示结构连接测量,绿色表示认知测量,紫色表示年龄,蓝色表示教育程度(Educ),红色表示估计到症状发作的年数(EYO)。认知测量包括即时词回忆(word Imm)、延迟词回忆(word Del)、即时逻辑记忆(Logic Mem)和延迟逻辑记忆(Mem Units)。

在突变携带者中,EYO与额顶叶控制网络中的白质结构连接存在相关性(EYO估计效应,0.0015,P = 0.01)。突变携带者的皮质整体淀粉样蛋白负荷与EYO无显著相关性(P>0.05)。

该研究表明突变状态与低额-顶叶控制网络连接之间的关系。此外,当突变携带者接近常染色体显性阿尔茨海默病症状的预期发病年龄时,他们的额顶叶控制网络变化恶化。这些发现似乎与淀粉样蛋白负荷线性相关,尽管它们出现在淀粉样蛋白升高的背景下。未来对纵向临床MRI连通性数据和分子病理学PET标记物的研究可能有助于进一步阐明白质结构连通性在认知衰退中的作用,并将其作为阿尔茨海默病遗传风险患者的潜在生物标记物。

原文出处

Diffusion Tensor MRI Structural Connectivity and PET Amyloid Burden in Preclinical Autosomal Dominant Alzheimer Disease: The DIAN Cohort. Published Online:Oct 12 2021https://doi.org/10.1148/radiol.2021210383

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    2022-06-15 whlxd
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    2021-11-13 wmr116

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