先前的研究已经显示了遗传性FTD中症状前皮质萎缩的证据。虽然初步调查还发现了早期深层灰质体积损失,对皮质下受累的程度知之甚少,特别是在次区域内,以及遗传群体之间的差异。
包括来自遗传FTD倡议(GENFI)的480个突变携带者(198个GRN,202C9orf72,80MAPT),与298名非携带者认知正常对照。在体积3TT1加权MRI扫描上使用自动分割方法生成感兴趣的皮质和皮质下体积。突变携带者根据其全球CDR®加NACCFTLD评分分为三个疾病阶段:无症状(0),可能或轻度症状(0.5)和完全症状(1或更多)。
在所有三组中,皮质下受累见于表型转换前的CDR0.5期,而在C9orf72和MAPT突变携带者中,在CDR0期也有参与.在C9orf72扩张载体中,最早的体积变化是在丘脑亚核(特别是髓核和外侧膝状,9-10%)小脑(小叶VIIa-CrusII和VIIIb,2-3%),海马(特别是前下颌和CA1,2-3%),杏仁核(所有亚区,2-6%)和下丘脑(上结节区,1%)。在MAPT突变携带者中,在海马的CDR0处看到了变化(下膜,前丘和尾巴,3-4%)和杏仁核(副基底和浅表核,2-4%)。GRN突变携带者在海马前膜的CDR0.5处显示出皮质下差异(8%)。
C9orf72扩张载体显示出最早和最广泛的变化,包括丘脑,基底神经节和内侧颞叶。通过调查各个子区域,在边缘系统内的MAPT突变携带者的CDR0也可以看到变化。我们的结果表明,即使在前驱症状发作之前,皮质下脑体积也可以用作神经变性的标志物。
Studies have previously shown evidence for presymptomatic cortical atrophy in genetic FTD. Whilst initial investigations have also identified early deep grey matter volume loss, little is known about the extent of subcortical involvement, particularly within subregions, and how this differs between genetic groups.
480 mutation carriers from the Genetic FTD Initiative (GENFI) were included (198 GRN, 202 C9orf72, 80 MAPT), together with 298 non-carrier cognitively normal controls. Cortical and subcortical volumes of interest were generated using automated parcellation methods on volumetric 3 T T1-weighted MRI scans. Mutation carriers were divided into three disease stages based on their global CDR® plus NACC FTLD score: asymptomatic (0), possibly or mildly symptomatic (0.5) and fully symptomatic (1 or more).
In all three groups, subcortical involvement was seen at the CDR 0.5 stage prior to phenoconversion, whereas in the C9orf72 and MAPT mutation carriers there was also involvement at the CDR 0 stage. In the C9orf72 expansion carriers the earliest volume changes were in thalamic subnuclei (particularly pulvinar and lateral geniculate, 9-10%) cerebellum (lobules VIIa-Crus II and VIIIb, 2-3%), hippocampus (particularly presubiculum and CA1, 2-3%), amygdala (all subregions, 2-6%) and hypothalamus (superior tuberal region, 1%). In MAPT mutation carriers changes were seen at CDR 0 in the hippocampus (subiculum, presubiculum and tail, 3-4%) and amygdala (accessory basal and superficial nuclei, 2-4%). GRN mutation carriers showed subcortical differences at CDR 0.5 in the presubiculum of the hippocampus (8%).
C9orf72 expansion carriers show the earliest and most widespread changes including the thalamus, basal ganglia and medial temporal lobe. By investigating individual subregions, changes can also be seen at CDR 0 in MAPT mutation carriers within the limbic system. Our results suggest that subcortical brain volumes may be used as markers of neurodegeneration even prior to the onset of prodromal symptoms.