BACKGROUND Frontotemporal dementia (FTD) and Alzheimer's disease (AD) are associated with divergent differences in grey matter volume, white matter diffusion, and functional connectivity. However, it is unknown at what disease stage these differences emerge. Here, we investigate whether divergent differences in grey matter volume, white matter diffusion, and functional connectivity are already apparent between cognitively healthy carriers of pathogenic FTD mutations, and cognitively healthy carriers at increased AD risk. METHODS We acquired multimodal magnetic resonance imaging (MRI) brain scans in cognitively healthy subjects with (n=39) and without (n=36) microtubule-associated protein Tau (MAPT) or progranulin (GRN) mutations, and with (n=37) and without (n=38) apolipoprotein E ε4 (APOE4) allele. We evaluated grey matter volume using voxel-based morphometry, white matter diffusion using tract-based spatial statistics (TBSS), and region-to-network functional connectivity using dual regression in the default mode network and salience network. We tested for differences between the respective carriers and controls, as well as for divergence of those differences. For the divergence contrast, we additionally performed region-of-interest TBSS analyses in known areas of white matter diffusion differences between FTD and AD (i.e., uncinate fasciculus, forceps minor, and anterior thalamic radiation). RESULTS MAPT/GRN carriers did not differ from controls in any modality. APOE4 carriers had lower fractional anisotropy than controls in the callosal splenium and right inferior fronto-occipital fasciculus, but did not show grey matter volume or functional connectivity differences. We found no divergent differences between both carrier-control contrasts in any modality, even in region-of-interest analyses. CONCLUSIONS Concluding, we could not find differences suggestive of divergent pathways of underlying FTD and AD pathology in asymptomatic risk mutation carriers. Future studies should focus on asymptomatic mutation carriers that are closer to symptom onset to capture the first specific signs that may differentiate between FTD and AD.

中文翻译：

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患有额颞叶痴呆和阿尔茨海默氏病风险的认知健康突变携带者中的灰质，白质和功能连接性的多模式MRI。

背景技术额颞痴呆（FTD）和阿尔茨海默氏病（AD）与灰质体积，白质扩散和功能连接性的差异有关。但是，尚不清楚在什么疾病阶段会出现这些差异。在这里，我们调查在病原性FTD突变的认知健康携带者与AD风险增加的认知健康携带者之间，灰质体积，白质扩散和功能连接性是否存在明显差异。方法我们获得了认知健康受试者的多模态磁共振成像（MRI）脑部扫描，其中（n = 39）和没有（n = 36）微管相关蛋白Tau（MAPT）或前颗粒蛋白（GRN）突变，且（n = 37） ）且没有（n = 38）载脂蛋白Eε4（APOE4）等位基因。我们使用基于体素的形态计量学评估了灰质体积，使用基于区域空间统计（TBSS）的白质扩散以及在默认模式网络和显着性网络中使用双重回归评估了区域到网络的功能连通性。我们测试了各个载体和对照之间的差异，以及这些差异的差异。对于差异对比，我们还对FTD和AD之间的白质扩散差异（即束状筋膜，小钳和前丘脑辐射）的已知区域中的感兴趣区域TBSS进行了分析。结果MAPT / GRN携带者在任何形式上均与对照没有区别。在OE骨脾和右下枕额筋膜中，APOE4携带者的分数各向异性低于对照组。但没有显示灰质体积或功能连接性差异。我们发现，即使在感兴趣的区域分析中，任何一种方式的两种载人控制对比之间都没有分歧。结论最后，我们没有发现提示无症状风险突变携带者中潜在FTD和AD病理学差异途径的差异。未来的研究应集中在更接近症状发作的无症状突变携带者上，以捕获可能区分FTD和AD的第一个特定体征。