Mahoney Colin J, Ridgway Gerard R, Malone Ian B, Downey Laura E, Beck Jonathan, Kinnunen Kirsi M, Schmitz Nicole, Golden Hannah L, Rohrer Jonathan D, Schott Jonathan M, Rossor Martin N, Ourselin Sebastien, Mead Simon, Fox Nick C, Warren Jason D
Dementia Research Centre, UCL Institute of Neurology, University College London, London, United Kingdom.
Hum Brain Mapp. 2014 Aug;35(8):4163-79. doi: 10.1002/hbm.22468. Epub 2014 Feb 7.
Despite considerable interest in improving clinical and neurobiological characterisation of frontotemporal dementia and in defining the role of brain network disintegration in its pathogenesis, information about white matter pathway alterations in frontotemporal dementia remains limited. Here we investigated white matter tract damage using an unbiased, template-based diffusion tensor imaging (DTI) protocol in a cohort of 27 patients with the behavioral variant of frontotemporal dementia (bvFTD) representing both major genetic and sporadic forms, in relation both to healthy individuals and to patients with Alzheimer's disease. Widespread white matter tract pathology was identified in the bvFTD group compared with both healthy controls and Alzheimer's disease group, with prominent involvement of uncinate fasciculus, cingulum bundle and corpus callosum. Relatively discrete and distinctive white matter profiles were associated with genetic subgroups of bvFTD associated with MAPT and C9ORF72 mutations. Comparing diffusivity metrics, optimal overall separation of the bvFTD group from the healthy control group was signalled using radial diffusivity, whereas optimal overall separation of the bvFTD group from the Alzheimer's disease group was signalled using fractional anisotropy. Comparing white matter changes with regional grey matter atrophy (delineated using voxel based morphometry) in the bvFTD cohort revealed co-localisation between modalities particularly in the anterior temporal lobe, however white matter changes extended widely beyond the zones of grey matter atrophy. Our findings demonstrate a distributed signature of white matter alterations that is likely to be core to the pathophysiology of bvFTD and further suggest that this signature is modulated by underlying molecular pathologies.
尽管人们对改善额颞叶痴呆的临床和神经生物学特征以及明确脑网络解体在其发病机制中的作用有着浓厚兴趣，但关于额颞叶痴呆中白质通路改变的信息仍然有限。在此，我们使用一种基于模板的无偏扩散张量成像（DTI）方案，对27例行为变异型额颞叶痴呆（bvFTD）患者进行了白质束损伤研究，这些患者代表了主要的遗传和散发性形式，同时与健康个体以及阿尔茨海默病患者进行了比较。与健康对照组和阿尔茨海默病组相比，bvFTD组中发现了广泛的白质束病理改变，钩束、扣带束和胼胝体明显受累。相对离散且独特的白质特征与与MAPT和C9ORF72突变相关的bvFTD遗传亚组有关。比较扩散率指标，使用径向扩散率可显示bvFTD组与健康对照组的最佳总体分离，而使用分数各向异性可显示bvFTD组与阿尔茨海默病组的最佳总体分离。在bvFTD队列中比较白质变化与区域灰质萎缩（使用基于体素的形态测量法描绘）发现，两种模式之间存在共定位，特别是在颞叶前部，然而白质变化广泛延伸至灰质萎缩区域之外。我们的研究结果表明，白质改变的分布特征可能是bvFTD病理生理学的核心，并且进一步表明这种特征受潜在分子病理学的调节。
