Department of Neurology, Massachusetts General Hospital, Harvard Medical School, and the Martinos Center for Biomedical Imaging, 149/10.008 13th Street, Charlestown, MA 02129, USA.
Department of Radiology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02115, USA.
Neuroimage. 2017 Aug 15;157:612-622. doi: 10.1016/j.neuroimage.2017.05.049. Epub 2017 May 22.
Tau pathology has been associated with neuronal loss at autopsy, but the temporal evolution of tau pathology and atrophy remains unclear. Here, we investigate the association between cross-sectional AV-1451-PET as a marker of tau pathology and cortical thickness cross-sectionally. We also investigated retrospective rates of cortical thinning over the three years preceding the AV-1451 scan in a clinically normal cohort of 103 older adults from the Harvard Aging Brain Study. Tau measurements were Geometric Transfer Matrix partial volume corrected standardized uptake value ratios (SUVRs) with a cerebellar gray reference region. Thirty-four FreeSurfer-defined cortical regions of interest (ROIs) were used for both thickness and AV-1451 in each hemisphere, with seven additional volumetric ROIs. We examined "local" relationships between AV-1451 and cortical thickness in the same ROI, as well as inferior temporal AV-1451 and all thickness ROIs. All models included baseline age and sex, both interacting with time in retrospective longitudinal models, as covariates. Cross-sectional models controlled for the number of days between the two scans. Cross-sectional local comparisons revealed significant associations between elevated AV-1451 and thinner cortical ROIs predominantly in temporal regions, while analyses associating inferior temporal AV-1451 with all cortical ROIs showed a widespread pattern of significant relationships, which was strongest in temporal and parietal cortices. In our retrospective longitudinal analyses, we saw significant relationships in temporal and parietal regions. Significant local relationships were seen in right superior temporal, middle temporal, temporal pole, and fusiform, as well as the left cuneus and banks of the left superior temporal sulcus. Significant relationships between inferior temporal AV-1451 and faster thinning were observed in right temporal regions (middle temporal and fusiform) and bilateral parahippocampal cortices. We observed significant negative relationships between local and inferior temporal AV-1451 signal and both cross-sectional cortical thickness and rates of thinning in lateral and medial temporal regions. This is an important early step toward elucidating the relationship between tau pathology and retrospective longitudinal atrophy in aging and preclinical AD.
tau 病理学与尸检时的神经元丢失有关，但 tau 病理学和萎缩的时间演变仍不清楚。在这里，我们研究了横断面 AV-1451-PET 作为 tau 病理学标志物与皮质厚度的横断面相关性。我们还调查了在哈佛衰老大脑研究中的 103 名老年临床正常队列中，在 AV-1451 扫描前三年皮质变薄的回顾性速率。tau 测量是几何传输矩阵部分体积校正标准化摄取比值 (SUVRs)，以小脑灰质参考区为参照。每侧半球的 34 个 FreeSurfer 定义的皮质感兴趣区 (ROI) 用于厚度和 AV-1451，另外还有 7 个容积 ROI。我们检查了同一 ROI 中 AV-1451 与皮质厚度之间的“局部”关系，以及颞下回 AV-1451 与所有厚度 ROI 之间的关系。所有模型都包括基线年龄和性别，在回顾性纵向模型中，两者都与时间相互作用，作为协变量。横断面模型控制了两次扫描之间的天数。横断面局部比较显示，在颞叶区域，升高的 AV-1451 与皮质 ROI 变薄之间存在显著相关性，而分析将颞下回 AV-1451 与所有皮质 ROI 相关联时，显示出广泛的显著相关性模式，在颞叶和顶叶最强。在我们的回顾性纵向分析中，我们在颞叶和顶叶区域看到了显著的相关性。在右侧颞上、中颞、颞极和梭状回，以及左侧楔前叶和左侧颞上沟的banks 中观察到显著的局部关系。在右侧颞叶区域（中颞和梭状回）和双侧海马旁皮质中观察到颞下回 AV-1451 与更快变薄之间存在显著关系。我们观察到局部和颞下回 AV-1451 信号与外侧和内侧颞叶区域的皮质厚度和变薄率之间存在显著负相关。这是阐明 tau 病理学与衰老和临床前 AD 中回顾性纵向萎缩之间关系的重要的早期步骤。
