Department of Biomedical Engineering, Johns Hopkins University, 3400 N Charles St, Baltimore 21218, MD, USA.
Department of Biomedical Engineering, Johns Hopkins University, 3400 N Charles St, Baltimore 21218, MD, USA.
Neuroimage Clin. 2023;38:103374. doi: 10.1016/j.nicl.2023.103374. Epub 2023 Mar 15.
Previous research has emphasized the unique impact of Alzheimer's Disease (AD) pathology on the medial temporal lobe (MTL), a reflection that tau pathology is particularly striking in the entorhinal and transentorhinal cortex (ERC, TEC) early in the course of disease. However, other brain regions are affected by AD pathology during its early phases. Here, we use longitudinal diffeomorphometry to measure the atrophy rate from MRI of the amygdala compared with that in the ERC and TEC in cognitively unimpaired (CU) controls, CU individuals who progressed to mild cognitive impairment (MCI), and individuals with MCI who progressed to dementia of the AD type (DAT), using a dataset from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Our results show significantly higher atrophy rates of the amygdala in both groups of 'converters' (CU→MCI, MCI→DAT) compared to controls, with rates of volume loss comparable to rates of thickness loss in the ERC and TEC. We localize atrophy within the amygdala within each of these groups using fixed effects modeling. Controlling for the familywise error rate highlights the medial regions of the amygdala as those with significantly higher atrophy in both groups of converters than in controls. Using our recently developed method, referred to as Projective LDDMM, we map measures of neurofibrillary tau tangles (NFTs) from digital pathology to MRI atlases and reconstruct dense 3D spatial distributions of NFT density within regions of the MTL. The distribution of NFTs is consistent with the spatial distribution of MR measured atrophy rates, revealing high densities (and atrophy) in the amygdala (particularly medial), ERC, and rostral third of the MTL. The similarity of the location of NFTs in AD and shape changes in a well-defined clinical population suggests that amygdalar atrophy rate, as measured through MRI may be a viable biomarker for AD.
先前的研究强调了阿尔茨海默病（AD）病理学对内侧颞叶（MTL）的独特影响，这反映了在疾病早期，tau 病理学在内嗅皮质和跨内嗅皮质（ERC、TEC）中尤为明显。然而，在疾病的早期阶段，其他大脑区域也会受到 AD 病理学的影响。在这里，我们使用纵向变分测量法来测量与认知正常（CU）对照组、从认知正常进展为轻度认知障碍（MCI）的 CU 个体以及从 MCI 进展为 AD 型痴呆（DAT）的个体相比，MRI 测量的杏仁核萎缩率，使用来自阿尔茨海默病神经影像学倡议（ADNI）的数据集。我们的结果表明，两组“转化者”（CU→MCI，MCI→DAT）的杏仁核萎缩率均显著高于对照组，体积损失率与 ERC 和 TEC 的厚度损失率相当。我们使用固定效应模型在每个组内定位杏仁核的萎缩。控制总体错误率突出了杏仁核的内侧区域，在两组转化者中，其萎缩程度明显高于对照组。使用我们最近开发的方法，称为投影 LDDMM，我们将神经纤维缠结（NFT）的测量值从数字病理学映射到 MRI 图谱，并在 MTL 区域内重建 NFT 密度的密集 3D 空间分布。NFT 的分布与 MRI 测量的萎缩率的空间分布一致，揭示了杏仁核（特别是内侧）、ERC 和 MTL 的前 3 分之一区域的高密度（和萎缩）。AD 中 NFT 的位置与明确临床人群中形状变化的相似性表明，通过 MRI 测量的杏仁核萎缩率可能是 AD 的一种可行的生物标志物。
