School of Clinical Medicine, University of Cambridge, Cambridge CB2 0SZ, UK.
Brain. 2010 Feb;133(Pt 2):529-39. doi: 10.1093/brain/awp257. Epub 2009 Nov 13.
Recent imaging evidence in Alzheimer's disease suggests that neural involvement in early-stage disease is more complex than is encapsulated in the commonly held position of predominant mesial temporal lobe degeneration-there is also early posterior cingulate cortex and diencephalic damage. These findings suggest that early clinical Alzheimer's disease is underpinned by damage to an inter-connected network. If correct, this hypothesis would predict degeneration of the white matter pathways that connect this network. This prediction can be tested in vivo by diffusion magnetic resonance imaging. Most diffusion tensor imaging studies of white matter in neurodegenerative disorders such as Alzheimer's disease have concentrated on fractional anisotropy reductions and increased 'apparent' diffusivity; however, there is a lack of empirical biological evidence to assume that fractional anisotropy changes will necessarily capture the full extent of white matter changes in Alzheimer's disease. In this study, therefore, we undertook a comprehensive investigation of diffusion behaviour in Alzheimer's disease by analysing each of the component eigenvalues of the diffusion tensor in isolation to test the hypothesis that early Alzheimer's disease is associated with degeneration of a specific neural network. Using tract-based spatial statistics, we performed voxel-wise analyses of fractional anisotropy, axial, radial and mean diffusivities in 25 Alzheimer's disease patients compared with 13 elderly controls. We found that increased absolute (axial, radial and mean) diffusivities in Alzheimer's disease were concordant in a distribution consistent with the network hypothesis, highly statistically significant and far more sensitive than fractional anisotropy reductions. The former three measures identified confluent white matter abnormalities in parahippocampal gyrus and posterior cingulum, extending laterally into adjacent temporo-parietal regions as well as splenium and fornix. The caudal occipital lobe, temporal pole, genu and prefrontal white matter were relatively preserved. This distribution is highly consistent with expected predictions of tract degeneration from grey matter lesions identified by fluorodeoxyglucose positron emission tomography and structural magnetic resonance imaging. Concordant with results from these other imaging modalities, this pattern predominantly involves degeneration of the tracts connecting the circuit of Papez. These findings also highlight that early neuropathological processes are associated with changes of the diffusion ellipsoid that are predominantly proportional along all semi-principal axes.
最近在阿尔茨海默病中的影像学证据表明，与人们普遍认为的内侧颞叶退化为主的观点相比，早期疾病中的神经受累更为复杂——还有早期的后扣带回和间脑损伤。这些发现表明，早期的临床阿尔茨海默病是由一个相互连接的网络的损伤所支撑的。如果这是正确的，那么这个假设将预测连接这个网络的白质通路的退化。这个预测可以通过弥散磁共振成像在体内进行测试。在神经退行性疾病（如阿尔茨海默病）的大多数弥散张量成像研究中，都集中在分数各向异性的降低和“表观”弥散度的增加上；然而，缺乏经验性的生物学证据来假设分数各向异性的变化必然会捕捉到阿尔茨海默病中白质变化的全部范围。因此，在这项研究中，我们通过单独分析弥散张量的每个组成特征值，对阿尔茨海默病中的弥散行为进行了全面的研究，以检验阿尔茨海默病早期与特定神经网络退化有关的假设。使用基于束的空间统计学，我们对 25 名阿尔茨海默病患者和 13 名老年对照组进行了各向异性分数、轴向、径向和平均弥散度的体素分析。我们发现，阿尔茨海默病患者的绝对（轴向、径向和平均）弥散度增加，其分布与网络假设一致，具有高度统计学意义，比分数各向异性的降低更为敏感。前三个指标在海马旁回和后扣带回发现了融合的白质异常，向外侧延伸到相邻的颞顶区域以及穹窿和穹窿。尾状叶枕叶、颞极、膝部和前额叶白质相对保留。这种分布与氟脱氧葡萄糖正电子发射断层扫描和结构磁共振成像所识别的灰质病变的束退化的预期预测高度一致。与其他成像方式的结果一致，这种模式主要涉及连接 Papez 回路的束的退化。这些发现还强调，早期神经病理学过程与弥散椭球的变化有关，这些变化主要沿着所有半主轴成比例。
