Teipel Stefan J, Flatz Wilhelm H, Heinsen Helmut, Bokde Arun L W, Schoenberg Stefan O, Stöckel Stephanie, Dietrich Olaf, Reiser Maximilian F, Möller Hans-Jürgen, Hampel Harald
Department of Psychiatry, Alzheimer Memorial Center and Geriatric Psychiatry Branch, Dementia and Neuroimaging Section, Ludwig-Maximilian University, Munich, Germany.
Brain. 2005 Nov;128(Pt 11):2626-44. doi: 10.1093/brain/awh589. Epub 2005 Jul 13.
Alzheimer's disease is characterized by the degeneration and loss of cholinergic neurones in the nucleus basalis Meynert, located within the substantia innominata at the ventral surface of the basal forebrain. An in vivo measure of morphological changes in the nucleus basalis Meynert would be of high relevance to better understand the structural correlate of cholinergic dysfunction in Alzheimer's disease. In this study, we applied a newly developed automated technique of image regression analysis, implemented through code written in Matlab 5.3 (MathWorks, Natick, MA), to the analysis of proton density weighted structural MRI of the basal forebrain from 13 patients with Alzheimer's disease (mean age = 77.5 years, SD = 4.4 years, 8 women) and 12 healthy elderly subjects (mean age = 62.3 years, SD = 5.6 years, 6 women). This technique allows searching a large portion of the substantia innominata for signal changes. We used corresponding MRI and histological sections of a post mortem brain to map the locations of basal forebrain cholinergic nuclei into the MRI standard space. Additionally, we used voxel-based morphometry, implemented in SPM2 (Wellcome Department of Imaging Neuroscience, London, UK) to determine correlations between signal changes in the substantia innominata and cortical grey matter atrophy in the patients with Alzheimer's disease. When matching the locations of signal reductions in the in vivo MRI to the template of basal nuclei based on the postmortem brain, signal intensity was decreased in areas corresponding to anterior lateral and anterior medial nucleus basalis Meynert and increased in the third ventricle, the transverse fissure and the optic tract in patients with Alzheimer's disease compared with controls. The reduction of the signal intensity in an area corresponding to the anterior lateral nucleus basalis Meynert was significantly correlated with reduced grey matter concentration in the bilateral prefrontal cortex, inferior parietal lobule and cingulate gyrus. Our findings suggest that signal changes occur in patients with Alzheimer's disease in the substantia innominata which may be related to the loss or degeneration of cholinergic neurones and correspond to regional cortical grey matter atrophy. If replicated in an independent sample, our technique may be useful to detect degeneration of basal forebrain cholinergic neurones in vivo.
阿尔茨海默病的特征是位于基底前脑腹侧无名质内的梅纳特基底核中的胆碱能神经元发生退化和丧失。对梅纳特基底核形态变化进行活体测量，对于更好地理解阿尔茨海默病中胆碱能功能障碍的结构相关性具有高度相关性。在本研究中，我们应用了一种新开发的图像回归分析自动化技术，该技术通过用Matlab 5.3（MathWorks，美国马萨诸塞州纳蒂克）编写的代码实现，对13例阿尔茨海默病患者（平均年龄 = 77.5岁，标准差 = 4.4岁，8名女性）和12名健康老年受试者（平均年龄 = 62.3岁，标准差 = 5.6岁，6名女性）的基底前脑质子密度加权结构MRI进行分析。该技术允许在大部分无名质中搜索信号变化。我们使用死后大脑的相应MRI和组织学切片，将基底前脑胆碱能核的位置映射到MRI标准空间中。此外，我们使用在SPM2（英国伦敦惠康成像神经科学部）中实现的基于体素的形态测量法，来确定阿尔茨海默病患者无名质中的信号变化与皮质灰质萎缩之间的相关性。当将活体MRI中信号降低的位置与基于死后大脑的基底核模板进行匹配时，与对照组相比，阿尔茨海默病患者中对应于梅纳特基底核前外侧和前内侧核的区域信号强度降低，而第三脑室、横裂和视束中的信号强度增加。对应于梅纳特基底核前外侧核区域的信号强度降低与双侧前额叶皮质、顶下小叶和扣带回中灰质浓度降低显著相关。我们的研究结果表明，阿尔茨海默病患者无名质中会出现信号变化，这可能与胆碱能神经元的丧失或退化有关，并与区域皮质灰质萎缩相对应。如果在独立样本中得到重复验证，我们的技术可能有助于在活体中检测基底前脑胆碱能神经元的退化。
