de Leon M J, Mosconi L, Blennow K, DeSanti S, Zinkowski R, Mehta P D, Pratico D, Tsui W, Saint Louis L A, Sobanska L, Brys M, Li Y, Rich K, Rinne J, Rusinek H
Center for Brain Health, NYU School of Medicine, Department of Psychiatry, 560 First Ave., New York 10016, USA.
Ann N Y Acad Sci. 2007 Feb;1097:114-45. doi: 10.1196/annals.1379.012.
It is widely believed that the path to early and effective treatment for Alzheimer's disease (AD) requires the development of early diagnostic markers that are both sensitive and specific. To this aim, using longitudinal study designs, we and others have examined magnetic resonance imaging (MRI), 2-fluoro-2-deoxy-d-glucose-positron emission tomography (FDG/PET), and cerebrospinal fluid (CSF) biomarkers in cognitively normal elderly (NL) subjects and in patients with mild cognitive impairment (MCI). Such investigations have led to the often replicated findings that structural evidence of hippocampal atrophy as determined by MRI, as well as metabolic evidence from FDG-PET scan of hippocampal damage, predicts the conversion from MCI to AD. In this article we present a growing body of evidence of even earlier diagnosis. Brain pathology can be detected in NL subjects and used to predict future transition to MCI. This prediction is enabled by examinations revealing reduced glucose metabolism in the hippocampal formation (hippocampus and entorhinal cortex [EC]) as well as by the rate of medial temporal lobe atrophy as determined by MRI. However, neither regional atrophy nor glucose metabolism reductions are specific for AD. These measures provide secondary not primary evidence for AD. Consequently, we will also summarize recent efforts to improve the diagnostic specificity by combining imaging with CSF biomarkers and most recently by evaluating amyloid imaging using PET. We conclude that the combined use of conventional imaging, that is MRI or FDG-PET, with selected CSF biomarkers incrementally contributes to the early and specific diagnosis of AD. Moreover, selected combinations of imaging and CSF biomarkers measures are of importance in monitoring the course of AD and thus relevant to evaluating clinical trials.
人们普遍认为，要实现阿尔茨海默病（AD）的早期有效治疗，需要开发出兼具敏感性和特异性的早期诊断标志物。为此，我们和其他研究团队采用纵向研究设计，对认知正常的老年人（NL）和轻度认知障碍（MCI）患者进行了磁共振成像（MRI）、2-氟-2-脱氧-D-葡萄糖正电子发射断层扫描（FDG/PET）以及脑脊液（CSF）生物标志物的检测。这些研究常常得出重复性结果，即MRI确定的海马萎缩结构证据以及FDG-PET扫描显示的海马损伤代谢证据可预测MCI向AD的转化。在本文中，我们展示了越来越多关于更早期诊断的证据。脑病理学改变可在NL受试者中检测到，并用于预测未来向MCI的转变。这种预测可通过检查发现海马结构（海马和内嗅皮质[EC]）葡萄糖代谢降低以及MRI确定的内侧颞叶萎缩速率来实现。然而，无论是局部萎缩还是葡萄糖代谢降低都并非AD所特有。这些指标为AD提供的是次要而非主要证据。因此，我们还将总结近期通过将影像学与CSF生物标志物相结合，以及最近通过评估PET淀粉样蛋白成像来提高诊断特异性的努力。我们得出结论，传统影像学检查（即MRI或FDG-PET）与选定的CSF生物标志物联合使用，逐步有助于AD的早期特异性诊断。此外，影像学和CSF生物标志物测量的选定组合对于监测AD病程很重要，因此与评估临床试验相关。
