PREDICTING INDIVIDUAL PROGRESSION IN ALZHEIMER'S DISEASE

虽然我们现在平均知道散发性阿尔茨海默病(AD)的症状是如何变化的，但我们还不能预测一个人痴呆症的发展速度，我们也不明白为什么一些患者的病程比另一些患者的恶性程度要高得多。[18F]氟代脱氧葡萄糖正电子发射断层扫描(FDG-PET)为观察阿尔茨海默病的脑病理发展提供了一个窗口。到目前为止，分子成像研究几乎完全集中在群体变化上。然而，FDG-PET可以在症状变得明显之前识别个体变化，从而作为预测个体疾病进展的生物标记物。在这个项目中，我们将比较新对象中的图像与 在正常的老年人和尸检证实的AD受试者中，我们已经获得了一套独特的参考FDG-PET扫描，以证实和扩展初步数据，这些数据表明，当大脑代谢不足的区域较少时，痴呆症的进展较慢。我们将在基线和两年后进行FDG-PET和MRI扫描，并对因AD和轻度认知障碍(MCI)(AD的常见前驱症状)而导致的轻度痴呆患者进行年度临床和神经心理学检查。如有可能，将进行尸检以确认临床诊断。个人的全球和区域代谢变化将与全球痴呆症和特定认知领域的个人变化率进行比较。如果被确认为轻度AD患者个体病程的预测因子，则有可能使用FDG-PET来选择更同质的患者组进行临床试验，评估潜在疾病修改治疗的益处，并允许个性化的患者管理。通过 确定具有最允许疾病表达的遗传和环境背景的个人，将有可能研究进展的决定因素，这些决定因素本身可能成为新的AD治疗的靶点。

While we now know on average how symptoms change in sporadic Alzheimer's disease (AD), we can't predict yet how rapidly dementia will progress in an individual, and we don't understand why the disease course is so much more malignant in some patients than in others. Positron emission tomography with [18F]fluorodeoxyglucose (FDG-PET) provides a window to observe the development of brain pathology in AD. Thus far, molecular imaging studies have focused almost exclusively on group changes. However, FDG-PET can identify individual changes before symptoms become manifest and thus serve as a biomarker for predicting individual disease progression. In this project, we will compare images in new subjects to a unique set of reference FDG-PET scans in normal elderly and autopsy confirmed AD subjects we have acquired already to confirm and extend preliminary data showing that dementia progresses more slowly when areas of cerebral hypometabolism are less extensive. We will perform FDG-PET and MRI scans at baseline and two years later and perform annual clinical and neuropsychological examinations in a prospective group of patients with mild dementia due to AD and mild cognitive impairment (MCI), a frequent prodrome of AD. Autopsies will be performed to confirm clinical diagnoses whenever possible. Individual global and regional metabolic changes will be compared to individual rates of change in global dementia and specific cognitive domains. If validated as a predictor of individual disease course in mild AD, it will be possible to use FDG-PET to select more homogeneous patient groups for clinical trials, assess the benefits of potential disease-modifying treatments, and permit individualized patient management. By identifying individuals with the most permissive genetic and environmental background for disease expression, it will be possible to study determinants of progression, which themselves could become targets for new AD treatments.