PREDICTING INDIVIDUAL PROGRESSION IN ALZHEIMER'S DISEASE

预测阿尔茨海默病的个体进展

• 批准号: 6933393
• 负责人: NORMAN LOUIS FOSTER
• 金额: $ 12.5万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6933393
• 关键词: Alzheimer' s disease; biomarker; brain metabolism; clinical research; cognition disorders; dementia; disease /disorder onset; human subject; magnetic resonance imaging; neuropathology; neuropsychology; pathologic process; positron emission tomography; postmortem; synapses

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.

虽然我们现在平均知道散发性阿尔茨海默病 (AD) 的症状如何变化，但我们还无法预测个体的痴呆症进展速度有多快，而且我们不明白为什么某些患者的病程比其他患者的恶性程度要高得多。 [18F]氟脱氧葡萄糖正电子发射断层扫描 (FDG-PET) 提供了观察 AD 脑病理发展的窗口。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 可以在症状显现之前识别个体变化，从而作为预测个体疾病进展的生物标志物。在这个项目中，我们将把新主题的图像与 我们已经获得了对正常老年人和尸检证实的 AD 受试者的独特参考 FDG-PET 扫描集，以确认和扩展初步数据，这些数据表明，当脑代谢低下区域较不广泛时，痴呆症进展得更慢。我们将在基线和两年后进行 FDG-PET 和 MRI 扫描，并对一组因 AD 和轻度认知障碍 (MCI)（AD 的常见前驱症状）导致的轻度痴呆患者进行年度临床和神经心理学检查。只要有可能，将进行尸检以确认临床诊断。个体的全球和区域代谢变化将与个体整体痴呆和特定认知领域的变化率进行比较。如果验证为轻度 AD 个体病程的预测因子，则可以使用 FDG-PET 选择更同质的患者群体进行临床试验，评估潜在的疾病缓解治疗的益处，并允许个体化的患者管理。经过 通过识别具有最允许疾病表达的遗传和环境背景的个体，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 治疗的目标。