PREDICTING INDIVIDUAL PROGRESSION IN ALZHEIMER'S DISEASE

虽然我们现在知道散发性阿尔茨海默病（AD）的平均症状是如何变化的，但我们还不能预测痴呆症在个体中的进展速度有多快，我们也不明白为什么某些患者的病程比其他患者恶性得多。[18F]氟脱氧葡萄糖正电子发射断层扫描（FDG-PET）为观察AD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可以在症状出现之前识别个体变化，因此可以作为预测个体疾病进展的生物标志物。在这个项目中，我们将把新科目中的图像与a进行比较

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.