ALZEHEIMERS DISEASE NEUROIMAGING PROTOCOL (ADNI)

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 为什么选择ADNI？ 目前，针对AD患者的药物开发成本高昂，需要相当长的时间。目前已上市的药物已开发用于AD的对症治疗，试验可在6个月内完成。旨在减缓疾病改善所需的下降速度的试验需要至少一年或更长的治疗时间才能实现充分的临床分组。用于轻度认知障碍（MCI）受试者的药物开发需要更长时间，因为这些受试者进展更慢。目前的MCI试验需要3-4年来确定足够的临床下降率或足够数量的从MCI到AD的转换以完成临床试验（R.C. Petersen，2003）。MCI受试者特别受关注，因为他们代表了转化为AD的风险特别高的人群和可以进行二级预防试验的人群。在正常受试者的情况下，向AD的转化非常缓慢，根据队列的年龄，平均仅为1- 2%/年。因此，AD的一级预防试验需要3，000 - 6，000例受试者随访5 - 7年，以达到足够的临床终点。这些较长的时间范围是必要的，因为基于斜率分析的临床终点存在大量变异性。例如，ADAS-Cog（AD试验中最广泛使用的认知指标）变化率的标准差是一年变化率的1至1.5倍。在患有MCI或AD的受试者中，全脑、海马或内嗅皮质的体积图像具有比允许检测较小效应量的临床测量更小的变化标准差与萎缩速率的比率（Grundman等人，2002年）。因此，开发跟踪疾病进展并反映潜在病理学变化的合适生物标志物相对于临床/认知数据具有两个优点：1）由于测量误差减少，它们具有更大的统计能力来检测治疗效果，以及2）它们提供可以直接（例如，脑大小的变化、CSF蛋白的测量）指示疾病进展的速率。因此，使用这些生物标志物可以通过提供药物疗效的早期信号来显着加速药物开发。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. WHY ADNI? At present, the development of drugs for patients with AD is costly and requires a considerable length of time. Currently marketed drugs have been developed for symptomatic treatment of AD and trials can be completed in 6 months. Trials designed to slow the rate of decline necessary to demonstrate disease modification require at least one year of treatment or longer to see adequate clinical separation of groups. The development of drugs for subjects with mild cognitive impairment (MCI) takes longer since these subjects progress more slowly. Current MCI trials require 3-4 years to establish either a sufficient rate of clinical decline or a sufficient number of conversions from MCI to AD to complete a clinical trial (R.C. Petersen, 2003). Subjects with MCI are of particular interest since they represent a population at particularly high risk of converting to AD and a population in which secondary prevention trials can be carried out. In the case of normal subjects, conversion to AD is very slow, averaging only 1-2 % / year depending on the age of the cohort. Thus, primary prevention trials for AD require 3,000-6,000 subjects followed for 5 to 7 years to achieve sufficient clinical endpoints. These long timeframes are necessary because there is a great deal of variability in clinical endpoints based on slope analysis. For example, the standard deviation of the rate of change for the ADAS-Cog, the most widely used cognitive measure in AD trials, is 1 to 1.5 times the one year rate of change. In subjects with MCI or AD, volumetric images of the whole brain, hippocampus or entorhinal cortex have a smaller ratio of standard deviation of change to the rate of atrophy than clinical measures allowing for detection of a smaller effect size (Grundman et al., 2002). Thus, the development of suitable biomarkers that track the progression of the disease and reflect change in underlying pathology has two advantages over clinical/cognitive data: 1) They have greater statistical power to detect treatment effects, because of reduced measurement error and 2) They provide measurements which may directly (e.g., changes in brain size, measurements of CSF proteins) indicate rate of disease progression. Therefore, the use of such biomarkers could markedly speed drug development by providing an earlier signal of drug efficacy.