ALZHEIMER'S DISEASE NEUROIMAGING INITIATIVE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项阿尔茨海默病神经成像倡议(ADNI)是一项建议，旨在评估使用生物标记物和神经成像来评估与阿尔茨海默病(AD)进展相关的变化。共有200名正常受试者、400名轻度认知障碍(MCI)受试者和200名早期AD受试者将被研究，每个站点16人。这项研究将检验这样一种假设，即PET和/或CT将是比认知和神经心理学指标更敏感和可靠的AD进展标志。这项研究将在2-3年内使用重复测量。 ADNI的主要目标如下：(A)为获取阿尔茨海默病(AD)、轻度认知障碍(MCI)和老年对照组患者的纵向、多部位MRI和PET数据制定统一标准。(B)获得一个普遍可用的数据储存库，描述大脑结构和新陈代谢的纵向变化。同时，获取临床认知和生物标记物数据，以验证成像替代物。(C)制定在涉及这些患者的试验中提供最大权力以确定治疗效果的方法。(D)测试一系列假设，包括1)海马体体积和扣带代谢率预测从MCI到AD的转换；2)从MCI到AD的转换率平均为10-15%/年；3)逻辑记忆和APOE4状态的基线分数预测从MCI到AD的转换；4)脑脊液和血浆异前列腺素水平与疾病严重程度相关。 研究设计：这是一项非随机化的自然病史非治疗研究，将在美国和加拿大的大约50个地点招募800名受试者，包括200名正常对照组、400名MCI患者和200名轻度AD患者进行纵向随访。 程序：所有受试者将接受连续的临床/认知评估和1.5T结构磁共振检查，为期2-3年。大约50%的受试者还将在相同的时间间隔进行FDG PET扫描。25%的受试者(未使用正电子发射计算机断层扫描)将在3特斯拉进行核磁共振检查。AD受试者(n=200)将在0、6、12和24个月进行研究。将在0、6、12、18、24和36个月时对MCI高危患者(n=400)进行研究。年龄匹配的对照组(n=200)将在0、6、12、24和36个月时进行研究。所有核磁共振和正电子发射计算机断层扫描的质量将得到快速评估，以便在必要时重新扫描受试者。所有临床数据将由加州大学圣地亚哥分校的协调中心收集、监测和存储。宾夕法尼亚大学将收集生物标记物样本。所有原始和处理后的图像数据将在LONI存档。 观察指标：(A)从MCI转为AD的比率。(B)全脑和海马体体积变化率。(C)每一指明生物标志物的变化率。(D)正电子发射计算机断层扫描特定感兴趣区域的葡萄糖代谢变化率。(E)每次成像和生物标记物测量的组别差异。

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. This Alzheimer's Disease Neuroimaging Initiative (ADNI) is a proposal to evaluate the use of biomarkers and neuroimaging to assess changes associated with the progression of Alzheimer's Disease (AD). A total of 200 normal, 400 mild cognitive impaired (MCI) and 200 early AD subjects will be studied, 16 per site. The study will examine the hypothesis that PET and/or CT will be a more sensitive and reliable marker of AD progression than cognitive and neuropsychological measures. The study will use repeated measures over 2-3 years. The major goals of the ADNI are as follows: (a) Develop uniform standards for acquiring longitudinal, multi-site MRI and PET data on patients with Alzheimer's disease (AD), mild cognitive impairment (MCI), and elderly controls. (b) Acquire a generally accessible data repository which describes longitudinal changes in brain structure and metabolism. In parallel, acquire clinical cognitive and biomarker data for validation of imaging surrogates. (c) Develop methods which will provide maximum power to determine treatment effects in trials involving these patients. (d) Test a series of hypotheses, including 1) hippocampal volume and cingulate metabolic rate predict conversion from MCI to AD; 2) rates of conversion from MCI to AD average 10-15%/year; 3) baseline scores on logical memory and APOE4 status predict conversion from MCI to AD; 4) CSF and plasma isoprostane levels are associated with disease severity. Study Design: This is a non-randomized natural history non-treatment study in which a total of 800 subjects, including 200 normal controls, 400 individuals with MCI, and 200 subjects with mild AD will be recruited at approximately 50 sites in the United States and Canada for longitudinal follow up. Procedures: All subjects will have serial clinical/cognitive assessments and 1.5 T structural MRI for 2-3 years. Approximately 50% of subjects will also have FDG PET scans at the same time intervals. 25% of subjects (who have not been scanned using PET) will have MRI at 3 Tesla. AD subjects (n=200) will be studied at 0, 6, 12, and 24 months. MCI subjects at high risk for conversion to AD (n= 400) will be studied at 0, 6, 12, 18, 24 and 36 months. Age-matched controls (n=200) will be studied at 0, 6, 12, 24 and 36 months. All MRI and PET scans will be rapidly assessed for quality so that subjects may be rescanned if necessary. All clinical data will be collected, monitored, and stored by the Coordinating Center at UCSD. U Penn will collect biomarker samples. All raw and processed image data will be archived at LONI. Outcome Measures: (a) Rate of conversion from MCI to AD. (b) Rate of volume change of whole brain and hippocampus. (c) Rates of change on each specified biomarker. (d) Rates of change of glucose metabolism for specified regions of interest on PET scanning. (e) Group differences for each imaging and biomarker measurement.