ALZHEIMER'S DISEASE NEUROIMAGING INITIATIVE

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 阿尔茨海默病神经影像学倡议（ADNI）是一项旨在评估生物标志物和神经影像学的使用以评估与阿尔茨海默病（AD）进展相关的变化的建议。 将研究共200例正常受试者、400例轻度认知障碍（MCI）受试者和200例早期AD受试者，每个研究中心16例。 该研究将检验PET和/或CT将是比认知和神经心理学测量更敏感和可靠的AD进展标志物的假设。 该研究将在2-3年内重复测量。 ADNI的主要目标如下：（a）制定统一标准，用于获取阿尔茨海默病（AD）、轻度认知障碍（MCI）和老年对照患者的纵向、多部位MRI和PET数据。(b)获取一个可普遍访问的数据库，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志物数据，以验证成像替代品。(c)在涉及这些患者的试验中，开发能够提供最大功效以确定治疗效果的方法。 (d)检验一系列假设，包括1）海马体积和扣带回代谢率预测MCI向AD的转化; 2）MCI向AD的转化率平均为10-15%/年; 3）逻辑记忆和APOE 4状态的基线评分预测MCI向AD的转化; 4）CSF和血浆异前列烷水平与疾病严重程度相关。 研究设计：这是一项非随机自然史非治疗研究，将在美国和加拿大约50家研究中心招募共计800例受试者，包括200例正常对照、400例MCI患者和200例轻度AD受试者，进行纵向随访。 程序：所有受试者将接受2-3年的系列临床/认知评估和1.5 T结构MRI。 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PET进行扫描）将在3特斯拉下进行MRI。 AD受试者（n=200）将在0、6、12和24个月时接受研究。将在0、6、12、18、24和36个月时研究转化为AD的高风险MCI受试者（n= 400）。 将在0、6、12、24和36个月时研究配对对照组（n=200）。 将快速评估所有MRI和PET扫描的质量，以便在必要时重新扫描受试者。 所有临床数据将由UCSD的协调中心收集、监测和储存。U Penn将收集生物标志物样本。所有原始和处理后的图像数据将在LONI存档。 结果测量：（a）从MCI到AD的转化率。 (b)全脑和海马体积变化率。 (c)每种特定生物标志物的变化率。 (d)PET扫描上特定感兴趣区域的葡萄糖代谢变化率。(e)每个成像和生物标志物测量的组差异。

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.