ALZHEIMER'S DISEASE NEUROIMAGING INITIATIVE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。这项阿尔茨海默病神经影像学倡议（ADNI）是一项评估生物标志物和神经影像学用于评估与阿尔茨海默病（AD）进展相关的变化的建议。共有200名正常人，400名轻度认知障碍（MCI）和200名早期AD受试者将被研究，每个站点16名。该研究将检验PET和/或CT比认知和神经心理学测量更敏感和可靠的AD进展标记的假设。该研究将在2-3年内重复使用测量方法。ADNI的主要目标如下：(a)制定统一的标准，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、多位点MRI和PET数据。(b)取得一般可查阅的数据储存库，其中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)制订方法，最大限度地确定涉及这些病人的试验的治疗效果。(d)验证一系列假设，包括1)海马体积和扣带代谢率预测MCI向AD的转化；2)从MCI到AD的转化率平均为10-15%/年；3)逻辑记忆和APOE4状态的基线得分预测MCI向AD的转化；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：这是一项非随机自然史非治疗研究，在美国和加拿大约50个地点招募800名受试者进行纵向随访，其中包括200名正常对照，400名轻度认知障碍患者和200名轻度AD患者。程序：所有受试者将进行连续的临床/认知评估和1.5 T结构MRI，为期2-3年。大约50%的受试者也将在相同的时间间隔进行FDG PET扫描。25%的受试者（未使用PET扫描）将进行3特斯拉的MRI。AD受试者（n=200）将在0、6、12和24个月时进行研究。将在0、6、12、18、24和36个月时对转化为AD的高风险MCI受试者（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MRI和PET扫描将快速评估质量，以便必要时对受试者进行重新扫描。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志物样本。所有原始和处理过的图像数据将在LONI存档。结果测量：(a)从MCI到AD的转换率。(b)全脑及海马体积变化率。(c)每种指定生物标志物的变化率。(d) PET扫描中指定感兴趣区域的葡萄糖代谢变化率。(e)各组成像和生物标志物测量的差异。

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.