Brain Aging and Alzheimer's Biomarker Classification Using Amyloid PET, tau PET, and Neurodegeneration on MRI: Developing the ATN system

使用淀粉样蛋白 PET、tau PET 和 MRI 神经变性进行脑衰老和阿尔茨海默病生物标志物分类：开发 ATN 系统

• 批准号: 9915826
• 负责人: CLIFFORD R. JACK
• 金额: $ 73.24万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9915826
• 关键词: Address; Adopted; Age; Aging; Alzheimer' s Disease; Alzheimer' s Disease Pathway; Alzheimer’s disease biomarker; Amyloid; Amyloid beta-42; Amyloidosis; Anatomy; Biological; Biological Markers; Categories; Cerebrovascular Disorders; Cessation of life; Characteristics; Classification; Classification Scheme; Clinic; Clinical; Clinical assessments; Cognitive; Collection; Data; Dementia; Deposition; Development; Diagnostic; Elderly; Frequencies; Functional disorder; Future; General Population; Grant; Grouping; Image; Impaired cognition; Impairment; Individual; Infrastructure; International; Label; Lewy Body Disease; Magnetic Resonance Imaging; Modernization; National Institute on Aging; Nerve Degeneration; Neuronal Injury; Outcome; Paper; Participant; Persons; Positioning Attribute; Positron-Emission Tomography; Prevalence; Publishing; Research; Research Personnel; Scheme; System; Testing; Thick; Tracer; Visit; aged; aging brain; base; clinical risk; cognitive performance; cognitive testing; cohort; falls; fluorodeoxyglucose positron emission tomography; follow-up; imaging biomarker; insight; mild cognitive impairment; novel; population based; sex; tau Proteins; tau-1; working group; Address; Adopted; Age; Aging; Alzheimer' s Disease; Alzheimer' s Disease Pathway; Alzheimer’s disease biomarker; Amyloid; Amyloid beta-42; Amyloidosis; Anatomy; Biological; Biological Markers; Categories; Cerebrovascular Disorders; Cessation of life; Characteristics; Classification; Classification Scheme; Clinic; Clinical; Clinical assessments; Cognitive; Collection; Data; Dementia; Deposition; Development; Diagnostic; Elderly; Frequencies; Functional disorder; Future; General Population; Grant; Grouping; Image; Impaired cognition; Impairment; Individual; Infrastructure; International; Label; Lewy Body Disease; Magnetic Resonance Imaging; Modernization; National Institute on Aging; Nerve Degeneration; Neuronal Injury; Outcome; Paper; Participant; Persons; Positioning Attribute; Positron-Emission Tomography; Prevalence; Publishing; Research; Research Personnel; Scheme; System; Testing; Thick; Tracer; Visit; aged; aging brain; base; clinical risk; cognitive performance; cognitive testing; cohort; falls; fluorodeoxyglucose positron emission tomography; follow-up; imaging biomarker; insight; mild cognitive impairment; novel; population based; sex; tau Proteins; tau-1; working group

PROJECT SUMMARY / ABSTRACT Central insights gained from the first cycle of AG041851 were that the combination of elevated amyloidosis and neurodegeneration greatly increased risk of clinical progression among both clinical normal and mildly impaired persons; and, a novel finding was the definition of an abnormal biomarker category characterized by positive neurodegeneration/neuronal injury biomarkers in the absence of amyloid. We labeled this category suspected non-Alzheimers pathophysiology (SNAP) on the assumption that it represented common non-AD pathologies - e.g., cerebrovascular disease, Lewy body disease, etc. Two modern diagnostic classification systems exist for Alzheimers disease (AD); the National Institute on Aging-Alzheimers Association (NIA-AA) and the International Working Group (IWG). SNAP is not addressed by either of these criteria, yet roughly ¼ of elderly clinically normal (CN) and mild cognitive impairment (MCI) persons fall into this category. In addition, neither the NIA-AA nor the IWG criteria include tau PET for classification. We recently led a large international group of senior investigators in proposing a new, descriptive classification scheme for AD biomarkers (Appendix). The seven most widely regarded AD biomarkers are used to create a 3-class biomarker classification scheme called the ATN system. In the ATN system, amyloid biomarkers are amyloid PET and CSF Aβ42 (denoted by A); tau biomarkers are tau PET and CSF p tau (denoted by T); and, neurodegeneration/neuronal injury biomarkers are FDG PET, anatomic MRI, and CSF t tau (denoted by N). Individuals are classified as positive or negative in each of the three categories leading to eight possible biomarker states (e.g., A-T-N-, A+T+N-, etc.). Neither the NIA-AA nor the IWG criteria categorize individuals in this way and neither addresses the implications of the eight different ATN biomarker permutations. The aims of this renewal grant will focus on understanding the implications of categorizing individuals into these eight ATN classes. We will use amyloid PET to define A, tau PET to define T, and MRI cortical thickness to define N. Given the current emphasis on individuals who are clinically asymptomatic or have very early signs of cognitive impairment, we will concentrate on individuals who are CN and MCI at baseline. Our aims are: Aim 1: To create fully imaged population-based cohorts of CN and MCI individuals aged 30–90 with baseline amyloid PET, tau PET, and MRI studies who will be followed clinically with visits every 15 months. Aim 2: To determine how clinical and demographic characteristics (e.g., age, sex, APOE, indicators of cerebrovascular disease, and baseline cognitive performance) vary across the eight ATN biomarker states. Aim 3: To estimate the age and sex specific prevalence rates of the eight ATN biomarker states. Aim 4: To determine the associations between the eight ATN biomarker states and cognitive or clinical outcomes and whether covariates (e.g., age, sex, APOE, and cerebrovascular disease) modify rates of cognitive decline.

项目摘要 /摘要 从AG041851的第一个周期获得的中央见解是淀粉样变化的组合 神经变性大大增加了临床正常和轻度临床进展的风险 受损的人；而且，一个新颖的发现是以异常生物标志物类别为特征的定义 在没有淀粉样蛋白的情况下，神经变性阳性/神经元损伤生物标志物。我们标记了此类别 可疑的非alzheimers病理生理学（SNAP）假设它代表了常见的非AD 病理 - 例如，脑血管疾病，路易人身体疾病等。两种现代诊断分类 存在于阿尔茨海默氏病（AD）的系统；美国国家老龄化研究所（NIA-AA） 和国际工作组（IWG）。这些标准中的任何一个都没有解决快照，但大约1/4 老年人临床正常（CN）和轻度认知障碍（MCI）属于这一类别。此外， NIA-AA和IWG标准都不包括用于分类的tau PET。我们最近领导了一个大型国际 一组高级调查人员为广告生物标志物提出了新的描述性分类计划 （附录）。七个最广泛的AD生物标志物用于创建3级生物标志物 分类方案称为ATN系统。在ATN系统中，淀粉样生物标志物是淀粉样蛋白宠物， CSFAβ42（由A表示）； tau生物标志物是tau pet和csf p tau（用t表示）；和， 神经变性/神经元损伤生物标志物是FDG PET，解剖MRI和CSF T TAU（由N表示）。 在这三个类别中的每个类别中的每一个中，个人被归类为正面或负面 生物标志物状态（例如A-T-N-，A+T+N-等）。 NIA-AA和IWG标准类别都不 这样，都没有解决八个不同的ATN生物标志物排列的含义。 该更新赠款的目的将集中于理解将个人分类为 这八个ATN课程。我们将使用淀粉样蛋白宠物定义A tau PET定义T和MRI皮质厚度 定义N.鉴于当前对临床无症状或有很早期迹象的个体的强调 认知障碍，我们将专注于基线时CN和MCI的个体。我们的目标是： 目的1：创建完全成像的基于人群的CN和MCI个人的同类，年龄在30-90岁之间 基线淀粉样蛋白宠物，Tau PET和MRI研究，他们将每15个月进行一次临床访问。 目标2：确定临床和人口统计学特征如何（例如，年龄，性别，APOE，指标 在八个ATN生物标志物状态下，脑血管疾病和基线认知性能各不相同。 目标3：估计八个ATN生物标志物州的年龄和性别特定患病率。 目标4：确定八个ATN生物标志物与认知或临床的关联 结果以及协变量（例如年龄，性别，APOE和脑血管疾病）是否修改了 认知能力下降。