Identifying Mechanisms of Dementia: Role for MRI in the Era of Molecular Imaging

识别痴呆症的机制：MRI 在分子成像时代的作用

基本信息

批准号：
8117482
负责人：
CLIFFORD R. JACK
金额：
$ 96.84万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
1993
资助国家：
美国
起止时间：
1993-06-01 至 2013-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8117482
关键词：
6-hydroxybenzothiazole Abbreviations Address Aging Algorithms Alzheimer&apos s Disease Alzheimer&apos s Disease Pathway Amyloid deposition Amyloidosis Anatomy Anisotropy Applications Grants Attenuated Autopsy Base of the Brain Binding Biological Markers Biology Biostatistical Methods Brain Brain Mapping Brain imaging Cerebrovascular Circulation Classification Clinic Clinical Clinical Pathology Cognition Cognitive Complex Correlation Studies Critiques Data Data Set Dementia Development Diagnosis Diagnostic Diffusion Diffusion Magnetic Resonance Imaging Disease Disease Progression Elderly Enrollment Epidemiologic Studies Event Evolution Future Goals Grant Health Image Image Analysis Impaired cognition Individual Inflammation Inositol Label Life Liquid substance Location Machine Learning Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Maps Measures Memory Methods Metric Modality Modeling N-acetylaspartate Neurofibrillary Tangles Neurons Outcome Outcome Measure Pathologic Pathology Patient Care Patients Performance Perfusion Pittsburgh Compound-B Population Positron-Emission Tomography Process Proxy Psychometrics Public Health Recovery Recruitment Activity Relative (related person)Resolution Risk Role Sampling Sampling Biases Scheme Senile Plaques Severity of illness Societies Spin Labels Staging Study Subject Symptoms Synapses Syndrome Text Thinking Time Tissues Variant Vascular Diseases Work amyloid imaging base clinical Diagnosis cohort imaging modality in vivo interest mild neurocognitive impairment molecular imaging morphometry neuroimaging population based primary outcome tool

项目摘要

Dementia represents a major public health problem which will grow significantly with the aging of our society. Recently, multiple pieces of converging clinical and neuropathological data indicate that dementia is typically a multi-factorial process. This evolution in thinking about the biology of dementia comes at a time when the most significant recent development in dementia imaging has been the introduction of amyloid plaque labeling compounds; the most widely studied at this point is Pittsburgh Compound - B (PiB). A central principle underlying this renewal is this. Amyloid imaging is unquestionably a major advance. However, since the biology of dementia is more complex than brain amyloidosis alone, imaging of dementia is more complex than brain amyloid imaging alone. Our primary goal in this renewal is to use various imaging modalities to identify different mechanisms underlying dementia. This is the first resubmission of a competitive renewal of AG11378. We have revised the grant in accordance with each point raised in the critique and we believe this has resulted in a much stronger application. Each of the five aims is cast to answer variations on the questions: What is the contribution of specific imaging-based proxies of pathology to clinical/cognitive decline? When in the course of the disease do these relationships hold true? For whom is this true? Where in the brain are the relevant pathologies expressed? Principle outcome measures will be clinical and psychometric decline over time which we will use as indicators of disease progression. Our predictor variables will include various imaging modalities which will serve as proxies for specific pathologic mechanisms underlying dementia. PiB will serve as a measure of plaque burden and we will use various Magnetic Resonance Imaging (MRI) modalities to assess cerebro- vascular disease, tissue loss, tissue perfusion, diffusion, neuronal integrity, and inflammation. Features that distinguish this renewal from past cycles of AG11378 include a mechanistic focus, multi- modality imaging including multiple MRI modalities as well as PET amyloid imaging, MR imaging now at 3T, inclusion of both amnestic and non-amnestic MCI, and voxel-based analytic methods including an exciting new computational approach which employs a support vector machine algorithm to provide diagnosis in individual subjects. In addition, subjects will now be recruited from a new population-based study of aging and dementia, which differentiates this renewal from past cycles as well as from most dementia imaging studies which recruit from referral practices and thus risk sampling bias. Previous cycles of this grant have contributed significantly to recognition of the utility of imaging in dementia. An active debate is currently underway about revising clinical criteria for AD, specifically whether imaging and fluid biomarker information should be included among the criteria. Results from this renewal grant will inform this debate about multiple time dependent mechanisms leading to dementia that are accessible in living subjects through imaging. PUBLIC HEALTH RELEVANCE: Identifying Mechanisms of Dementia: Role for MRI in the Era of Molecular Imaging (AG11378) Dementia is a leading public health problem now and will have an increasingly serious impact on public health as the number of elderly individuals increase. Dementia has many possible underlying causes and several different causes are at work in most elderly demented subjects. In this grant, we will use modern brain imaging to identify specific mechanisms underlying progression to dementia.

痴呆症是一个重大的公共卫生问题，随着社会的老龄化，该问题将显着加剧。最近，多项临床和神经病理学数据表明，痴呆症通常是一个多因素的过程。痴呆症生物学思维的这种演变发生在痴呆症成像领域最近最重要的发展是淀粉样斑块标记化合物的引入之际。目前研究最广泛的是匹兹堡化合物 - B (PiB)。这一更新的核心原则是这样的。淀粉样蛋白成像无疑是一项重大进步。然而，由于痴呆症的生物学比单独的脑淀粉样变性更复杂，因此痴呆症的成像比单独的脑淀粉样蛋白成像更复杂。我们这次更新的主要目标是使用各种成像方式来识别痴呆症的不同机制。这是 AG11378 竞争性续展的首次重新提交。我们根据批评中提出的每一点修改了拨款，我们相信这导致了更强有力的申请。这五个目标中的每一个都旨在回答以下问题的不同变化：特定的基于成像的病理学代理对临床/认知衰退有何贡献？在疾病过程中，这些关系何时成立？对于谁来说这是真的？相关病理在大脑的哪个部位表达？主要结果指标是临床和心理测量随着时间的推移而下降，我们将其用作疾病进展的指标。我们的预测变量将包括各种成像方式，这些方式将作为痴呆症的特定病理机制的代表。 PiB 将作为斑块负荷的衡量标准，我们将使用各种磁共振成像 (MRI) 模式来评估脑血管疾病、组织损失、组织灌注、扩散、神经元完整性和炎症。此次更新与 AG11378 过去周期的区别包括机械焦点、多模态成像（包括多种 MRI 模态以及 PET 淀粉样蛋白成像）、现在 3T 的 MR 成像、包括遗忘和非遗忘 MCI，以及基于体素分析方法包括令人兴奋的新计算方法，该方法采用支持向量机算法来为个体受试者提供诊断。此外，现在将从一项新的基于人群的老龄化和痴呆症研究中招募受试者，这将这种更新与过去的周期以及大多数痴呆成像研究区分开来，这些研究是从转诊实践中招募的，因此存在抽样偏差的风险。该资助的前几轮为人们认识到成像在痴呆症中的效用做出了重大贡献。目前，关于修订 AD 临床标准的争论正在进行中，特别是是否应将影像学和液体生物标志物信息纳入标准中。这项续签拨款的结果将为这场关于导致痴呆症的多种时间依赖性机制的争论提供信息，这些机制可以通过成像在活体受试者中获得。公共卫生相关性：识别痴呆症的机制：MRI 在分子成像时代的作用 (AG11378) 痴呆症现在是一个主要的公共卫生问题，并且随着老年人数量的增加，将对公众健康产生越来越严重的影响。痴呆症有许多可能的根本原因，并且有几种不同的原因在大多数老年痴呆症受试者中起作用。在这笔拨款中，我们将使用现代脑成像技术来确定痴呆症进展的具体机制。