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：
7522303
负责人：
CLIFFORD R. JACK
金额：
$ 86.83万
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/7522303
关键词：
6-hydroxybenzothiazole Abbreviations Address Aging Algorithms Alzheimer&apos s Disease Alzheimer&apos s Disease Pathway Amyloid deposition Amyloidosis Anatomy Anisotropy Appendix Applications Grants Attenuated Autopsy Base of the Brain Binding Biological Markers Biology Biostatistical Methods Brain Brain Mapping Brain imaging Cerebrovascular Circulation Chromosome Pairing 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 Knowledge 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 Numbers Outcome Outcome Measure Pathologic Pathology Patient Care Patients Performance Perfusion Pittsburgh Compound-B Population Positron-Emission Tomography Process Proxy Psychometrics Public Health Purpose 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 in vivo interest mild neurocognitive impairment molecular imaging morphometry neuroimaging tool

项目摘要

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：痴呆症代表了一个重大的公共卫生问题，随着我们社会的衰老，它将大大增长。最近，多个收敛的临床和神经病理学数据表明，痴呆通常是一个多因素过程。思考痴呆生物学的这种演变是在痴呆症成像中最重大发展的时候是淀粉样蛋白斑块标记化合物的引入。此时研究最广泛的是匹兹堡化合物-B（PIB）。这种更新的基础是一个中心原则。淀粉样蛋白成像无疑是一个重大进展。但是，由于痴呆症的生物学比单独的脑淀粉样变性更为复杂，因此痴呆的成像比单独的淀粉样蛋白成像更为复杂。我们这种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竞争续约的首次重新提交。我们已经根据批评中提出的每个点进行了修订，我们认为这导致了更强大的应用。五个目标中的每一个都是为了回答问题的变化：基于特定成像的病理学代理对临床/认知能力下降的贡献是什么？在疾病的过程中，这些关系成真？这是真的？相关的病理在大脑中的何处表达？原则结果指标将随着时间的流逝而成为临床和心理测量，我们将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，这些模式将作为痴呆症基础的特定病理机制的代理。 PIB将用作牙菌体负担的量度，我们将使用各种磁共振成像（MRI）模态来评估脑血管疾病，组织损失，组织灌注，扩散，神经元完整性和炎症。将这种更新与AG11378的过去循环区分开的功能包括机械焦点，多种模态成像，包括多种MRI模式以及PET淀粉样蛋白成像，现在在3T处的MR成像，包括Amnestic and Nestic MCI和非动态MCI和非静脉内和无素的基于Voxel的分析方法，包括一个令人兴奋的新计算方法，这些方法采用了一种新的计算方法，该方法旨在采用一个支持Machine Algorith a Sphist Machine Algorith，以支持Mather Algorith。此外，现在将从对基于人群的衰老和痴呆症的新研究中招募受试者，该研究将这种续约与过去的周期以及大多数痴呆症成像研究区分开来，这些研究从转诊实践中招募，从而风险采样偏见。这笔赠款的先前周期对痴呆症成像的效用做出了重大贡献。目前正在就修改AD的临床标准进行积极的辩论，特别是在标准中是否应包括成像和流体生物标志物信息。该更新赠款的结果将为这场辩论提供有关导致痴呆症的多个时间依赖机制的辩论，这些机制可以通过成像在生物中获得。公共卫生相关性：识别痴呆症的机制：MRI在分子成像时代（AG11378）痴呆症的作用现在是一个领先的公共卫生问题，随着老年人数量的增加，公共卫生将对公共卫生产生严重的影响。痴呆症具有许多可能的基本原因，并且在大多数老年痴呆受试者中都在起作用。在这笔赠款中，我们将使用现代的大脑成像来确定痴呆症进展的特定机制。