Validating the New Criteria for Preclinical Alzheimer's disease
验证临床前阿尔茨海默病的新标准
基本信息
- 批准号:8828533
- 负责人:
- 金额:$ 50.73万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-04-01 至 2016-03-31
- 项目状态:已结题
- 来源:
- 关键词:AgreementAlzheimer&aposs DiseaseAlzheimer&aposs Disease PathwayAlzheimer&aposs disease modelAmyloidAmyloidosisAppearanceApplications GrantsBiological MarkersBrainCerebrumClassificationClinicalCognitiveCognitive deficitsDementiaDiagnosisDiagnosticDiseaseDrug FormulationsElderlyFunctional disorderFutureGoalsGuidelinesIndividualLeftModelingNational Institute of Neurological Disorders and StrokeNational Institute on AgingNerve DegenerationNeurobehavioral ManifestationsNeuronal InjuryNormal RangePersonsPhasePopulation DistributionsPositron-Emission TomographyProcessProxyPubMedPublishingQualifyingSeveritiesSpecific qualifier valueStagingStaging SystemSymptomsSynapsesUpdateValidationadvanced diseasebaseclinical Diagnosiscognitive changecognitive performancecognitive testingcohortfallsfollow-upfrontiermild cognitive impairmentpopulation basedpre-clinicalstandard measure
项目摘要
DESCRIPTION (provided by applicant): In 2010, the Alzheimer's Association (AA), National Institute on Aging (NIA) and National Institute of Neurological Disorders and Stroke formed three workgroups to revise diagnostic guidelines for Alzheimer's disease (AD) that had been employed since 1984. The preclinical workgroup devised guidelines for a stage of the disease that had not yet been formally defined. Most in the field believe that successful disease modifying treatment of AD will require that treatment begin prior to onset of dementia and perhaps prior to overt clinical symptoms (i.e. MCI). Thus, validation of the new preclinical AD criteria is a major new investigational frontier. The preclinical phase of AD is defined by abnormal AD biomarker studies with no, or only subtle, cognitive deficits. At present, there are five major AD biomarkers which fall into two classes: 1) biomarkers of brain Ab amyloidosis and 2) biomarkers of neuronal injury. The preclinical criteria describe three stages of preclinical AD that represent incrementally more advanced disease: Stage 1 - Asymptomatic cerebral amyloidosis. Stage 2 - Amyloid positivity plus evidence of synaptic dysfunction and/or early neurodegeneration. Stage 3 - Amyloid positivity plus evidence of neurodegeneration plus subtle cognitive symptoms. While formulation of the new criteria alone represents an advance, there were many issues left unaddressed, the major one being: "Are the criteria valid?".In addition, many issues necessary for operationalization of the criteria were not specified. Our overall goal in this grant proposal is to assess the validity of the new NIA-AA preclinical AD criteria. A necessary first step in operationalizing and assessing the validity of the criteria is to develop ct-points or thresholds for different biomarkers and cognitive tests to identify cognitively normal elderly subjects with abnormal biomarker values or subtle cognitive deficits. We have five Specific Aims: Aim 1: To create a cohort of AD subjects (1a) and cognitively normal subjects (1b) who have all 5 biomarkers. Aim 2: To develop cut-points for each biomarker (Aim 2a), evaluate the agreement between biomarkers of the same class (Aim 2b) and develop cut-points for subtle cognitive change (Aim 2c). Aim 3: To use the findings from Aim 2 to estimate the distribution of subjects that fall into preclinical stages in an elderly population-based cohort. Am 4: To determine how well the stages of the new criteria for Preclinical AD predict progression to mild cognitive impairment or dementia (Aim 4a) and to determine the association of the stages of Preclinical AD with decline on serial cognitive testing (Aim 4b). Aim 5: To revise cut-points and re-estimate the distribution of subjects that fall into preclinical stages based on clinical follow-up and longitudinal cognitive testing and compare these with cross-sectionally derived cut-points from Aim 2 and the population distribution of Preclinical AD stages from Aim 3.
描述(由申请人提供):2010年,阿尔茨海默病协会(AA)、国家老龄化研究所(NIA)和国家神经疾病和中风研究所组成了三个工作组,以修订自1984年以来一直采用的阿尔茨海默病(AD)诊断指南。临床前研究人员为尚未正式定义的疾病阶段制定了指导方针。本领域的大多数人认为,AD的成功的疾病改善治疗将需要在痴呆发作之前并且可能在明显的临床症状(即MCI)之前开始治疗开始。因此,新的临床前AD标准的验证是一个主要的新的研究前沿。 AD的临床前阶段由不具有或仅具有轻微认知缺陷的异常AD生物标志物研究定义。目前,存在五种主要的AD生物标志物,其分为两类:1)脑Ab淀粉样变性的生物标志物和2)神经元损伤的生物标志物。临床前标准描述了临床前AD的三个阶段,其代表逐渐更晚期的疾病:第1阶段-无症状脑淀粉样变性。阶段2 -淀粉样蛋白阳性加上突触功能障碍和/或早期神经变性的证据。阶段3 -淀粉样蛋白阳性加上神经变性的证据加上微妙的认知症状。虽然新标准的制定本身就是一个进步,但还有许多问题没有解决,主要的问题是:“标准是否有效?“此外,没有具体说明实施标准所需的许多问题。 我们的总体目标是评估新的NIA-AA临床前AD标准的有效性。操作和评估标准有效性的必要的第一步是为不同的生物标志物和认知测试开发ct点或阈值,以识别具有异常生物标志物值或轻微认知缺陷的认知正常的老年受试者。我们有五个具体目标:目标1:建立一组AD受试者(1a)和认知正常受试者(1b),他们具有所有5种生物标志物。目标二:为每种生物标志物制定临界点(目标2a),评价同类生物标志物之间的一致性(目标2b),并制定细微认知变化的临界点(目标2c)。目标三:使用目标2的结果估计老年人群队列中临床前阶段受试者的分布。上午4:确定临床前AD新标准的分期预测进展为轻度认知障碍或痴呆的程度(目标4a),并确定临床前AD分期与系列认知测试下降的相关性(目标4 b)。目标5:根据临床随访和纵向认知测试,修订临界点并重新估计临床前阶段受试者的分布,并将其与目标2的横断面临界点和目标3的临床前AD阶段人群分布进行比较。
项目成果
期刊论文数量(0)
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CLIFFORD R. JACK其他文献
CLIFFORD R. JACK的其他文献
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{{ truncateString('CLIFFORD R. JACK', 18)}}的其他基金
SCAN: Standardized Centralized Alzheimer's and Related Dementias Neuroimaging
SCAN:标准化集中式阿尔茨海默病和相关痴呆症神经影像学
- 批准号:
10400153 - 财政年份:2020
- 资助金额:
$ 50.73万 - 项目类别:
SCAN: Standardized Centralized Alzheimer's and Related Dementias Neuroimaging
SCAN:标准化集中式阿尔茨海默病和相关痴呆症神经影像学
- 批准号:
9976317 - 财政年份:2020
- 资助金额:
$ 50.73万 - 项目类别:
SCAN: Standardized Centralized Alzheimer's and Related Dementias Neuroimaging
SCAN:标准化集中式阿尔茨海默病和相关痴呆症神经影像学
- 批准号:
10335694 - 财政年份:2020
- 资助金额:
$ 50.73万 - 项目类别:
SCAN: Standardized Centralized Alzheimer's and Related Dementias Neuroimaging
SCAN:标准化集中式阿尔茨海默病和相关痴呆症神经影像学
- 批准号:
10819797 - 财政年份:2020
- 资助金额:
$ 50.73万 - 项目类别:
Multiple System Atrophy - Novel Targets in Early Diagnosis, Pathophysiology, and Therapeutic Approach
多系统萎缩——早期诊断、病理生理学和治疗方法的新目标
- 批准号:
9113684 - 财政年份:2015
- 资助金额:
$ 50.73万 - 项目类别:
Multiple System Atrophy - Novel Targets in Early Diagnosis, Pathophysiology, and Therapeutic Approach
多系统萎缩——早期诊断、病理生理学和治疗方法的新目标
- 批准号:
9328184 - 财政年份:2015
- 资助金额:
$ 50.73万 - 项目类别:
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 - 财政年份:2012
- 资助金额:
$ 50.73万 - 项目类别:
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:
10163755 - 财政年份:2012
- 资助金额:
$ 50.73万 - 项目类别:
Validating the New Criteria for Preclinical Alzheimer's disease
验证临床前阿尔茨海默病的新标准
- 批准号:
8451426 - 财政年份:2012
- 资助金额:
$ 50.73万 - 项目类别:
Validating the New Criteria for Preclinical Alzheimer's disease
验证临床前阿尔茨海默病的新标准
- 批准号:
8273143 - 财政年份:2012
- 资助金额:
$ 50.73万 - 项目类别: