Longitudinal Cognitive ERP studies: Advancement for AD Clinical Trials
纵向认知 ERP 研究:AD 临床试验的进展
基本信息
- 批准号:9120731
- 负责人:
- 金额:$ 95.73万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-09-01 至 2020-04-30
- 项目状态:已结题
- 来源:
- 关键词:AgeAlzheimer disease preventionAlzheimer&aposs DiseaseAmyloidAtrophicAttentionBiological MarkersBrainBrain regionClinicalClinical TrialsCognitionCognitiveCognitive TherapyDataDementiaDiagnostics ResearchDiseaseDisease ProgressionEP300 geneEarly InterventionElderlyElectroencephalographyEnrollmentEventFunctional disorderHealthImpaired cognitionIntervention StudiesKnowledgeLanguageLanguage DisordersLeftLongitudinal StudiesMagnetic Resonance ImagingMeasuresMemantineMemoryMemory LossMethodologyMethodsModalityModelingMolecularNeuronsNeuropsychological TestsOutcomeOutcome MeasureP300 Event-Related PotentialsParticipantPatientsPharmaceutical PreparationsPhysiologicalPopulationPositron-Emission TomographyPrevention trialPrimary PreventionProcessProcess MeasureProtocols documentationRecruitment ActivityResearchResearch InfrastructureSample SizeSamplingShort-Term MemorySpecificityStagingSurrogate MarkersSynapsesTNFRSF5 geneTechniquesTemporal LobeTestingTimeValidationVisualbasecerebral atrophyclinically relevantcognitive changecostdementedfluorodeoxyglucose positron emission tomographyhigh riskhippocampal atrophyimprovedin vivoneuropsychologicalneurotoxicitypotential biomarkerpre-clinicalprognosticprognostic significancetreatment responsetreatment trialvisual memory
项目摘要
DESCRIPTION (provided by applicant): This proposal aims to validate cognitive event-related brain potential (ERP) biomarkers of disease progression in populations eligible to enroll in AD clinical drug trials. We will use a comprehensive ERP protocol which elicits 5 cognitive ERP components (P50, P300, N400, LPC and Frontal Positivity (FP)), each with demonstrated high sensitivity to early Alzheimer disease (AD). A systematic study which compares the relative sensitivity and stability of these ERP components is needed, in this era of validated amyloid biomarkers sensitive to early AD. We will study >200 elderly participants (60 pre-clinical AD, 50 amyloid biomarker - normal elderly, 50 amnestic MCI & 40 mild AD study completers) with longitudinal cognitive ERP/EEG, brain MRI and neuropsychological testing. The project will test the feasibility of multicenter ERP studies, develop infrastructure, refine methodology, and determine how ERPs can be best used to detect the AD pathophysiologic process and to measure changes over time. This study will advance our knowledge of how to use ERPs in AD treatment trials, e.g. for sample "enrichment" in prevention trials, and as outcome measures. Specific Aims: 1) To validate the utility of baseline ERPs in predicting longitudinal trajectories n cognitive decline and brain atrophy. 2) To test the hypothesis that our comprehensive ERP battery will assist the in vivo staging of the AD pathophysiologic process. 3) To test the hypothesis that ERPs are highly sensitive to changes in the AD pathophysiologic process over time and will provide useful biomarkers for tracking disease progression. Methods: We will recruit elderly subjects (age 60-90; n =252, 74 with Preclinical AD (Pre-AD), 62 amyloid biomarker-negative Normal Old (NO) subjects, 62 amnestic MCI, and 54 mild AD dementia). All enrolled subjects will receive an amyloid PET study, longitudinal ERP/EEG and brain MRI. All subjects will be studied with repeat annual ERP testing for 2 years and MRI 1 year after the baseline study, providing longitudinal ERP, structural MRI, neuropsychological and functional data. 32 channel ERP/EEG will be obtained using a comprehensive ERP battery which assesses automatic (P50) and controlled (P300) attention, language (N400) and memory (verbal and visual, with LPC and FP measures) processes. Significance: Sensitive, reliable markers of synaptic dysfunction and incipient AD in its preclinical stages are needed. This proposal, by validating ERP biomarkers of disease progression in populations most relevant to current AD clinical drug trials, will have important applications to primary prevention trials, disease-modifying and targeted cognitive therapies. This study will allow the rational application of specific ERP paradigms, best suited to preclinical vs. prodromal vs. demented populations. More wide application of sensitive ERP/EEG techniques could have major impact on reducing the requisite sample sizes and costs of AD treatment trials.
描述(由申请人提供):这项提案旨在验证有资格参加AD临床药物试验的人群中疾病进展的认知事件相关脑电位(ERP)生物标记物。我们将使用一个全面的ERP方案,它产生5个认知ERP成分(P50,P300,N400,LPC和额叶积极度(FP)),每个成分都对早期阿尔茨海默病(AD)表现出高度敏感。在这个对早期AD敏感的淀粉样蛋白生物标志物被证实的时代,需要一项系统的研究来比较这些ERP组件的相对敏感性和稳定性。我们将研究>;200名老年参与者(60名临床前AD,50名淀粉样生物标志物-正常老年人,50名遗忘型MCI和40名轻度AD研究完成者),进行纵向认知ERP/EEG、脑MRI和神经心理测试。该项目将测试多中心ERP研究的可行性,开发基础设施,改进方法,并确定如何最好地使用ERPs来检测AD的病理生理过程并测量随时间的变化。这项研究将增进我们对如何在AD治疗试验中使用ERPs的知识,例如在预防试验中用于样本“浓缩”,以及作为结果衡量标准。具体目的:1)验证基线事件相关电位在预测认知衰退和脑萎缩的纵向轨迹中的有效性。2)验证我们的综合ERP电池将有助于AD病理生理过程的在体分期的假设。3)验证ERPs对AD病理生理过程随时间的变化高度敏感的假设,并将为追踪疾病进展提供有用的生物标志物。方法:我们将招募老年受试者(60-90岁;n=252,74例临床前阿尔茨海默病(Pre-AD),62例淀粉样蛋白生物标志物阴性的正常老年人(NO),62例遗忘性MCI和54例轻度AD痴呆)。所有登记的受试者将接受淀粉样蛋白PET研究、纵向ERP/EEG和脑MRI。所有受试者都将接受为期两年的重复年度事件相关电位测试,并在基线研究后一年进行磁共振成像,提供纵向事件相关电位、结构磁共振、神经心理学和功能数据。32个通道的ERP/EEG将使用全面的ERP电池获得,该电池评估自动(P50)和受控(P300)注意力、语言(N400)和记忆(语言和视觉,具有LPC和FP测量)过程。意义:需要敏感、可靠的突触功能障碍和临床前阶段的早期AD的标志物。这项建议通过验证与当前AD临床药物试验最相关的人群中疾病进展的ERP生物标记物,将在初级预防试验、疾病修改和有针对性的认知疗法中具有重要应用。这项研究将允许合理应用特定的ERP范例,最适合于临床前、先兆和痴呆人群。更广泛地应用敏感的ERP/EEG技术可能会对减少AD治疗试验所需的样本量和成本产生重大影响。
项目成果
期刊论文数量(0)
专著数量(0)
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会议论文数量(0)
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JAMES B BREWER其他文献
JAMES B BREWER的其他文献
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{{ truncateString('JAMES B BREWER', 18)}}的其他基金
Multidisciplinary training in basic and translational Alzheimer's disease research
阿尔茨海默病基础和转化研究的多学科培训
- 批准号:
10411896 - 财政年份:2020
- 资助金额:
$ 95.73万 - 项目类别:
Multidisciplinary training in basic and translational Alzheimer's disease research
阿尔茨海默病基础和转化研究的多学科培训
- 批准号:
10627977 - 财政年份:2020
- 资助金额:
$ 95.73万 - 项目类别:
UCSD Alzheimer's Disease Research Centers P30
加州大学圣地亚哥分校阿尔茨海默病研究中心 P30
- 批准号:
9924495 - 财政年份:2019
- 资助金额:
$ 95.73万 - 项目类别:
UCSD Alzheimer's Disease Research Centers P30
加州大学圣地亚哥分校阿尔茨海默病研究中心 P30
- 批准号:
10766603 - 财政年份:2019
- 资助金额:
$ 95.73万 - 项目类别:
UCSD Alzheimer's Disease Research Centers P30
加州大学圣地亚哥分校阿尔茨海默病研究中心 P30
- 批准号:
10407977 - 财政年份:2019
- 资助金额:
$ 95.73万 - 项目类别:
UCSD Alzheimer's Disease Research Centers P30
加州大学圣地亚哥分校阿尔茨海默病研究中心 P30
- 批准号:
10615159 - 财政年份:2019
- 资助金额:
$ 95.73万 - 项目类别:
Longitudinal Cognitive ERP studies: Advancement for AD Clinical Trials
纵向认知 ERP 研究:AD 临床试验的进展
- 批准号:
9913431 - 财政年份:2015
- 资助金额:
$ 95.73万 - 项目类别:
Longitudinal Cognitive ERP studies: Advancement for AD Clinical Trials
纵向认知 ERP 研究:AD 临床试验的进展
- 批准号:
9474550 - 财政年份:2015
- 资助金额:
$ 95.73万 - 项目类别:
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