Characterizing Alzheimer's disease molecular and anatomical imaging markers and their relationships with cognition and genetics using machine learning
使用机器学习表征阿尔茨海默病分子和解剖成像标记及其与认知和遗传学的关系
基本信息
- 批准号:10723499
- 负责人:
- 金额:$ 11.91万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-01 至 2028-05-31
- 项目状态:未结题
- 来源:
- 关键词:AffectAlzheimer&aposs DiseaseAlzheimer&aposs disease pathologyAlzheimer&aposs disease patientAmyloidAmyloid beta-ProteinApolipoprotein EBehaviorBehavioralBrainBrain regionClinicalClinical MarkersCognitionCognitiveComplexComputer AssistedDataData SetDementiaDiagnosisDiagnosticDisease OutcomeExhibitsFunctional disorderFutureGene Expression ProfileGeneticGenetic MarkersGoalsHeterogeneityImageKnowledgeMachine LearningMagnetic Resonance ImagingMeasurementMental disordersMethodsMultimodal ImagingNerve DegenerationNeural Network SimulationNeurobiologyNeurodegenerative DisordersNeurofibrillary TanglesOutcomeParticipantPatientsPatternPersonsPhenotypePositron-Emission TomographyPrecision therapeuticsPreparationPsychosesResearchResearch PersonnelScienceSenile PlaquesSubgroupSumSymptomsTechniquesTestingTherapeuticTranslatingUnited StatesUniversitiesVariantWashingtonanatomic imagingbehavioral phenotypingbrain basedclinical phenotypecognitive performancedeep neural networkdesigndisease heterogeneityimaging biomarkerimaging modalityimprovedimproved outcomein vivoinnovationmachine learning methodmachine learning modelmachine learning predictionmagnetic resonance imaging biomarkermental statemild cognitive impairmentmolecular imagingneurobiological mechanismneuroimagingneuropathologyneuropsychiatric disordernovelpatient subsetspolygenic risk scorepre-clinicalprecision medicineprognosticpublic health relevanceresearch clinical testingsuccesssupervised learningsupport vector machinetargeted treatmenttau Proteinstherapeutic biomarkertreatment response
项目摘要
Project Summary
Amyloid-beta and tau are hallmarks of mild cognitive impairment (MCI)/Alzheimer’s disease (AD). The
relationships of in-vivo amyloid-beta, tau, and neurodegeneration with cognitive, clinical, and genetic markers
are not well understood. Patients with AD pathology exhibit heterogeneity in their clinical symptoms and illness
course. Understanding the underlying neurobiological heterogeneity mechanisms of AD and improving the
outcomes have been the central goals. This proposal leverages complementary information of in-vivo amyloid-
beta positron emission tomography (amyloid PET), tau PET, structural magnetic resonance imaging (sMRI),
cognitive, clinical, and genetic measurements via advanced machine learning methods and investigates the
relationships among these measurements in patients with MCI/AD relative to normal controls. The proposal will
study the data from the Alzheimer Disease Neuroimaging Initiative (ADNI; N = 898) and the Washington
University’s Knight Alzheimer Disease Research Center (Knight ADRC; N = 1,121). This study will be the first to
examine regional amyloid PET, tau PET, and sMRI markers and their relationships with cognitive, clinical, and
genetic phenotypes using machine learning predictive modeling and heterogeneity analytics in AD research. The
proposal will quantify regional PET outcomes as distribution volume ratio (DVR) and sMRI as the volumes and
investigate their associations with cognitive [Mini-mental state examination (MMSE)], clinical [clinical dementia
rating sum of boxes (CDR-SB) and CDR], and genetic [polygenic risk scores (PRS) and apolipoprotein E (APOE)]
measurements. Aim 1 will develop machine learning modeling methods to study the relationships of amyloid
PET, tau PET, and sMRI with cognitive and clinical phenotypes and test the hypothesis of whether regional
brain-based imaging measurements exhibit multivariate predictive associations with cognitive and clinical
phenotypes in MCI/AD patients and controls. Aim 2 will study the regional heterogeneity of amyloid PET, tau
PET, and sMRI outcomes via semi-supervised machine learning methods. The study will compare the imaging
outcomes between identified subgroups of patients or controls vs. each subgroup of patients to test the
hypothesis of whether imaging markers differ between subgroups of patients. Aim 3 will examine the
relationships of amyloid PET, tau PET, and sMRI heterogeneity signatures with cognition and genetics to test
whether imaging signatures associate differentially with cognition and genetics in the subgroups of MCI/AD
relative to controls. Overall, this innovative proposal will yield critical information on AD heterogeneity
mechanisms, and contribute to precision medicine of diagnosis and treatment of AD.
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项目摘要
淀粉样蛋白-β和tau是轻度认知障碍(MCI)/阿尔茨海默病(AD)的标志。的
体内淀粉样蛋白β、tau蛋白和神经变性与认知、临床和遗传标记的关系
并没有得到很好的理解。AD病理学患者的临床症状和疾病表现出异质性
当然了了解AD潜在的神经生物学异质性机制,
成果一直是中心目标。该提案利用了体内淀粉样蛋白的补充信息,
β正电子发射断层扫描(淀粉样蛋白PET),tau PET,结构磁共振成像(sMRI),
通过先进的机器学习方法进行认知、临床和遗传测量,并调查
MCI/AD患者相对于正常对照的这些测量之间的关系。该提案将
研究阿尔茨海默病神经影像学倡议(ADNI; N = 898)和华盛顿的数据,
Knight阿尔茨海默病研究中心(Knight ADRC; N = 1,121)。这项研究将是第一个
检查局部淀粉样蛋白PET、tau PET和sMRI标记物及其与认知、临床和
在AD研究中使用机器学习预测建模和异质性分析进行遗传表型分析。的
建议将区域PET结果量化为分布容积比(DVR),将sMRI量化为容积,
研究他们与认知[简易精神状态检查(MMSE)]、临床[临床痴呆]
方框(CDR-SB)和CDR评分总和]和遗传[多基因风险评分(PRS)和载脂蛋白E(APOE)]
测量. Aim 1将开发机器学习建模方法来研究淀粉样蛋白之间的关系
PET、tau PET和sMRI与认知和临床表型的关系,并检验是否存在区域性
基于脑的成像测量显示出与认知和临床
MCI/AD患者和对照的表型。目的2:研究淀粉样蛋白PET、tau蛋白在脑内的区域异质性,
PET和sMRI结果通过半监督机器学习方法。这项研究将比较
确定的患者亚组或对照组与每个患者亚组之间的结局,以检验
假设患者亚组之间的成像标记物是否不同。目标3将审查
淀粉样蛋白PET、tau PET和sMRI异质性特征与认知和遗传学的关系,以测试
在MCI/AD亚组中,成像特征是否与认知和遗传学差异相关
相对于对照。总的来说,这一创新提案将产生关于AD异质性的关键信息
机制,有助于AD的诊断和治疗的精准医学。
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项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
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