Examining multiple etiologies underlying white matter disease in aging adults
Examining multiple etiologies underlying white matter disease in aging adults
批准号:
10014557
负责人:
Elizabeth E Moore
金额:
$3.02万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2019
资助国家:
美国
项目状态:
已结题
起止时间:
2019-09-01 至 2023-08-31
关键词:
AdultAffectAgingAlzheimer&aposs DiseaseAlzheimer&aposs disease pathologyAmyloidAmyloid beta-ProteinAmyloidosisAnatomyAreaAutopsyBiological MarkersBlood flowBrainCardiacCardiovascular systemCerebral small vessel diseaseCerebrospinal FluidCerebrumClinicalClinical ManagementCognitive agingDataDementiaDepositionDiffusion Magnetic Resonance ImagingDiseaseEducationElderlyEpisodic memoryEtiologyFunctional disorderGoalsGoldHippocampus (Brain)HypoxiaImageImpaired cognitionIndividualInstitutesKnowledgeLeadLearningLifeLipidsLocationMagnetic Resonance ImagingMeasuresMemoryMemory LossMentorshipMicrocirculationMicrotubulesModelingNeurobiologyNeuropsychologyOligodendrogliaOutcomeParietalPathogenesisPathologicPathologic ProcessesPathologyPathway interactionsPhysiciansPhysiologic pulsePrevalenceResearchResourcesScienceScientistStatistical Data InterpretationStrokeTechniquesTemporal LobeTestingTimeTissuesTrainingUniversitiesVascular DiseasesVascular blood supplyWhite Matter Diseaseabeta accumulationage relatedarterial stiffnesscareerclinical phenotypeexecutive functionfamilial Alzheimer diseasefollow-upfrontal lobehyperphosphorylated tauin vivoinformation processinginsightmemory consolidationmemory retrievalmolecular markernovelprocessing speedskillsvascular injuryvascular risk factorwhite matterwhite matter changewhite matter damage
中文摘要
项目总结
脑白质改变在老年人中很常见,并会导致不良的临床后果。
血管疾病,特别是动脉僵硬,被认为是白人最常见的病因。
物质病。动脉僵硬可能导致下游组织缺氧,留下深部白质
缺乏侧支血液供应的区域特别容易受到伤害。然而,越来越多的证据表明AD有牵连
病理,包括淀粉样蛋白-β(Aβ)和过度磷酸化tau(Ptau),是导致白色的重要因素
物质病。这些病理改变可能导致脑束与脑白质交叠区域的白质损伤
β和Ptau沉积,如额叶、颞叶和海马体。鉴于强有力的证据
提示血管疾病和AD病理相互作用加速临床进展,这是可能的
病理在特别脆弱的白质束上施加重叠效应,加速认知
拒绝。这项拟议的研究将检查与年龄相关的动脉僵硬和体内分子生物标志物。
与白质微结构纵向下降有关的AD病理(根据扩散张量进行评估
成像),为期5年的随访期。分析将检查白色的完整性与
被确定为特别容易受到各种病理和认知衰退影响的物质束。建议数
研究将利用范德比尔特大学范德比尔特记忆和阿尔茨海默氏症中心的丰富资源
影像科学研究所,范德比尔特翻译临床心血管研究组
高级计算研究和教育中心和范德比尔特脑研究所。这项研究将是
由跨学科指导团队指导,其中包括老年神经心理学、阿尔茨海默病、脑
小血管病变、磁共振成像、统计分析、临床异常处理
认知老化和AD分子生物标记物。平行培训计划将有助于应聘者
获得必要的知识和技能来研究异常脑白质病的病因
认知老化,并推动她作为一名独立内科科学家的成功职业生涯。理解
与年龄相关的白质改变的病因学,特别是特定束和
相应的临床结果,将提供关于潜在的神经生物学的关键信息
认知能力下降。研究结果将提供更全面的信息,说明脑白质疾病
整合到AD发病机制中。
英文摘要
PROJECT SUMMARY
Cerebral white matter changes are common in aging adults and contribute to adverse clinical consequences.
Vascular disease, specifically arterial stiffness, is thought to be the most prevalent etiology underlying white
matter disease. Arterial stiffness may lead to hypoxia in downstream tissue, leaving the deep white matter
tracts that lack collateral blood supply especially vulnerable. However, mounting evidence has implicated AD
pathology, including amyloid-β (Aβ) and hyperphosphorylated tau (ptau), as important contributors to white
matter disease. These pathologies may contribute to white matter damage in tracts overlapping with regions of
Aβ and ptau deposition, such as the frontal lobe, temporal lobe, and hippocampus. Given the strong evidence
suggesting vascular disease and AD pathology interact to hasten clinical progression, it is possible that these
pathologies exert overlapping effects on particularly vulnerable white matter tracts, accelerating cognitive
decline. The proposed research will examine age-related arterial stiffness and in vivo molecular biomarkers of
AD pathology in relation to longitudinal decline in white matter microstructure (assessed on diffusion tensor
imaging) over a 5-year follow-up period. Analyses will examine associations between the integrity in white
matter tracts identified as especially vulnerable to each pathology and cognitive decline. The proposed
research will leverage the rich resources of the Vanderbilt Memory & Alzheimer’s Center, Vanderbilt University
Institute of Imaging Science, Vanderbilt Translational Clinical Cardiovascular Research Group, Vanderbilt
Advanced Computing Center for Research and Education, and Vanderbilt Brain Institute. The research will be
guided by an interdisciplinary mentorship team, including experts in geriatric neuropsychology, AD, cerebral
small vessel disease, magnetic resonance imaging, statistical analysis, clinical management of abnormal
cognitive aging, and AD molecular biomarkers. The parallel training plan will facilitate the candidate’s
acquisition of the necessary knowledge and skills to study the etiologies of white matter disease in abnormal
cognitive aging and propel her into a successful career as an independent physician scientist. Understanding
the etiology of age-related white matter changes, especially the vulnerability of specific tracts and
corresponding clinical consequences, would provide critical information regarding the neurobiology underlying
cognitive decline. Findings will offer more comprehensive information regarding how white matter disease
integrates into AD pathogenesis.
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会议论文
Examining multiple etiologies underlying white matter disease in aging adults
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批准号:10214485
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项目类别:
-
资助金额:$4.04万
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财政年份:2019
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负责人:Elizabeth E Moore
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依托单位:
海外基金