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
项目摘要
大脑白色物质变化在老年人中很常见,并导致不良临床后果。
血管疾病,特别是动脉僵硬,被认为是最普遍的病因基础白色
物质病。动脉僵硬可能导致下游组织缺氧,留下深部白色物质
缺乏侧支供血的血管尤其脆弱。然而,越来越多的证据表明,
病理学,包括淀粉样蛋白-β(Aβ)和过度磷酸化的tau(ptau),作为白色的重要贡献者
物质病。这些病理可能导致与脑白质区域重叠的脑束中的白色物质损伤。
Aβ和ptau沉积,如额叶、颞叶和海马。鉴于有力的证据
提示血管疾病和AD病理相互作用加速临床进展,这些可能是
病理对特别脆弱的白色物质束产生重叠影响,加速认知
下降这项拟议中的研究将检查年龄相关的动脉硬度和体内分子生物标志物,
与白色物质微观结构纵向下降相关的AD病理学(根据扩散张量评估
影像学检查),随访5年。分析将检查白色的完整性与
被确定为特别容易受到每种病理和认知能力下降的影响的物质束。拟议
这项研究将利用范德比尔特大学范德比尔特记忆与阿尔茨海默病中心的丰富资源
范德比尔特,范德比尔特,影像科学研究所,转化临床心血管研究组
高级计算研究和教育中心和范德比尔特大脑研究所。这项研究将
由跨学科导师团队指导,其中包括老年神经心理学、AD、大脑专家
小血管病变,磁共振成像,统计分析,异常临床处理
认知老化和AD分子生物标志物。平行培训计划将有助于候选人
获得必要的知识和技能,研究异常白色疾病的病因,
认知老化,并推动她成为一个成功的职业生涯作为一个独立的医生科学家。理解
与年龄相关的白色物质变化的病因学,特别是特定神经束的脆弱性,
相应的临床后果,将提供有关神经生物学基础的关键信息,
认知能力下降研究结果将提供关于白色物质疾病如何
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