Motor, Visual, and Olfactory Changes in Genetic Subtypes of Alzheimer’s Disease
阿尔茨海默病遗传亚型的运动、视觉和嗅觉变化
基本信息
- 批准号:10320928
- 负责人:
- 金额:$ 82.08万
- 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
- 起止时间:2019-02-15 至 2023-11-30
- 项目状态:已结题
- 来源:
- 关键词:AgingAlzheimer&aposs DiseaseAmyloidAnatomyAnosmiaBedsBiological MarkersBlood VesselsBlood capillariesCNS degenerationCessation of lifeClinicalCognitionContrast SensitivityDepositionDeteriorationDevelopmentDiagnosisDifferential DiagnosisDiffusionDiffusion Magnetic Resonance ImagingDisease ManagementDisease ProgressionEquilibriumEsthesiaEtiologyEvaluationEventFutureGaitGait abnormalityGeneticGlaucomaHumanImageKnowledgeLate Onset Alzheimer DiseaseLateral Geniculate BodyMacular degenerationMeasurableMeasuresMemoryMexicanModelingMotorMotor CortexMusculoskeletal SystemMutationNatureOdorsOlfactory PathwaysOptic NerveOpticsPathologyPennsylvaniaPeripheralPeripheral Nervous System DiseasesPersonsPhotophobiaPhysiologic pulsePolyneuropathyPositron-Emission TomographyPrognosisProtocols documentationRadiationReadingResolutionRetinaRiskSensorySmell PerceptionSpeedStandardizationStructureSymptomsTestingThickThinkingThinnessUnited States National Institutes of HealthUniversitiesVisionVisualVisual AcuityVisual PathwaysVisual system structureautosomal dominant Alzheimer&aposs diseasebaseclinically relevantcomorbidityconnectomedensitydisabilityfallsganglion cellgenetic predictorsin vivo imagingmotor deficitmutational statuspre-clinicalpresenilin-1retinal nerve fiber layersenescencetau Proteinstherapeutic targetwalking speed
项目摘要
Title: Motor, Visual, and Olfactory Changes in Genetic Subtypes of Alzheimer's Disease
Though changes in cognition are the most salient features of Alzheimer's disease (AD), subtle
changes in sensation and motor function occur early in the course of AD and might serve as
biomarkers and provide clues as to the cascade of events leading to progressive disability. We will
perform baseline (n = 135) and 3-year f/u evaluations (n = 60) in an ongoing study using the Human
Connectome Project (HCP) protocol of persons of Mexican descent with and at-risk for autosomal
dominant (ADAD) and late-onset AD (LOAD) in order to achieve the following specific aims:
Specific Aim 1a) To define the underlying cause and mechanisms of gait abnormalities in ADAD and
LOAD, we will characterize motor and gait function using the NIH toolbox, the HCP imaging protocol,
and tau PET imaging with flortaucipir.
Specific Aim 1b) To characterize the onset and course of cortical hyperexcitability in ADAD and LOAD
using single-pulse TMS.
Specific Aim 2a) To characterize clinically relevant visual deficits in persons with and at-risk for ADAD
and LOAD using standardized functional measures including logMAR based visual acuity, contrast
sensitivity, as well as low and high contrast reading speed.
Specific Aim 2b) To define the underlying etiology of visual deficits by performing high-resolution, in-
vivo imaging of central and peripheral visual pathway structures including retinal nerve fiber layer
(RNFL), retinal capillary density, volume of optic nerve/chiasm and the lateral geniculate nucleus (LGN)
and connectivity using the HCP.
Specific Aim 3) To characterize deficits in olfaction occurring in persons with and at-risk for ADAD and
LOAD, we will assess olfaction using the University of Pennsylvania Smell Identification Test (UPSIT)
and relate this to tau pathology and connectivity in the olfactory system measured using the HCP.
Comprehensive characterization of motor and sensory changes in ADAD and LOAD could identify
biomarkers for diagnosis, prognosis, and therapeutics targets in the management of the disease.
1
阿尔茨海默病遗传亚型的运动、视觉和嗅觉变化
虽然认知的变化是阿尔茨海默病(AD)最显著的特征,但微妙的
感觉和运动功能的变化发生在AD病程的早期,
生物标志物,并提供线索的级联事件导致进行性残疾。我们将
在一项正在进行的研究中,使用人体模型进行基线(n = 135)和3年随访(n = 60)评价
墨西哥裔常染色体遗传病患者和有常染色体遗传病风险者的连接组项目(HCP)方案
显性AD(ADAD)和迟发性AD(LOAD),以实现以下具体目标:
具体目的1a)确定ADAD患者步态异常的根本原因和机制,
LOAD,我们将使用NIH工具箱、HCP成像方案,
和用flortaucipir进行tau PET成像。
具体目的1b)描述ADAD和LOAD中皮质过度兴奋的发作和病程
使用单脉冲TMS。
具体目的2a)描述ADAD患者和有ADAD风险患者的临床相关视力缺陷
和LOAD使用标准化功能测量,包括基于logMAR的视力、对比度
灵敏度以及低和高对比度阅读速度。
具体目标2b)通过进行高分辨率、高分辨率、高分辨率的视觉检查,
包括视网膜神经纤维层的中枢和外周视觉通路结构的体内成像
(RNFL)、视网膜毛细血管密度、视神经/视交叉和外侧膝状体核(LGN)的体积
以及使用HCP的连通性。
具体目标3)描述ADAD患者和有ADAD风险的患者的嗅觉缺陷,
LOAD,我们将使用宾夕法尼亚大学嗅觉识别测试(UPSIT)评估嗅觉。
并将其与使用HCP测量的嗅觉系统中的tau病理学和连通性相关联。
ADAD和LOAD的运动和感觉变化的综合表征可以识别
用于疾病管理中的诊断、预后和治疗目标的生物标志物。
1
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)
专利数量(0)
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JOHN M RINGMAN其他文献
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{{ truncateString('JOHN M RINGMAN', 18)}}的其他基金
Phenotype and Genotype of Autosomal Dominant Alzheimer's Disease in Jalisco, Mexico
墨西哥哈利斯科州常染色体显性阿尔茨海默病的表型和基因型
- 批准号:
10668453 - 财政年份:2020
- 资助金额:
$ 82.08万 - 项目类别:
Phenotype and Genotype of Autosomal Dominant Alzheimer's Disease in Jalisco, Mexico
墨西哥哈利斯科州常染色体显性阿尔茨海默病的表型和基因型
- 批准号:
10054049 - 财政年份:2020
- 资助金额:
$ 82.08万 - 项目类别:
Phenotype and Genotype of Autosomal Dominant Alzheimer's Disease in Jalisco, Mexico
墨西哥哈利斯科州常染色体显性阿尔茨海默病的表型和基因型
- 批准号:
10475287 - 财政年份:2020
- 资助金额:
$ 82.08万 - 项目类别:
Phenotype and Genotype of Autosomal Dominant Alzheimer's Disease in Jalisco, Mexico
墨西哥哈利斯科州常染色体显性阿尔茨海默病的表型和基因型
- 批准号:
10261579 - 财政年份:2020
- 资助金额:
$ 82.08万 - 项目类别:
Motor, Visual, and Olfactory Changes in Genetic Subtypes of Alzheimer’s Disease
阿尔茨海默病遗传亚型的运动、视觉和嗅觉变化
- 批准号:
10549307 - 财政年份:2019
- 资助金额:
$ 82.08万 - 项目类别:
The structural and functional connectome across Alzheimer's disease subtypes
阿尔茨海默病亚型的结构和功能连接组
- 批准号:
9145149 - 财政年份:2015
- 资助金额:
$ 82.08万 - 项目类别:
The structural and functional connectome across Alzheimer's disease subtypes
阿尔茨海默病亚型的结构和功能连接组
- 批准号:
8969574 - 财政年份:2015
- 资助金额:
$ 82.08万 - 项目类别:
Establishing Infrastructure for Prevention of familial AD in Mexico
在墨西哥建立预防家族性 AD 的基础设施
- 批准号:
8411514 - 财政年份:2013
- 资助金额:
$ 82.08万 - 项目类别:
Establishing Infrastructure for Prevention of familial AD in Mexico
在墨西哥建立预防家族性 AD 的基础设施
- 批准号:
8743128 - 财政年份:2013
- 资助金额:
$ 82.08万 - 项目类别:
Establishing Infrastructure for Prevention of familial AD in Mexico
在墨西哥建立预防家族性 AD 的基础设施
- 批准号:
8770527 - 财政年份:2013
- 资助金额:
$ 82.08万 - 项目类别: