Exceptional Aging: Identifying Modifiers of Alzheimer's Disease Trajectories
Exceptional Aging: Identifying Modifiers of Alzheimer's Disease Trajectories
批准号:
9361654
负责人:
PRASHANTHI VEMURI
金额:
$79.17万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2017
资助国家:
美国
项目状态:
已结题
起止时间:
2017-09-15 至 2022-05-31
关键词:
AccountingAgeAge-YearsAgingAlzheimer&aposs DiseaseAmyloidAmyloid depositionBlood PressureBlood VesselsCardiacCerebrovascular DisordersClinicCognitionCognitiveComputerized Medical RecordDataDementiaDepositionDiagnosisDisease OutcomeEpidemiologyEquationGenesGeneticGenetic ScreeningGenetic VariationGenomicsHealthImageImpaired cognitionIndividualKnowledgeLife StyleLipidsLongevityMeasurementMedical Record LinkageMetabolicMethodologyMethodsMiningModelingNeurodegenerative DisordersNeuropsychologyNormal RangeOccupationsParticipantPathologyPathway interactionsPharmaceutical PreparationsPhysical activityPopulationPositron-Emission TomographyPrevention trialProthrombinPulse PressureResearch InfrastructureResidual stateRiskSamplingScanningSex EducationSystemTestingTranslatingTranslationsVascular Diseasesagedamyloid imagingbasebench to bedsidecognitive changecognitive reservedesigngenomic variationimaging biomarkerindividualized preventionmathematical modelmiddle agepersonalized medicinepopulation basedrate of changeresearch studysuccesstau Proteinstau aggregationtreatment trial
中文摘要
项目摘要/摘要
英文摘要
PROJECT SUMMARY / ABSTRACT
Protection against Alzheimer's disease (AD) dementia has two main components: protection against
Alzheimer's disease pathology (ADP – amyloid and tau) and protection against cognitive impairment despite
ADP (cognitive reserve). Here, we propose an “exceptional aging” hypothesis, where some subjects (>85
years of age) have no significant ADP and are cognitively normal due to protective factors against both ADP
and cognitive decline across the lifespan. This is based on the idea that a combination of environmental,
lifestyle, and genetic factors trigger the onset of AD dementia in the majority of individuals as they age but
“exceptional agers” are protected. To translate this knowledge to design successful personalized prevention
and treatment trials, it is important to identify the parsimonious set(s) of protective factors and how certain
individuals are able to outperform the average population trajectories, i.e., “exceptionally age”. Our central
hypothesis is that each individual's trajectory of amyloid, tau, and cognition will deviate from the average
population trajectories, depending on the individual's genomic variation, lifestyle enrichment, and vascular
health. The aim of this proposal is to apply the unified theoretical framework proposed here to identify
important protective factors against ADP and cognitive decline in a population-based sample and move
towards personalized medicine by discovering paths to “exceptional aging” using two independent
mathematical models (association rule mining and structural equation models).
We will utilize the existing infrastructure of the population-based, longitudinal Mayo Clinic Study of
Aging (MCSA) (individuals aged 60-90 years) which collects imaging surrogates of amyloid (PiB PET) and tau
(tau PET), neuropsychological exams, lifestyle enrichment (midlife cognitive and physical activity), and APOE
gene status. We will also utilize the Rochester Epidemiology Project (REP) which maintains a comprehensive
medical records-linkage system (since 1965), to abstract additional information from the electronic medical
records: longitudinal lab tests (lipid panel), blood pressure, medications, BMI, and diagnosis of cardiac and
metabolic conditions (CMCs) up to 20 years before the amyloid and tau scans. Lastly, we will add a
comprehensive screen of genetic variation related to ADP, related neurodegenerative disorders, and aging
with the latest SNP-based array (NeuroX2).
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科研奖励(0)
会议论文
Investigating Resistance and Resilience Mechanisms in Alzheimer’s Disease
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批准号:10605784
-
项目类别:
-
资助金额:$81.03万
-
财政年份:2017
-
负责人:PRASHANTHI VEMURI
-
依托单位:
Development, Validation, and Application of an Imaging based CVD Scale
-
批准号:9156582
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项目类别:
-
资助金额:$53.86万
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财政年份:2016
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负责人:PRASHANTHI VEMURI
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依托单位:
Development, Validation, and Application of an Imaging based CVD Scale
-
批准号:9335998
-
项目类别:
-
资助金额:$53.86万
-
财政年份:2016
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负责人:PRASHANTHI VEMURI
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依托单位:
Project 1
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批准号:8676251
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项目类别:
-
资助金额:$19.5万
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财政年份:2014
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负责人:PRASHANTHI VEMURI
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依托单位:
HOW DOES RESERVE MODIFY LINKS BETWEEN COGNITION & IMAGING INDICES OF AD PATHOLOGY
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批准号:8733238
-
项目类别:
-
资助金额:$24.9万
-
财政年份:2013
-
负责人:PRASHANTHI VEMURI
-
依托单位:
HOW DOES RESERVE MODIFY LINKS BETWEEN COGNITION & IMAGING INDICES OF AD PATHOLOGY
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批准号:8880085
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项目类别:
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资助金额:$24.15万
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财政年份:2013
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负责人:PRASHANTHI VEMURI
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依托单位:
HOW DOES RESERVE MODIFY LINKS BETWEEN COGNITION & IMAGING INDICES OF AD PATHOLOGY
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批准号:8189012
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项目类别:
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资助金额:$9.0万
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财政年份:2011
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负责人:PRASHANTHI VEMURI
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依托单位:
HOW DOES RESERVE MODIFY LINKS BETWEEN COGNITION & IMAGING INDICES OF AD PATHOLOGY
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批准号:8324513
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项目类别:
-
资助金额:$8.8万
-
财政年份:2011
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负责人:PRASHANTHI VEMURI
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依托单位:
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