Utility of Centrally Acting Angiotensin Converting Enzyme Inhibitors to slow the progression of Dementia
中枢作用血管紧张素转换酶抑制剂减缓痴呆进展的效用
基本信息
- 批准号:10259832
- 负责人:
- 金额:$ 16万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-15 至 2025-05-31
- 项目状态:未结题
- 来源:
- 关键词:AcetylcholineAddressAffectAgingAlzheimer&aposs DiseaseAlzheimer&aposs disease riskAngiotensin IIAngiotensin-Converting Enzyme InhibitorsAttentionAwardBiologicalBiometryBlood - brain barrier anatomyBlood PressureBlood VesselsBrainCerebrovascular CirculationClinicalClinical MarkersCognitionCognitiveConsumptionCoupledDataDatabasesDementiaDetectionDevelopmentDiabetes MellitusDiseaseDrug PrescriptionsEarly identificationElderlyEpidemiologic MethodsGaitGoalsGrantHarm ReductionHealth and Retirement StudyHeart failureHypertensionImpaired cognitionIncidenceIndividualInflammatoryInvestigationKidneyKidney DiseasesKnowledgeLacunar InfarctionsLearningLinkMemoryMemory impairmentMentored Patient-Oriented Research Career Development AwardMicrovascular DysfunctionModalityMotorNerve DegenerationNeurobiologyNeuronsNeuropsychological TestsObservational StudyOutcomeParticipantPathologicPathologyPathway interactionsPeripheralPharmaceutical PreparationsPhysical PerformancePhysiciansPopulationPrevalencePreventionRegistriesRenin-Angiotensin SystemResearchResearch PersonnelResearch TrainingRiskRoleStructureSystemTechniquesTestingTimeTrainingWhite Matter DiseaseWorkbasecareercareer developmentclinically relevantcognitive developmentcohortcytokinedementia riskdesignevidence baseexecutive functionexperiencefallsfunctional declinehippocampal atrophyimprovedlongitudinal analysismemory consolidationmemory retrievalmild cognitive impairmentneural correlateneuroimagingneuropathologyrate of changeskillstargeted treatment
项目摘要
Abstract
My prior training, background, and experiences are very relevant to my specific plans as described in the grant.
My overall career development goal is to develop the skills necessary to pursue a career as an independent
clinical researcher, able to conduct investigations that will broaden our understanding of the relationship
between functional decline in aging and medication use.
My specific research training objectives during the 5-year award period are: 1. To enhance my knowledge
of neural correlates of gait and cognitive dysfunction. 2. Advance my knowledge of the brain Renin
Angiotensin System (RAS) and connected pathways as a biological pathway that may link cognitive and
motoric declines in aging. 3. Learn neuroimaging modalities and analytic techniques to identify and quantify
structural findings related to cognitive and functional decline in aging. 4. Improve my knowledge of
epidemiological methods and biostatistics for observational studies and longitudinal analysis. 5. Apply for an
ROI grant at the end of this K23 award to extend this line of research into additional cohorts that will allow for
more detailed investigations into the use of CACE-I and related agents in protecting against declines in gait
and cognition in older adults at risk for Alzheimer’s disease and related disorders.
My research aims will add to our knowledge of the clinical and neurobiological consequences of medication
use in aging by focusing on medications with less of a negative impact on functional decline than similar
medication counterparts. Angiotensin Converting Enzyme Inhibitors (ACEI) are widely used for a number of
conditions beyond hypertension. They can be categorized as centrally or peripherally acting based upon their
ability to cross the blood brain barrier. Available data suggests that centrally acting ACEI decrease the rate of
cognitive and functional decline among those with Alzheimer’s Disease and related disorders. My specific
aims focus on older individuals without Alzheimer’s disease and related disorders and are to 1) To
quantify motoric consequences (gait velocity) of CACE-I versus PACE-I use in older adults using the nationally
representative Health and Retirement Study (HRS) database. 2) To determine cognitive consequences of
CACE-I versus PACE-I use in older adults using the HRS. 3) To examine the relation of CACE-I and PACE-I
use with neurodegenerative and vascular pathologies linked to dementia using the Alzheimer’s disease
Neuroimaging Initiative (ADNI) database.
Early identification of older adults at risk for the development of cognitive impairment and decline in physical
performance, coupled with a better understanding of how ACEI subtypes affect cortical regions associated with
dementia, is of paramount importance as a prelude to identification of targeted therapies to slow the
progression of cognitive impairment in aging and Alzheimer’s Disease. There is a knowledge gap regarding
clinical consequences of different classes of ACEI that limits evidence based prescribing. This proposal will
produce clinically relevant data that will form the basis of an R01 designed to extend this line of research into
additional cohorts, to allow for more detailed investigations into the use of CACE-I and related agents in
protecting against declines in gait and cognition in older adults at risk for Alzheimer’s disease and related
disorders.
摘要
我之前的培训,背景和经验与我在资助中描述的具体计划非常相关。
我的总体职业发展目标是发展必要的技能,以追求作为一个独立的职业生涯
临床研究人员,能够进行调查,这将扩大我们对关系的理解
与药物使用之间的联系
我在5年获奖期间的具体研究培训目标是:1。为了增进我的知识
步态和认知功能障碍的神经相关性。2.增进我对大脑的了解
血管紧张素系统(RAS)和相关通路作为一种生物学通路,可能将认知和
运动能力下降3.学习神经成像模式和分析技术,以识别和量化
结构发现与认知和功能衰退的老龄化。4.提高我的知识
观察性研究和纵向分析的流行病学方法和生物统计学。5.申请
在K23奖结束时的ROI赠款,将这一系列研究扩展到其他队列,
对CACE-I和相关药物在防止步态下降中的应用进行了更详细的研究
和认知能力的研究。
我的研究目标将增加我们对药物治疗的临床和神经生物学后果的认识
通过专注于对功能衰退的负面影响小于类似药物的药物,
药物对应。血管紧张素转化酶抑制剂(ACEI)广泛用于许多治疗。
高血压以外的疾病它们可以被分类为中心或外围作用的基础上,其
穿越血脑屏障的能力。现有的数据表明,中枢作用的ACEI降低了
认知和功能下降与阿尔茨海默病和相关疾病。我的具体
目标集中在老年人没有阿尔茨海默病和相关疾病,并1)
使用全国范围内的标准,量化CACE-I与PACE-I在老年人中使用的运动后果(步态速度)
健康与退休研究(HRS)数据库。2)为了确定认知后果
CACE-I与PACE-I在使用HRS的老年人中的使用。3)检查CACE-I和PACE-I的关系
用于与阿尔茨海默病痴呆相关的神经变性和血管病变
神经影像学倡议(ADNI)数据库。
早期识别有认知障碍和身体机能下降风险的老年人
性能,再加上更好地了解ACEI亚型如何影响与
痴呆症,是至关重要的,作为一个前奏,以确定有针对性的治疗,以减缓
老年认知障碍和阿尔茨海默病的进展。在以下方面存在知识差距:
不同类别ACEI的临床后果限制了循证处方。这项建议会
产生临床相关数据,这些数据将构成R 01的基础,R 01旨在将这一研究领域扩展到
额外的队列,以便更详细地研究CACE-I和相关药物的使用,
防止有阿尔茨海默病及相关疾病风险的老年人步态和认知能力下降
紊乱
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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Claudene George其他文献
Claudene George的其他文献
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{{ truncateString('Claudene George', 18)}}的其他基金
Utility of Centrally Acting Angiotensin Converting Enzyme Inhibitors to slow the progression of Dementia
中枢作用血管紧张素转换酶抑制剂减缓痴呆进展的效用
- 批准号:
10642850 - 财政年份:2020
- 资助金额:
$ 16万 - 项目类别:
Utility of Centrally Acting Angiotensin Converting Enzyme Inhibitors to slow the progression of Dementia
中枢作用血管紧张素转换酶抑制剂减缓痴呆进展的效用
- 批准号:
10408178 - 财政年份:2020
- 资助金额:
$ 16万 - 项目类别:
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