Neural mechanisms of HIV-associated CNS dysfunction despite viral suppression
尽管病毒受到抑制,HIV相关中枢神经系统功能障碍的神经机制
基本信息
- 批准号:10217992
- 负责人:
- 金额:$ 68.76万
- 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:2019-07-24 至 2025-05-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAffectAnteriorAreaAttentionBehaviorBehavioralBindingBrainBrain InjuriesBrain scanCellsChronicCognitiveCognitive TherapyCognitive deficitsCorpus striatum structureCross-Sectional StudiesDataDevelopmentDiffusion Magnetic Resonance ImagingDimensionsEmotionalEventFunctional Magnetic Resonance ImagingFunctional disorderFundingGoalsHIVHIV InfectionsHIV therapyHeterogeneityHippocampus (Brain)ImmunologicsImpairmentIndividualInterventionLateralLeadLearningLinkLongitudinal StudiesMagnetic Resonance ImagingMeasuresMedialMediatingMemoryMental TestsModalityMotor CortexMultimodal ImagingNational Institute of Mental HealthNeurocognitive DeficitNeuroimmuneNeurologicParietal LobeParticipantPatternPerformancePharmaceutical PreparationsPhenotypePlasmaPositron-Emission TomographyPrefrontal CortexProcessProteinsPsyche structurePublic HealthRNA IReportingReproducibilityResearch Domain CriteriaResearch PriorityRestServicesShort-Term MemorySiteStructureSubgroupSystemTestingThe Multicenter AIDS Cohort StudyTimeUnited States National Institutes of HealthVerbal LearningViralVirus SheddingWomanWomen&aposs Interagency HIV Studyantiretroviral therapybasebehavior measurementblood oxygen level dependentbrain circuitrycingulate cortexcognitive controlcognitive performancecognitive testingcohortcomorbidityexecutive functioninnovationlongitudinal analysislongitudinal designmacrophagemathematical modelmonocytemultidisciplinaryneural circuitneuroimagingneuroimaging markerneuroinflammationneuromechanismneurotoxicnovelprecision medicineprocessing speedresponsestem
项目摘要
PROJECT SUMMARY/ABSTRACT
Despite the availability of effective antiretroviral therapies, cognitive deficits persist in HIV-infected (HIV+)
individuals. For example, in the Women's Interagency HIV Study (WIHS), HIV+ virally suppressed (HIV+VS)
women showed neurocognitive impairment (NCI) in verbal learning and memory as well as working memory,
attention and executive function. These domains of cognitive performance relate to the declarative memory and
cognitive control subdomains of the NIMH Research Domain Criteria (RDoC), a framework that has not yet been
leveraged to advance understanding of the mechanisms contributing to patterns of NCI in HIV. There is a strong
scientific premise that HIV-associated brain injury stems from immunological processes, particularly
neuroinflammation, mediated by cells of the monocyte/macrophage lineage. In support of this view, studies by
our team and others demonstrate that NCI in HIV is associated with microglial activation and monocyte activation.
In this proposal, our multidisciplinary team will provide innovation to this line of inquiry by conducting a
longitudinal neuroimaging study that not only uses the RDoC framework but also assesses neuroinflammation.
Building on our cross-sectional neuroimaging studies, we will first use task-based functional magnetic resonance
imaging (fMRI) and resting state fMRI in HIV+VS individuals and HIV-uninfected individuals to identify the neural
circuitry contributing to deficits in declarative memory and cognitive control. Second, we will use positron
emission tomography (PET) to assess HIV-related alterations in chronic neuroinflammation in relation to NCI.
Third, we will computationally integrate the multimodal imaging data in relation to changes in cognitive
performance over time. To achieve our goal, we propose a single-site, longitudinal study in phenotypically well-
characterized HIV+VS (N=100) and HIV- controls (N=50) from the WIHS and Multicenter AIDS Cohort Study
(MACS). Participants will complete neuroimaging assessments (resting state and task-based fMRI, structural
MRI, diffusion-weighted MRI) annually for three years and cognitive assessments every six months over that
same time. The longitudinal design allows an assessment of the reproducibility of key findings over time and the
sensitivity of these neuroimaging measures to changes in cognitive performance. To examine HIV-related
alterations in chronic neuroinflammation, a subset of individuals (total n =42; 24 HIV+VS) will also complete PET
assessments using [11C]DPA-713 (DPA). In keeping with NIH research priorities, after 5 years of potential
funding, the impact of this R01 on the field will be to inform our understanding of the mechanisms linked to
neurological comorbidity and to provide novel, more sensitive neuroimaging biomarkers to guide testing of new
cognitive therapies for HIV+ individuals.
项目总结/文摘
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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PAULINE M MAKI其他文献
PAULINE M MAKI的其他文献
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{{ truncateString('PAULINE M MAKI', 18)}}的其他基金
EFFECTS OF MENOPAUSE TRANSITION ON BRAIN STRUCTURE, FUNCTION, AND COGNITION
更年期过渡对大脑结构、功能和认知的影响
- 批准号:
10283070 - 财政年份:2021
- 资助金额:
$ 68.76万 - 项目类别:
EFFECTS OF MENOPAUSE TRANSITION ON BRAIN STRUCTURE, FUNCTION, AND COGNITION
更年期过渡对大脑结构、功能和认知的影响
- 批准号:
10673908 - 财政年份:2021
- 资助金额:
$ 68.76万 - 项目类别:
Neural mechanisms of HIV-associated CNS dysfunction despite viral suppression
尽管病毒受到抑制,HIV相关中枢神经系统功能障碍的神经机制
- 批准号:
9983174 - 财政年份:2019
- 资助金额:
$ 68.76万 - 项目类别:
Neural mechanisms of HIV-associated CNS dysfunction despite viral suppression
尽管病毒受到抑制,HIV相关中枢神经系统功能障碍的神经机制
- 批准号:
10412029 - 财政年份:2019
- 资助金额:
$ 68.76万 - 项目类别:
Menopausal Vasomotor Symptoms and Brain Aging in Women
女性更年期血管舒缩症状和大脑老化
- 批准号:
9927134 - 财政年份:2016
- 资助金额:
$ 68.76万 - 项目类别:
Menopausal Vasomotor Symptoms and Brain Aging in Women
女性更年期血管舒缩症状和大脑老化
- 批准号:
10654010 - 财政年份:2016
- 资助金额:
$ 68.76万 - 项目类别:
Menopausal Vasomotor Symptoms and Brain Aging in Women
女性更年期血管舒缩症状和大脑老化
- 批准号:
9148629 - 财政年份:2016
- 资助金额:
$ 68.76万 - 项目类别:
The Science of Thermoregulation and Vasomotor Symptoms: Possible New Targets for
体温调节和血管舒缩症状的科学:可能的新目标
- 批准号:
8784849 - 财政年份:2014
- 资助金额:
$ 68.76万 - 项目类别:
Effects of Estradiol & Phytoestrogens on Stress Responsivity
雌二醇的作用
- 批准号:
8274899 - 财政年份:2009
- 资助金额:
$ 68.76万 - 项目类别:
Effects of Estradiol & Phytoestrogens on Stress Responsivity
雌二醇的作用
- 批准号:
8072596 - 财政年份:2009
- 资助金额:
$ 68.76万 - 项目类别:
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