Insulin resistance, cognitive health, and perfusion of the adolescent brain

胰岛素抵抗、认知健康和青少年大脑灌注

基本信息

  • 批准号:
    9980475
  • 负责人:
  • 金额:
    $ 18.72万
  • 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:
    2019-08-01 至 2022-07-31
  • 项目状态:
    已结题

项目摘要

Project Summary/Abstract One in five American adolescents are obese, and many of these patients exhibit some level of insulin resistance (IR). IR is associated with cerebrovascular disease, reduced memory, attention, and cognition, but how IR contributes to these in the course of adolescent brain development is unclear. The goal of this proposal is to investigate the extent and mechanisms by which IR drives reductions in neurocognitive function and cerebral blood flow (CBF) in adolescents at elevated risk of poor brain and cerebrovascular health. We are testing the overall hypothesis that neurocognitive decline is linked to severity of IR, as are reductions in brain perfusion, due to dysfunctional insulin signaling. We propose to study acute CBF control in healthy adolescents (12-18 years) across a range of IR (diabetes excluded) in collaboration with expert childhood neuropsychologists who lead a comprehensive testing protocol. Next, two complementary MRI methods (ASL and Phase Contrast), along with a physiologic stressor to challenge CBF, will be used to test whether the impact of IR on brain macrovascular CBF and microvascular perfusion is regionally specific, with more negative effects in temporal and parietal lobes. These lobes are some of the initial brain areas to change, and are involved in attention, memory, learning, and cognition. Finally, this study tests whether the degree of cognitive decline is linked to the CBF stress response and to severity of IR, and to what extent brain hypoperfusion mediates the IR-driven lower cognitive function. This study will provide the first comprehensive look at IR in adolescent brains, by utilizing extensive neuropsychological testing and state-of-the-art MR imaging, and drawing on interdisciplinary collaborations between developmental neuropsychologists, vascular physiologists, and pediatric endocrinologists. These studies are designed to uncover fundamental relationships between IR, neurocognitive function, and CBF in these blossoming adolescent brains. Exciting preliminary data support the aims—particularly uncovered by a physiologic insulin surge—signifying these findings will serve as a foundation for prospective, mechanistic studies to reduce the burden of IR and improve brain and cognitive health in this clinically important population.
项目总结/文摘

项目成果

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WILLIAM G SCHRAGE其他文献

WILLIAM G SCHRAGE的其他文献

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{{ truncateString('WILLIAM G SCHRAGE', 18)}}的其他基金

Human cerebral blood flow regulation: sex, mechanism, and stress differences
人类脑血流调节:性别、机制和应激差异
  • 批准号:
    10650368
  • 财政年份:
    2020
  • 资助金额:
    $ 18.72万
  • 项目类别:
Human cerebral blood flow regulation: sex, mechanism, and stress differences
人类脑血流调节:性别、机制和应激差异
  • 批准号:
    10407466
  • 财政年份:
    2020
  • 资助金额:
    $ 18.72万
  • 项目类别:
Peripheral Vasodilation in Obese Humans
肥胖人群的外周血管舒张
  • 批准号:
    8185406
  • 财政年份:
    2011
  • 资助金额:
    $ 18.72万
  • 项目类别:
Peripheral Vasodilation in Obese Humans
肥胖人群的外周血管舒张
  • 批准号:
    8515512
  • 财政年份:
    2011
  • 资助金额:
    $ 18.72万
  • 项目类别:
Peripheral Vasodilation in Obese Humans
肥胖人群的外周血管舒张
  • 批准号:
    8688332
  • 财政年份:
    2011
  • 资助金额:
    $ 18.72万
  • 项目类别:
Peripheral Vasodilation in Obese Humans
肥胖人群的外周血管舒张
  • 批准号:
    8323220
  • 财政年份:
    2011
  • 资助金额:
    $ 18.72万
  • 项目类别:
Aging and Microvascular Dysfunction in Human Skeletal Muscle
人体骨骼肌的衰老和微血管功能障碍
  • 批准号:
    7587863
  • 财政年份:
    2009
  • 资助金额:
    $ 18.72万
  • 项目类别:
Aging and Microvascular Dysfunction in Human Skeletal Muscle
人体骨骼肌的衰老和微血管功能障碍
  • 批准号:
    7770776
  • 财政年份:
    2009
  • 资助金额:
    $ 18.72万
  • 项目类别:
Muscle Pump and Chemical Dilation in Exercise Hyperemia
运动充血中的肌肉泵和化学扩张
  • 批准号:
    6710162
  • 财政年份:
    2002
  • 资助金额:
    $ 18.72万
  • 项目类别:
Muscle Pump and Chemical Dilation in Exercise Hyperemia
运动充血中的肌肉泵和化学扩张
  • 批准号:
    6447034
  • 财政年份:
    2002
  • 资助金额:
    $ 18.72万
  • 项目类别:

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