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

• 批准号: 9980475
• 负责人: WILLIAM G SCHRAGE
• 金额: $ 18.72万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/9980475
• 关键词: Acute; Address; Adolescence; Adolescent; Adolescent obesity; Adult; Affect; Age; American; Area; Attention; Behavioral; Blood Vessels; Brain; Cardiovascular Diseases; Cerebrovascular Circulation; Cerebrovascular Disorders; Cerebrum; Child; Childhood; Clinical; Cognition; Cognition Disorders; Cognitive; Collaborations; Communities; Data; Dementia; Development; Diabetes Mellitus; Disease; Dose; Endocrinologist; Exhibits; Flowers; Foundations; Functional disorder; Goals; Health; Heart Diseases; Human; Impaired cognition; Insulin; Insulin Resistance; Intelligence; Lead; Learning; Life; Link; Literature; Lobe; Magnetic Resonance Imaging; Mediating; Memory; Mental Depression; Metabolic; Metabolic hormone; Metabolic syndrome; Methods; Neurocognition; Neurocognitive; Neurocognitive Deficit; Neurologic; Neuropsychological Tests; Neuropsychology; Obesity; Parietal Lobe; Patients; Perfusion; Phase; Physiological; Play; Population; Populations at Risk; Positioning Attribute; Prediabetes syndrome; Principal Investigator; Protocols documentation; Research; Rest; Risk; Role; Severities; Signal Transduction; Stress; Stroke; Structure; Temporal Lobe; Testing; Vascular blood supply; Vasodilator Agents; White Matter Hyperintensity; adolescent brain development; aging brain; biological adaptation to stress; brain dysfunction; brain health; brain volume; cardiovascular risk factor; cerebrovascular; cerebrovascular health; cerebrovascular imaging; cognitive function; dementia risk; design; early onset; executive function; experience; hypoperfusion; improved; insight; insulin signaling; interdisciplinary collaboration; negative affect; neuroimaging; physiologic stressor; preservation; processing speed; programs; prospective; response; social cognition

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.

项目摘要/摘要 五分之一的美国青少年是肥胖的，其中许多患者表现出一定程度的胰岛素抵抗 （ir）。 IR与脑血管疾病，记忆力减少，注意力和认知有关，但是IR如何 在青少年大脑发育过程中为这些做出贡献尚不清楚。该提议的目的是 研究IR驱动神经认知功能和脑降低的程度和机制 青少年的血流（CBF），大脑不良和脑血管健康的风险升高。我们正在测试 总体假设神经认知能力下降与IR的严重程度有关，大脑灌注的减少，应有 到功能失调的胰岛素信号传导。我们建议研究健康青少年的急性CBF控制（12-18岁） 在一系列IR（排除糖尿病）的范围内，与领导的专家儿童神经心理学家合作 综合测试协议。接下来，两种完整的MRI方法（ASL和相比），以及 挑战CBF的生理压力源将用于测试IR对脑大血管的影响是否 CBF和微血管灌注是区域特异性的，在临时和顶壁爱中产生更大的负面影响。 这些爱是最初要改变的大脑领域，并且参与了注意力，记忆，学习和 认识。最后，这项研究测试了认知下降程度是否与CBF应力反应有关 以及IR的严重程度，以及在多大程度上脑灌注介导了IR驱动的较低认知功能。 这项研究将通过广泛的大脑提供首次对青春期IR的全面研究 神经心理学测试和最先进的MR成像，并利用跨学科合作 在发展神经心理学家，血管生理学家和儿科内分泌学家之间。这些 研究旨在发现IR，神经认知功能和CBF之间的基本关系 这些盛开的青少年大脑。令人兴奋的初步数据支持目标 - 尤其是由 生理胰岛素激增 - 尊重这些发现将成为前瞻性，机械的基础 在该临床上重要的人群中减少IR燃烧并改善大脑和认知健康的研究。