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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：
WILLIAM G SCHRAGE
金额：
$ 18.72万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
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

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

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