NEURAL RESPONSE TO INSULIN RESISTANCE TREATMENTS

对胰岛素抵抗治疗的神经反应

• 批准号: 8828179
• 负责人: Jason J Hassenstab
• 金额: $ 16.32万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8828179
• 关键词: Adult; Age; Alzheimer' s Disease; Amyloid beta-Protein; Antidiabetic Drugs; Award; Behavior Therapy; Bilateral; Biological Markers; Blood Pressure; Blood Tests; Body Composition; Body Weight decreased; Brain; Brain region; Cardiac; Cardiovascular Diseases; Cognition; Cognitive; Control Groups; Dementia; Diet; Disease; Dorsal; Educational workshop; Endocrinology; Enrollment; Epidemic; Episodic memory; Euglycemic Clamping; Event; Functional Magnetic Resonance Imaging; Functional disorder; Glucose; Glucose Clamp; Goals; Health; Hippocampus (Brain); Hydrocortisone; Individual; Instruction; Insulin; Insulin Resistance; Intervention; K-Series Research Career Programs; Knowledge acquisition; Lateral; Lead; Learning; Left; Magnetic Resonance Imaging; Master' s Degree; Measures; Memory; Mentors; Metabolic; Methodology; Monitor; Neuropsychological Tests; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Oral; Outcome; Overweight; Participant; Patients; Performance; Pharmaceutical Preparations; Pharmacological Treatment; Physical activity; Pioglitazone; Process; Psychometrics; Quality of life; Questionnaires; Randomized; Reaction Time; Regulation; Research; Research Personnel; Risk; Short-Term Memory; Sleep Apnea Syndromes; Statistical Models; System; Techniques; Testing; Thiazolidinediones; Training; United States; Universities; Vasodilation; Waiting Lists; Washington; Weight; Weight Gain; aged; base; clinical investigation; cognitive ability; cognitive function; cognitive performance; cognitive system; college; design; executive function; experience; follow-up; improved; insulin sensitivity; interest; medical schools; memory encoding; middle age; neuroimaging; neuroinflammation; neuropathology; neuropsychological; nutrition; patient oriented; prevent; programs; reconstruction; relating to nervous system; response; responsible research conduct; sedentary; skill acquisition; skills; success; treatment effect; treatment strategy; weight maintenance; white matter

DESCRIPTION (provided by applicant): This is an application for a Mentored Patient-Oriented Career Development Award (K23). This award will provide the Applicant with advanced skills needed to establish an independent program of research in obesity and metabolic dysfunction using neuroimaging and neuropsychological methodologies. The proposed study will use fMRI, biomarkers of metabolic functioning, and neuropsychological tests to examine changes in cognition and brain response in obese and sedentary middle aged adults undergoing treatment for insulin resistance. We will enroll 75 obese participants who are participating in an existing study of weight reduction at the Nutrition and Obesity Research Center at Washington University Medical School. The participants will be randomly assigned to one of three conditions: 1) Six months of treatment with an oral thiazolidinedione medication (pioglitazone) to increase insulin sensitivity (n=25); 2) Six months of a standardized weight reduction intervention to achieve an 8-10% weight reduction and increased insulin sensitivity (n=25); or 3) A wait-list control group following 6 months of usual diet and weight maintenance (n=25). At baseline and follow- up, all participants will complete glucose clamp testing, body composition assessment, blood tests, blood pressure checks, comprehensive psychometric assessment, brief psychiatric assessment, physical activity questionnaires, and structural and functional MRI. The aims of the study are: 1) To determine if neuropsychological performance will improve as a function of increased insulin sensitivity and 2) To determine whether improved sensitivity to insulin will result in increased neural efficiency as measured by fMRI brain response. The Applicant proposes a comprehensive training plan, combining didactic instruction with established researchers; formal coursework including completion of a Master's Degree in Clinical Investigation; participation in several advanced workshops; participation in ongoing seminars at Washington University Medical School including the Nutrition and Obesity Research Seminar, the Knight Alzheimer's Disease Research Center; and applied training experiences with individual mentors. Specific training goals include advanced knowledge and skill acquisition in neuroimaging methodologies, including task-based fMRI, longitudinal approaches in fMRI, and structural MRI cortical reconstruction techniques. Training in advanced statistical modeling methodologies will also be provided by coursework and workshop participation. Additional coursework will be completed in nutrition, metabolism, endocrinology, multimodal neuroimaging, and the responsible conduct of research. The overall research goal of this proposal is to test the hypothesis that improved insulin sensitivity achieved through weight reduction or thiazolidinedione treatment is accompanied by beneficial changes in cognitive performance and fMRI brain response.

描述(申请人提供)：这是一份以病人为导向的职业发展指导奖(K23)的申请书。该奖项将为申请者提供所需的高级技能，以建立一个使用神经成像和神经心理学方法进行肥胖和代谢功能障碍研究的独立项目。这项拟议的研究将使用功能磁共振成像、代谢功能的生物标记物和神经心理学测试来检查肥胖和久坐的中年人在接受胰岛素抵抗治疗时认知和大脑反应的变化。我们将招募75名肥胖参与者，他们参与了华盛顿大学医学院营养与肥胖研究中心现有的一项减肥研究。参与者将被随机分配到三种情况之一：1)口服噻唑烷二酮药物(吡格列酮)6个月以提高胰岛素敏感性(n=25)；2)6个月的标准化减肥干预，以实现8%-10%的体重减轻和提高胰岛素敏感性(n=25)；或3)等待名单对照组(n=25)，在正常饮食和体重维持6个月后进行。在基线和随访时，所有参与者将完成葡萄糖钳试验、身体成分评估、血液测试、血压检查、综合心理测量评估、简要精神评估、体力活动问卷以及结构和功能磁共振成像。这项研究的目的是：1)确定神经心理表现是否会随着胰岛素敏感性的增加而改善；2)确定对胰岛素敏感性的改善是否会导致神经效率的提高，这是通过fMRI大脑反应来衡量的。申请者提出了一个全面的培训计划，将教学指导与现有的研究人员结合起来；正式的课程工作，包括完成临床调查硕士学位；参加几个高级研讨会；参加华盛顿大学医学院正在进行的研讨会，包括营养和肥胖研究研讨会、奈特阿尔茨海默病研究中心；以及与个人导师的应用培训经验。具体的培训目标包括获得神经成像方法的高级知识和技能，包括基于任务的功能磁共振成像、纵向功能磁共振成像方法和结构磁共振皮质重建技术。还将通过课程作业和参加讲习班提供先进统计建模方法方面的培训。此外，还将完成营养学、新陈代谢、内分泌学、多模式神经成像和负责任的研究工作。这项提案的总体研究目标是检验这样一个假设，即通过减肥或噻唑烷二酮治疗获得的胰岛素敏感性改善伴随着认知表现和脑功能磁共振反应的有益变化。