NEURAL RESPONSE TO INSULIN RESISTANCE TREATMENTS

对胰岛素抵抗治疗的神经反应

• 批准号: 8280762
• 负责人: Jason J Hassenstab
• 金额: $ 16.26万
• 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 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8280762
• 关键词: 2,4-thiazolidinedione; 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; Clinical Trials; 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; cognitive function; 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. PUBLIC HEALTH RELEVANCE: Brain functioning is an important determinant of health outcomes and quality of life, and given the scope of the obesity epidemic in the United States, consideration of treatment effects on brain functioning are essential as the obese population ages. Providing evidence of specific mechanisms that promote improved cognitive abilities and brain heath may help clinicians emphasize behaviors and treatment strategies that reduce risk of more serious disease as patients advance in age.

描述（由申请人提供）：这是指导注重患者的职业发展奖（K23）的申请。该奖项将为申请人提供使用神经影像学和神经心理学方法的肥胖和代谢功能障碍的独立研究所需的高级技能。拟议的研究将使用fMRI，代谢功能的生物标志物和神经心理学测试来检查肥胖和久坐的中年成年人的认知和脑反应变化，接受治疗的胰岛素抵抗治疗。我们将在华盛顿大学医学院的营养和肥胖研究中心参加现有的减肥和肥胖研究中心的现有研究研究。参与者将被随机分配到三个条件之一：1）用口服噻唑烷二酮药物（Pioglitazone）进行六个月的治疗，以提高胰岛素敏感性（n = 25）； 2）六个月的标准化体重减轻干预措施，以减轻8-10％的体重和胰岛素敏感性提高（n = 25）；或3）在6个月的常规饮食和体重维持后，等待名单对照组（n = 25）。在基线和跟进时，所有参与者将完成葡萄糖夹测试，身体成分评估，血液测试，血压检查，全面的心理测定评估，简短的精神病学评估，体育锻炼问卷以及结构和功能性MRI。该研究的目的是：1）确定神经心理学性能是否会随着胰岛素敏感性的提高而改善，2）确定对胰岛素的敏感性是否会导致通过fMRI脑反应衡量的神经效率提高。申请人提出了一项全面的培训计划，将教学教学与既定研究人员相结合；正式的课程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，骑士阿尔茨海默氏病研究中心；并与个人导师一起应用培训经验。具体的培训目标包括神经影像学方法中的高级知识和技能获取，包括基于任务的fMRI，fMRI中的纵向方法以及结构性MRI皮质重建技术。课程和研讨会的参与也将提供高级统计建模方法的培训。其他课程将在营养，代谢，内分泌学，多模式神经影像学和负责任的研究中完成。该提案的总体研究目标是检验以下假设：改善通过减轻体重或噻唑烷二酮治疗实现的胰岛素敏感性，伴随着认知性能和fMRI大脑反应的有益变化。 公共卫生相关性：大脑功能是健康结果和生活质量的重要决定因素，并且鉴于美国肥胖症流行的范围，考虑治疗对脑功能的影响至关重要，因为肥胖人群的年龄至关重要。提供促进认知能力和大脑卫生的特定机制的证据，可以帮助临床医生强调行为和治疗策略，以降低随着患者年龄的发展而降低更严重疾病的风险。