Obesity and Type-2 Diabetes: Bariatric Surgery Effects on Brain Function

肥胖和 2 型糖尿病：减肥手术对脑功能的影响

• 批准号: 8697728
• 负责人: RONALD A COHEN
• 金额: $ 56.31万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-25 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8697728
• 关键词: Accounting; Address; Adult; Affect; Age; American; Area; Attention; Back; Biological Markers; Blood Vessels; Body Weight decreased; Body mass index; Brain; Brain region; Cardiovascular Diseases; Cerebrovascular Circulation; Cerebrum; Choline; Chronic; Clinical Sciences; Cognitive; Cognitive deficits; Comorbidity; Control Groups; Data; Diabetes Mellitus; Disease; Disease remission; Epidemic; Epidemiologic Studies; Executive Dysfunction; Functional disorder; Gastric Bypass; Glucose; Goals; Health; Hippocampus (Brain); Impaired cognition; Inflammation; Inflammatory; Insulin; Learning; Link; Longitudinal Studies; Magnetic Resonance Spectroscopy; Measures; Medial; Mediating; Medical; Metabolic; Methods; Morbid Obesity; Motor; N-acetylaspartate; Neurocognitive; Neurons; Neurophysiology - biologic function; Non obese; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Observational Study; Older Population; Operative Surgical Procedures; Participant; Pathway interactions; Patients; Performance; Perfusion; Play; Polysomnography; Prefrontal Cortex; Public Health; Publishing; Recruitment Activity; Relative (related person); Research; Risk; Risk Factors; Role; Serum; Severities; Short-Term Memory; Sleep Apnea Syndromes; Spin Labels; Statistical Models; Stroke; Structure; Testing; Time; United States National Institutes of Health; Vascular Diseases; Weight; Weight maintenance regimen; bariatric surgery; base; blood oxygenation level dependent response; cognitive function; cohort; cytokine; design; diabetic; effective therapy; experience; glucose metabolism; hemodynamics; human data; improved; indexing; interest; memory encoding; memory recall; myoinositol; nervous system disorder; neuroimaging; neurotoxic; non-diabetic; prevent; processing speed; prospective; public health relevance; response; visual memory

DESCRIPTION (provided by applicant): The proposed study will delineate mechanism underlying the effects of chronic obesity on brain functioning and determine if cognitive benefits of bariatric surgery and weight loss contribute to enhanced cerebral metabolic or hemodynamic function assessed using multimodal neuroimaging methods. The contribution of post-surgical improvements in diabetes-associated insulin-glucose disturbances will be tested. Obesity has reached epidemic proportions and is now a major public health problem, contributing to various comorbid medical conditions, including brain disturbances. There is increasing evidence that chronic obesity may adversely affect the brain, even in the absence of comorbid diseases, such as diabetes, cardiovascular disease, and stroke. We have previously shown that elevated body mass index (BMI) is associated with reduced cognitive function. Increasingly, bariatric surgery is being used as a treatment for chronic morbid obesity. Besides causing dramatic weight loss in many patients, bariatric surgery alters systemic metabolic and vascular function, including altering insulin and glucose metabolism. Our initial findings from a multicenter longitudinal study of bariatric surgery indicated that people experience improvements in neurocognitive functioning, including memory recall, by 12 weeks post-surgery. These benefits continue over 12 months and are related not only to the amount of weight lost, but also changes in underlying risk factors, such as improved metabolic function, and remission of type-2 diabetes Neuroimaging provides a potentially powerful biomarker of alterations in brain structure and function (e.g., FMRI), as well as cerebral pathophysiology. To date no published studies have examined neuronal, metabolic and vascular brain changes following bariatric surgery as proposed in this study. Our preliminary neuroimaging data indicates enhanced functional brain response on FMRI, increased regional cerebral blood flow on arterial spin labeling (ASL), and changes in cerebral metabolite levels on magnetic resonance spectroscopy (MRS). We hypothesize that: 1) Cerebral metabolic and hemodynamic disturbances linked to obesity adversely affect brain function (evident from cognitive testing and FMRI); 2) Weight loss and associated metabolic changes post-bariatric surgery improve brain functions; and 3) Enhanced neurocognitive and neuronal function (FMRI) are due to improved cerebral metabolic (MRS) and vascular (ASL) function. Remission of diabetes is expected to be one factor accounting for these effects, though this effect will also be tied to improved cerebral (MRS) and systemic (e.g., serum cytokines) metabolic health and cerebral perfusion (ASL). A prospective longitudinal cohort matched design will be used to assess changes in these neuroimaging indices, pre- and post-surgery and relative non-surgical obese controls. The groups will have equal proportions of diabetics and non-diabetics with obesity, enabling us to test its influence. By examining obesity and weight loss in the context of bariatric surgery, this study capitalizes on a powerful natural experimental manipulation that can provide a unique window into the effects of obesity and weight loss on the brain.

描述（由申请人提供）：拟议的研究将描述慢性肥胖对脑功能的影响的基础机制，并确定减肥手术和体重减轻的认知益处是否有助于增强使用多模式神经模仿方法评估的大脑代谢或血液动力学功能。将测试与糖尿病相关胰岛素 - 葡萄糖疾病的手术后改善的贡献。肥胖已经达到了流行病的比例，现在是一个重大的公共卫生问题，导致了各种合并症，包括脑部障碍。越来越多的证据表明，即使在没有合并症的情况下，慢性肥胖可能会对大脑产生不利影响，例如糖尿病，心血管疾病和中风。我们以前已经表明，体重指数升高（BMI）与认知功能降低有关。减肥手术越来越多地用作慢性病肥胖症的治疗方法。除了引起许多患者的急剧体重减轻外，减肥手术还改变了全身代谢和血管功能，包括改变胰岛素和葡萄糖代谢。我们来自多中心纵向研究的最初发现 减肥手术表明，在手术后12周之前，人们在神经认知功能（包括记忆召回）方面有所改善。这些好处持续了12个月，不仅与减轻体重的量相关，而且还与潜在危险因素的变化有关，例如改善代谢功能，以及2型糖尿病神经影像学的减轻提供了潜在的强大生物标记大脑结构和功能改变的生物标志物（例如FMRI），以及脑病病理生理学。迄今为止，尚无公开的研究研究在本研究中提出的减肥手术后的神经元，代谢和血管大脑的变化。我们的初步神经影像学数据表明在fMRI上的功能性大脑反应增强，动脉自旋标记（ASL）上的区域脑血流增加，以及磁共振光谱（MRS）上脑代谢物水平的变化。我们假设：1）与肥胖有关的大脑代谢和血液动力学障碍对脑功能有不利影响（从认知测试和fMRI中看出）； 2）体重减轻和相关的代谢变化后手术后手术改善了大脑功能； 3）增强的神经认知和神经元功能（fMRI）是由于改善的脑代谢（MRS）和血管（ASL）功能引起的。糖尿病的缓解预计将是这些影响的因素之一，尽管这种作用也将与改善大脑（MRS）和全身性（例如血清细胞因子）代谢健康和脑灌注（ASL）有关。前瞻性纵向队列匹配的设计将用于评估这些神经影像学指数，手术前后和相对非手术肥胖对照的变化。这些群体将具有与肥胖症相同的糖尿病患者和非糖尿病患者的比例，从而使我们能够测试其影响。通过检查减肥手术背景下的肥胖和体重减轻，这项研究利用了强大的自然实验操作，可以为肥胖和体重减轻对大脑的影响提供独特的窗口。