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: 8878247
• 负责人: RONALD A COHEN
• 金额: $ 54.49万
• 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/8878247
• 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; cognitive performance; cognitive testing; 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; 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大脑功能影响的机制，并确定减肥手术和减肥的认知益处是否有助于使用多模式神经影像方法评估的大脑代谢或血流动力学功能的增强。将测试术后改善糖尿病相关胰岛素-血糖紊乱的作用。肥胖已达到流行病的程度，现已成为一个主要的公共卫生问题，导致各种合并症，包括脑部紊乱。越来越多的证据表明，即使没有糖尿病、心血管疾病和中风等合并症，慢性肥胖也可能对大脑产生不利影响。我们之前已经表明，体重指数（BMI）升高与认知功能下降有关。减肥手术越来越多地被用来治疗慢性病态肥胖。除了导致许多患者体重急剧减轻外，减肥手术还会改变全身代谢和血管功能，包括改变胰岛素和葡萄糖代谢。我们的多中心纵向研究的初步结果 减肥手术表明，手术后 12 周，人们的神经认知功能（包括记忆力）得到改善。这些益处持续超过 12 个月，不仅与减轻的体重有关，还与潜在风险因素的变化有关，例如代谢功能的改善和 2 型糖尿病的缓解。神经影像学为大脑结构和功能（例如 FMRI）以及脑病理生理学的变化提供了潜在的强大生物标志物。迄今为止，还没有发表的研究按照本研究中的建议检查减肥手术后神经元、代谢和血管脑的变化。我们的初步神经影像数据表明，FMRI 上的功能性大脑反应增强，动脉自旋标记 (ASL) 上的区域脑血流量增加，以及磁共振波谱 (MRS) 上的脑代谢水平变化。我们假设：1）与肥胖相关的大脑代谢和血流动力学紊乱会对大脑功能产生不利影响（从认知测试和 FMRI 可以看出）； 2）减肥手术后的体重减轻和相关的代谢变化可改善大脑功能； 3) 神经认知和神经元功能 (FMRI) 的增强是由于脑代谢 (MRS) 和血管 (ASL) 功能的改善。糖尿病的缓解预计是造成这些影响的一个因素，尽管这种影响也与改善大脑（MRS）和全身（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设计将用于评估这些神经影像学指标、手术前和手术后以及相对非手术肥胖对照的变化。这些组中肥胖的糖尿病患者和非糖尿病患者的比例相同，这使我们能够测试其影响。通过在减肥手术的背景下检查肥胖和减肥，这项研究利用了强大的自然实验操作，可以为了解肥胖和减肥对大脑的影响提供一个独特的窗口。