Effect of Bariatric Surgery in Pediatric Obesity on Brain and Cognition

小儿肥胖症减肥手术对大脑和认知的影响

• 批准号: 9111259
• 负责人: Eleanor Race Mackey
• 金额: $ 24.55万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2016-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9111259
• 关键词: 21 year old; Address; Adolescence; Adolescent; Adopted; Adult; Affect; Age; American Heart Association; Animals; Area; Association Learning; Basal Ganglia; Behavior; Blood Pressure; Body Weight decreased; Body mass index; Brain; Cardiovascular Diseases; Cardiovascular system; Categories; Centers for Disease Control and Prevention (U.S.); Child; Childhood; Cognition; Cognitive; Cognitive deficits; Control Groups; Corpus striatum structure; Cues; Data; Decision Making; Development; Discrimination; Eating; Eating Behavior; Face; Fasting; Food; Functional Magnetic Resonance Imaging; Future; Gastrectomy; Gender; Glucose; Health; High Density Lipoproteins; Hippocampus (Brain); Homeostasis; Impaired cognition; Individual; Inflammation; Insulin; Insulin Resistance; Insurance; Intake; Intervention; Malignant Neoplasms; Measurement; Measures; Medial; Mediating; Medical center; Memory; Mental Depression; Metabolic; Metabolic Diseases; Metabolism; Modeling; Morbid Obesity; Musculoskeletal; Neurocognitive; Neurophysiology - biologic function; Non obese; Obesity; Operative Surgical Procedures; Outcome; Paper; Persons; Prefrontal Cortex; Psyche structure; Quality of life; Regulation; Relative (related person); Rest; Rewards; Risk; Short-Term Memory; Source; Stimulus; Temporal Lobe; Testing; Time; United States; Ursidae Family; Ventral Striatum; Waiting Lists; Work; Youth; aged; bariatric surgery; base; cardiovascular health; cognitive function; cognitive testing; cohort; computerized; contextual factors; critical period; disorder risk; economic cost; executive function; feeding; flexibility; frontal lobe; healthy weight; high risk; imaging probe; improved; improved functioning; indexing; lipoprotein triglyceride; long term memory; memory encoding; mortality; neural correlate; obesity in children; obesity prevention; psychologic; psychological outcomes; psychosocial; relating to nervous system; respiratory; saturated fat; self esteem; social; success; visual memory

 DESCRIPTION (provided by applicant): The purpose of this exploratory proposal is to examine effects of bariatric surgery, specifically vertical sleeve gastrectomy, on functional and structural neural and cognitive function in adolescents aged 14-21 years. While obese adults face serious risk of poor health outcomes (cardiovascular, metabolic, musculoskeletal, respiratory, cancer), obese children bear the added burden of poor academic and psychosocial functioning, setting them on maladaptive developmental trajectories resulting in high social and economic costs to the person and the nation. Adolescence is a critical period for maturation of executive and motivational functioning, and severe obesity during this period puts youth at far greater risk for poor physical and psychological outcomes. Bariatric surgery as a treatment option is increasingly being adopted, with proven weight loss (13%-68% excess weight loss in 3-12 months post-surgery in our cohort) and improved metabolic and cardiovascular health. Whether cognitive and brain health also improve is an open question. The proposal will address this gap by taking advantage of the opportunity presented by adolescents who are already undergoing bariatric surgery at Children's National Medical Center. The proposal focuses on three areas of function known to be affected in pediatric obesity: executive function that depends on prefrontal cortes, long-term memory that depends on hippocampus and surrounding regions (medial temporal lobe), and reward function associated with ventral striatum. Aim 1 will test the hypothesis that executive function, verbal and visual memory, and reward sensitivity will improve following surgery. Aim 2 will test the hypothesis that functional activation and connectivity of prefrontal, medial temporal lobe, and ventral striatal regions will improve following surgery, using functional magnetic resonance imaging (fMRI). Lastly, Aim 3 will explore whether the magnitude of weight-loss induced change in metabolic indices (e.g., insulin resistance) mediates association between changes in neural correlates and cognitive function. Fifty adolescents who are candidates for surgery will undergo testing twice, 25 at a minimum of one month before surgery and then again 4 months after surgery, and 25 who have had their surgery delayed for insurance or other reasons who will be tested twice 4-5 months apart; in addition a non-obese control group of 25 adolescents matched for age and gender will also be tested twice at the same intervals. While Aim 1 and 2 seek initial evidence for impact of rapid weight loss on brain and cognitive function, Aim 3 will generate hypotheses about potential metabolic sources of functional neural effects of weight loss to be tested in future work. These findings will further understanding of the influence of the gut on brain and cognition at a critica time in development, by providing neurocognitive markers sensitive to metabolic health that can be used to test mechanistic hypotheses in future work.

 描述（由申请人提供）：本探索性提案的目的是研究减肥手术（特别是垂直袖状胃切除术）对 14-21 岁青少年功能性和结构性神经和认知功能的影响，而肥胖成年人面临严重的贫困风险。健康结果（心血管、代谢、肌肉骨骼、呼吸系统、癌症），肥胖儿童承受着学业和心理社会功能不佳的额外负担，使他们处于适应不良的发展轨迹，从而导致青春期是执行和动机功能成熟的关键时期，这一时期的严重肥胖使青少年面临更大的身体和心理治疗结果不佳的风险。这种选择越来越多地被采用，事实证明，体重减轻了（我们的队列术后 3-12 个月内体重减轻了 13%-68%），并且改善了代谢和心血管健康，认知和大脑健康是否也得到了改善，这是一个悬而未决的问题。该提案将解决这一差距通过利用已经在儿童国家医疗中心接受减肥手术的青少年提供的机会，该提案重点关注已知会受到儿童肥胖影响的三个功能领域：依赖于前额皮质的执行功能、依赖于前额皮质的长期记忆。取决于海马体和周围区域（内侧颞叶），与腹侧纹状体相关的奖励功能将测试执行功能、语言和视觉记忆以及奖励敏感性将在手术后得到改善的假设。使用功能磁共振成像 (fMRI) 假设前额叶、内侧颞叶和腹侧纹状体区域的功能激活和连接将在手术后得到改善。最后，目标 3 将探讨减肥的程度是否会引起代谢指标的变化。 （例如，胰岛素抵抗）介导神经相关性变化和认知功能之间的关联。 50 名准备接受手术的青少年将接受两次测试，其中至少在手术前 1 个月进行 25 次测试，然后在手术后 4 个月再次进行测试，并且25 名因保险或其他原因而推迟手术的人将间隔 4-5 个月接受两次测试；此外，由 25 名年龄和性别相匹配的青少年组成的非肥胖对照组也将在相同的时间间隔内接受两次测试。 1和2寻求初步证据来证明快速减肥对大脑和认知功能的影响，目标3将产生关于减肥的功能性神经效应的潜在代谢来源的假设，这些假设将在未来的工作中进行测试。这些发现将进一步了解快速减肥的影响。大脑上的肠道和通过提供对代谢健康敏感的神经认知标记，可用于在未来的工作中测试机制假设，从而在发育的关键时刻进行认知。

项目成果

Effects of severe obesity and sleeve gastrectomy on cortical thickness in adolescents.

严重肥胖和袖状胃切除术对青少年皮质厚度的影响。

• 发表时间: 2021-09
• 作者: Rajan, Laya;McKay, Cameron C;Santos Malavé, Gabriel;Pearce, Alaina L;Cherry, J Bradley C;Mackey, Eleanor;Nadler, Evan P;Vaidya, Chandan J
• 通讯作者: Vaidya, Chandan J

Effect of Adolescent Bariatric Surgery on the Brain and Cognition: A Pilot Study.

青少年减肥手术对大脑和认知的影响：一项试点研究。

• 发表时间: 2017-11
• 作者: Pearce, Alaina L;Mackey, Eleanor;Cherry, J Bradley C;Olson, Alexandra;You, Xiaozhen;Magge, Sheela N;Mietus;Nadler, Evan P;Vaidya, Chandan J
• 通讯作者: Vaidya, Chandan J