The Impact of Weight Loss on Alzheimer's Disease Risk in Adults with Down Syndrome

减肥对唐氏综合症成人阿尔茨海默病风险的影响

基本信息

批准号：
10518635
负责人：
Lauren Taylor Ptomey
金额：
$ 55.03万
依托单位：
UNIVERSITY OF KANSAS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-30 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10518635
关键词：
Address Adult Age Age-Years Alzheimer&apos s Disease Alzheimer&apos s disease risk Amyloid beta-42 Antioxidants Behavioral Beverages Biological Markers Body Weight Changes Body Weight decreased Calories Carotenoids Cause of Death Cerebrum Chromosome abnormality Chronic Clinical Clinical Trials Cognition Consumption Counseling DASH diet Data Databases Dementia Development Diet Dietary Intervention Dietary Practices Dietary intake Down Syndrome Education Educational Curriculum Food Food Energy Glial Fibrillary Acidic Protein Goals Health education High Prevalence Impact evaluation Incidence Individual Institutional Review Boards Intake Intellectual functioning disability Intervention Light Macronutrients Nutrition Magnetic Resonance Spectroscopy Manuals Monitor Nerve Degeneration Obesity Outcome Outcome Assessment Overweight Oxidative Stress Participant Pathology Patient Recruitments Phase Physical activity Plasma Population Prevalence Procedures Proteins Randomized Readiness Recommendation Records Skin System Time Training Weight maintenance regimen aging brain arm brain volume clinical trial readiness clinically relevant cognitive function fruits and vegetables high risk improved lifestyle intervention meter multi-component intervention neurofilament pilot trial prevent response saturated fat tau-1 treatment arm

项目摘要

Abstract The prevalence of Down syndrome (DS) or trisomy 21, the most common chromosomal abnormality associated with intellectual disability (ID) has increased from ~50,000 in 1950 to ~250,000 in 2017. Most adults with DS will develop pathology associated with Alzheimer's disease (AD) beginning at ~ 30 years of age. By age 65, the cumulative incidence of dementia exceeds 90% and is the leading cause of death in individuals with DS. High prevalence of obesity (~81%) and the accompanying chronic oxidative stress may be associated with increased risk for AD in adults with DS. The available data from trials in typically developed adults suggests the potential for weight loss achieved through a reduced energy diet and/or consuming a low glycemic load, low saturated fat, high fruit and vegetable (F/V) diet to prevent or delay the development of AD. However, the potential of dietary interventions to prevent or delay AD in adults with DS has not been previously examined. Our group has developed a multi-component intervention which includes a reduced energy enhanced Stop Light Diet (eSLD), individual behavioral counseling/education, and daily self-monitoring that has been shown to achieve clinically relevant weight loss (≥ 5%) and improved diet quality in adults with ID. The eSLD includes daily consumption of 2 portion-controlled entrées (~200 kcal each), 2 low-calorie/high protein shakes (~100 kcal each), a minimum of 5 servings of F/V, and ad-libitum non-caloric beverages. Participants are asked to select additional low energy food, if desired, using the SLD system: green (low energy), yellow (moderate energy), and red (high energy). Results from 2 completed (pilot + DK83539) and 1 on-going trial by our group (DK114121), including 335 adults with ID (78 with DS), have demonstrated improved diet quality and clinically relevant weight loss at both 6 mos. (-6.2%) and 12 mos. (-6.8%) using our multi-component intervention with the eSLD. The proposed 2 phase project (clinical readiness and randomized pilot trial) will evaluate the impact of weight loss and diet intake on factors that may prevent or delay the development of AD in adults with DS including biomarkers, cognitive function, cerebral antioxidants, and brain volume. During the clinical readiness phase, we will complete 10 milestones to prepare for successful administration of the RCT. During the RCT phase, adults with DS and overweight/obesity without dementia (n=81) will be randomized (2:1) to a 12-month multicomponent weight management intervention using a reduced energy eSLD + specific recommendations from the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet or a health education control. We will calculate effect sizes for changes in biomarkers related to AD, cerebral antioxidants and brain volume, and cognitive function in both intervention arms across 12 mos. Additionally, we will assess the independent association of weight loss and changes in dietary intake with changes biomarkers related to AD, cerebral antioxidants and brain volume, and cognitive function

抽象的唐氏综合症 (DS) 或 21 三体症（最常见的染色体异常）的患病率与智力障碍 (ID) 相关的人数已从 1950 年的约 50,000 人增加到 2017 年的约 250,000 人。大多数成年人患有 DS 的人将从 30 岁左右开始出现与阿尔茨海默病 (AD) 相关的病理学。 65岁时，痴呆症累计发病率超过90%，是个人死亡的主要原因肥胖症的高患病率（~81%）和伴随的慢性氧化应激可能与 DS 相关。患有 DS 的成人患 AD 的风险增加来自典型发育成人的试验的可用数据。表明通过减少能量饮食和/或摄入低热量来实现减肥的潜力血糖负荷、低饱和脂肪、高水果和蔬菜 (F/V) 饮食可预防或延缓 AD 的发展。然而，饮食干预对于预防或延缓患有 DS 的成人 AD 的潜力此前尚未被证实。我们的小组开发了一种多成分干预措施，其中包括减少能量。强化停车灯饮食 (eSLD)、个人行为咨询/教育以及日常自我监控已被证明可以在患有智力障碍的成人中实现临床相关的体重减轻（≥ 5%）并改善饮食质量。 eSLD 包括每日消耗 2 份控制份量的主菜（每份约 200 kcal）、2 份低热量/高热量蛋白质奶昔（每份约 100 kcal）、至少 5 份 F/V 以及随意饮用的无热量饮料。如果需要，参与者被要求使用 SLD 系统选择额外的低能量食品：绿色（低能量）能量）、黄色（中等能量）和红色（高能量）来自 2 个已完成的结果（试点 + DK83539）和 1 个。我们小组正在进行的试验（DK114121），包括 335 名患有 ID 的成年人（78 名患有 DS），已经证明使用我们的 6 个月 (-6.2%) 和 12 个月 (-6.8%) 改善饮食质量和临床相关体重减轻。拟议的 2 阶段项目（临床准备和随机化）。试点试验）将评估减肥和饮食摄入对可能预防或延迟疾病发生的因素的影响 DS 成人 AD 的发展，包括生物标志物、认知功能、脑抗氧化剂和大脑在临床准备阶段，我们将完成 10 个里程碑，为成功做好准备。在 RCT 阶段，患有 DS 和超重/肥胖但无痴呆的成年人。 (n=81) 将被随机 (2:1) 接受为期 12 个月的多成分体重管理干预，使用减少能源 eSLD + 地中海 DASH 干预措施的具体建议神经退行性延迟 (MIND) 饮食或健康教育控制我们将计算变化的效果大小。与 AD 相关的生物标志物、脑抗氧化剂和脑容量以及干预中的认知功能此外，我们还将评估体重减轻和体重变化之间的独立关联。饮食摄入量会改变与 AD、脑抗氧化剂和脑容量以及认知相关的生物标志物功能