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：
10706534
负责人：
Lauren Taylor Ptomey
金额：
$ 55.16万
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/10706534
关键词：
Adult Age Age Years Alzheimer&apos s Disease Alzheimer&apos s disease risk Amyloid beta-Protein Antioxidants Behavioral Beverages Biological Markers Body Weight Changes Body Weight decreased Calories Carotenoids Cause of Death Cerebrum Chromosome abnormality Chronic 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 Recommendation Records Skin System Time Training Weight maintenance regimen aging brain arm brain volume clinic ready 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）或三体疾病的患病率是最常见的染色体异常与智力残疾（ID）相关的已从1950年的约50,000增加到2017年的〜250,000。与DS一起，将在约30岁开始发展与阿尔茨海默氏病（AD）相关的病理学。经过 65岁，痴呆症的累积事件超过90％，是个体死亡的主要原因与DS。肥胖症的高患病率（约81％）和参与的慢性氧化应激可能与成人DS的AD风险增加。通常开发成人的试验的可用数据表明通过减少能量饮食和/或消耗低量的减肥潜力血糖负荷，低饱和脂肪，高水果和蔬菜（F/V）饮食，以防止或延迟AD的发展。但是，饮食干预措施预防或延迟DS的AD的潜力尚未是以前检查。我们的小组开发了多组分干预措施，其中包括减少能量增强的停止轻饮食（ESLD），个人行为咨询/教育以及日常自我监控已显示可实现ID成人成人的临床相关体重减轻（≥5％）和饮食质量的提高。 ESLD包括每天消费2部分控制的主菜（每个左右约200 kcal），2个低热量/高蛋白质奶昔（每个均约100 kcal），至少5份F/V和Ad-Libitum非平均床。要求参与者使用SLD系统选择其他低能食品：绿色（低能量），黄色（中等能量）和红色（高能量）。 2个完整的结果（Pilot + DK83539）和1个我们的小组（DK114121）正在进行的试验，包括335名ID成年人（78个带有DS），已证明在6个MO中，改善了饮食质量和临床相关的体重减轻。（-6.2％）和12个月。（-6.8％）使用我们与ESLD的多组分干预。拟议的2期项目（临床准备和随机性试点试验）将评估减肥和饮食摄入量对可能阻止或延迟的因素的影响 DS成年人的AD开发，包括生物标志物，认知功能，脑抗氧化剂和大脑体积。在临床准备阶段，我们将完成10个里程碑，为成功做准备 RCT的管理。在RCT阶段，具有DS和超重/肥胖症的成年人无痴呆症（n = 81）将随机分别（2：1）使用A 减少了来自地中海 - 破坏干预的特定建议的能源ESLD + 神经退行性延迟（思维）饮食或健康教育控制。我们将计算更改的效果大小在与AD相关的生物标志物中双臂穿越12个月。此外，我们将评估体重减轻的独立关联和变化饮食摄入量随着与AD，脑抗氧化剂和大脑体积以及认知相关的生物标志物的变化功能