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

摘要 唐氏综合征(DS)或21三体最常见的染色体异常的患病率 与智力残疾(ID)相关的人数从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的患者会在大约30岁时开始出现与阿尔茨海默病(AD)相关的病理变化。通过 65岁，痴呆症累积发病率超过90%，是个人死亡的主要原因 使用DS。肥胖率高(~81%)和伴随的慢性氧化应激可能是相关的 在患有DS的成年人中，AD的风险增加。来自典型成年人试验的可用数据 暗示通过减少能量饮食和/或低摄入量来实现减肥的潜力 血糖负荷、低饱和脂肪、高水果蔬菜(F/V)饮食可预防或延缓AD的发展。 然而，饮食干预预防或延缓患有DS的成人AD的潜力是以前没有的 检查过了。我们小组开发了一种多成分干预，包括减少能量 增强的停车灯饮食(ESLD)、个人行为咨询/教育和日常自我监控 已被证明在成人ID患者中实现了临床上相关的体重减轻(≥5%)和改善饮食质量。 ESLD包括每天消耗2份可控主食(每份约200千卡)，2份低热量/高热量食物 蛋白质奶昔(每杯约100千卡)，至少5份F/V，以及即兴无热量饮料。 参与者被要求选择额外的低能量食物，如果需要，使用SLD系统：绿色(低 能量)、黄色(中等能量)和红色(高能)。2个已完成(Pilot+DK83539)和1个的结果 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 改善饮食质量和临床相关的体重减轻都在6个月。(-6.2%)和12个月。(-6.8%)使用我们 ESLD的多组分干预。拟议的2阶段项目(临床准备和随机 试点试验)将评估体重减轻和饮食摄入量对可能防止或推迟 成年DS患者AD的发展包括生物标记物、认知功能、脑抗氧化剂和脑 音量。在临床准备阶段，我们将完成10个里程碑，为成功 RCT的管理。在随机对照试验阶段，患有DS和超重/肥胖的成年人没有痴呆 (n=81)将随机(2：1)接受为期12个月的多组分体重管理干预，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(意念)饮食或健康教育对照。我们将计算更改的影响大小 在与AD相关的生物标志物中，脑内抗氧化剂与脑体积、认知功能均有干预作用 双臂交叉12个月。此外，我们将评估体重减轻和体重变化之间的独立联系 饮食摄入量与AD、脑抗氧化剂和脑体积以及认知相关生物标志物的变化 功能

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