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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

摘要