Novel food-based approach for prevention of age-associated cognitive decline inolder adults with obesity

超重和肥胖的老年人容易出现认知能力下降，患痴呆症的风险是前者的两倍。 与没有超重或肥胖的成年人相比，他们患有阿尔茨海默氏症。然而，关于营养的研究 支持认知健康的干预措施一直是支离破碎的，很大程度上局限于测试个人营养 因素或一般健康的饮食模式。这项提案的首要目标是响应PAR-18-877， 是确定有效的基于营养的干预措施来改善老年人的认知和脑功能 超重和肥胖。我们的中心假设是年龄敏感的认知功能和脑血流 (脑血流量，脑健康的一个重要生物标志物)在超重或 食用新型多组分营养补充剂(MCNS)导致的肥胖 结合行为减肥(WL)干预。科学的前提是老年人有 超重和肥胖会继发于超重损害大脑的病理生理变化。 大脑的结构和功能，因此特别容易受到营养缺乏和氧化的影响 因此，认知健康的最佳营养干预应该提供一个全面的小组 营养和其他食物成分，支持结构和功能重塑，同时减少炎症 和氧化损伤。该项目是由一个多学科团队提出的，该团队在 研究。这项工作的概念基础得到了我们最近令人信服的数据支持 MCNS对改善幼儿执行功能和脑血流的疗效 里程碑式的进步，因为不太全面的补充剂配方被发现无效。 一项为期一年的随机安慰剂对照试验将在268名超重和 肥胖，目标营养素摄入量低，认知正常或轻度认知障碍。2x2析因设计 将参与者随机分为：i)含有包括表儿茶素和儿茶素的黄烷醇的MCNS补充剂， 必需的微量营养素和omega-3脂肪酸，或等卡路里安慰剂；以及b)接受行为WL 干预或注意控制。主要结果将是综合认知z分数的变化 在5项神经心理测试上有良好的标准化分数。我们假设认知能力得到改善 与对照组相比，随机分为MCNS、WL和MCNS+WL的参与者的功能，平均值最高 MCNS+WL参与者的好处。主要的分析是意向治疗。线性混合效应模型将 用于评估MCNS、WL和MCNS+WL与对照组以及MCNS+WL与MCNS和WL的效果 独自一人。对于其他可靠的来源和微血管脑血流，将进行额外的认知测试 和大血管脑血流速度将使用漫相关光谱和 经颅多普勒超声。这项研究将确定基于营养的实用干预措施，以改善 促进弱势老年人的认知健康，以支持公共卫生倡议的转型进展。

Older adults with overweight and obesity are vulnerable cognitive decline, and have twice the risk of dementia and Alzheimer's Disease compared to adults without overweight or obesity. However, research on nutritional interventions to support cognitive health has been fragmented, and largely restricted to testing individual nutrition factors or generally healthy dietary patterns. The overarching goal of this proposal, responding to PAR-18-877, is to identify effective nutrition-based interventions to improve cognitive and brain functioning in older adults with overweight and obesity. Our central hypothesis is that age-sensitive cognitive functions and cerebral blood flow (CBF, an important biomarker of brain health) can be significantly increased in older adults with overweight or obesity by consumption of a novel multiple-component nutrition supplement (MCNS) used alone or in combination with a behavioral weight loss (WL) intervention. The scientific premise is that older adults with overweight and obesity have pathophysiological changes in the brain secondary to excess weight that damage brain structure and function, and as a result are particularly susceptible to nutritional deficiencies and oxidative stress; thus, optimal nutritional interventions for cognitive health should provide a comprehensive panel of nutrients and other food constituents to support structural and functional remodeling while reducing inflammation and oxidative damage. The project is proposed by a multidisciplinary team with expertise in all aspects of the research. The conceptual basis of the work is supported by our recent compelling data demonstrating effectiveness of a MCNS for improving executive function and cerebral blood flow in young children, which is a landmark advance because less comprehensive supplement formulations have been found to be ineffective. A 1-year randomized placebo-controlled trial will be conducted in 268 older adults with overweight and obesity, low intakes of target nutrients, and normal cognition or mild cognitive impairment. A 2x2 factorial design will randomize participants to: i) a MCNS supplement containing flavanols including epicatechin and catechin, essential micronutrients and omega-3 fatty acids, or to an isocaloric placebo; and b) to receive a behavioral WL intervention or an attentional Control. The primary outcome will be change in a composite cognitive z-score of well-established standardized scores on 5 neuropsychological tests. We hypothesize improved cognitive function in participants randomized to MCNS, WL and MCNS+WL compared to Controls, with greatest mean benefits in MCNS+WL participants. The primary analysis is intention-to-treat. Linear mixed-effects models will be applied to assess the effects of MCNS, WL, and MCNS+WL vs. Control and MCNS+WL vs. MCNS and WL alone. Additional cognitive tests will be drawn for other reliable sources, and microvascular cerebral blood flow and macrovascular cerebral blood flow velocity will be measured using diffuse correlation spectroscopy and transcranial Doppler ultrasound. This research will identify practical nutrition-based interventions for improving cognitive health in vulnerable older adults to support transformational advances in public health initiatives.