The effects of added sugar intake on brain blood flow and hippocampal function in midlife adults

摘要 衰老是阿尔茨海默病(AD)的主要危险因素，AD是最常见的痴呆症形式， 这是美国发病率和死亡率增长最快的原因之一。阿尔茨海默病的危险因素出现 在中年时期，类似于心脑血管疾病。在这方面，加强 大的弹性动脉(即主动脉和颈动脉)和脑低灌注率随着年龄的增长而发生 与年龄相关的认知障碍有关，主要是通过将破坏性压力波传递到 脑血管系统，导致脑血管功能障碍和神经元损伤。中年的影响 不良的生活习惯会进一步加剧大脑上的血管变化，包括摄入 含有大量添加糖的饮食(例如，来自超加工食品中含有大量 果糖)。虽然确切的机制尚不清楚，但高糖饮食与血浆升高有关。 甘油三酯(TGS)，它可能通过一种 涉及全身炎症增加的机制。我们的横截面初步数据表明 血浆TGS与动脉僵硬增加、脑血管功能降低、 记忆得分和海马体完整性降低，海马体是一种对编码和 回忆记忆；然而，这些因素是如何被添加的消耗影响的还不清楚。 加糖。这个项目的目的是建立添加糖之间的因果联系的初步证据 中年成年人的摄入量和对血管和大脑健康的不利变化。我们的中心假设是，过度 补充糖摄入会导致减少和海马体结构和功能，尽管对 动脉通过一种涉及血浆TGS升高和全身性炎症的机制。我们将进行一项 一项随机、单盲、控制喂养的研究，以确定食用低含量饮食的效果 (总能量摄入量的5%)与高(总能量摄入量的25%)添加糖各10天 大弹性动脉僵硬、脑血管功能和海马区结构与功能。预期中的 结果证明，添加糖的摄入量与血管和大脑的减少之间存在因果关系。 通过一种涉及甘油三酯升高和炎症的机制发挥作用。此项目生成的数据 将支持未来NIH R01的一项随机对照试验提案，旨在降低 中年成年人。

ABSTRACT Aging is the primary risk factor for Alzheimer's disease (AD) which is the most common form of dementia and among the fastest growing causes of morbidity and mortality in the United States. The risk factors for AD emerge during midlife and are similar to cardiovascular and cerebrovascular diseases. In this regard, stiffening of the large elastic arteries (i.e., the aorta and carotid arteries) and cerebral hypoperfusion occur with aging and are linked to age-related cognitive impairment, primarily through the transmission of damaging pressure waves to the cerebral vasculature, resulting in cerebrovascular dysfunction and neuronal damage. The impact of midlife vascular changes on the brain are further exacerbated by poor lifestyle habits, including the consumption of a diet that contains high amounts of added sugar (e.g., from ultra-processed foods containing high amounts of fructose). While the exact mechanisms are not known, a high sugar diet is associated with elevated plasma triglycerides (TGs), which may exacerbate age-related arterial dysfunction and memory impairment through a mechanism involving increased systemic inflammation. Our cross-sectional preliminary data suggest that plasma TGs are strongly associated with increased arterial stiffness, reduced cerebrovascular function, lower memory scores and decreased integrity of the hippocampus, a brain structure that is critical for encoding and recalling memories; however, it remains unknown how these factors are influenced by the consumption of added sugars. The purpose of this project is to establish preliminary evidence for a causal link between added sugar intake and adverse changes to vascular and brain health in midlife adults. Our central hypothesis is that excess added sugar intake causes reductions and hippocampal structure and function though adverse changes to arteries via a mechanism involving increased plasma TGs and systemic inflammation. We will conduct a randomized, single-blind, controlled-feeding study to determine the effects of consuming a diet containing low (5% of total energy intake) vs. high (25% of total energy intake) added sugar for 10-days each on measures of large elastic artery stiffness, cerebrovascular function and hippocampal structure and function. The expected outcome is evidence of a causal relation between added sugar intake and reductions in vascular and brain functions through a mechanism involving increased TG's and inflammation. The data generated from this project will support a future NIH R01 proposal for a randomized controlled trial aimed at lowering added sugar intake in mid-life adults.