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）的主要风险因素，阿尔茨海默病是痴呆症的最常见形式， 是美国发病率和死亡率增长最快的原因。AD的风险因素出现 与心脑血管疾病相似。在这方面， 大的弹性动脉（即，主动脉和颈动脉）和脑灌注不足随着年龄的增长而发生， 与年龄相关的认知障碍有关，主要是通过传播破坏性的压力波， 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血管的变化，包括食用 含有大量添加糖的饮食（例如，从超加工食品含有大量的 果糖）。虽然确切的机制尚不清楚，但高糖饮食与血浆水平升高有关 甘油三酯（TG），这可能会加剧年龄相关的动脉功能障碍和记忆障碍，通过 机制涉及增加全身炎症。我们的横向初步数据表明， 血浆TG与动脉僵硬度增加、脑血管功能降低、 记忆分数和海马体的完整性下降，海马体是一种对编码和 然而，仍然不清楚这些因素是如何受到消费的影响。 糖。这个项目的目的是建立一个因果关系的初步证据之间添加糖 摄入量和不利的变化，血管和大脑健康的中年人。我们的核心假设是 添加糖的摄入会导致海马结构和功能的减少， 通过涉及血浆TG增加和全身炎症的机制影响动脉。我们将进行 一项随机、单盲、控制喂养的研究，以确定食用含低剂量的饮食的影响。 （总能量摄入量的5%）与高（总能量摄入量的25%）添加糖各10天， 大动脉弹性刚度、脑血管功能和海马结构与功能。预期 结果是增加糖摄入量和减少血管和大脑之间的因果关系的证据 通过一种机制发挥作用，包括增加甘油三酯和炎症。这个项目产生的数据 将支持未来NIH R01的一项随机对照试验提案，该试验旨在降低 中年人

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.