Thiamine Intervention and Cognition in Older Adults Undergoing Coronary Artery Bypass Grafting- A Randomized Clinical Trial

项目摘要/摘要 冠心病(CHD)是一个常见的健康问题，需要超过230,500名患者接受 在美国，每年都有冠状动脉搭桥术(CABG)。尽管改善的根本目标是 功能、持续时间和生活质量的提高与冠状动脉搭桥术相关。 有害的认知变化，这可能导致早期痴呆症和阿尔茨海默病风险增加 发病率、死亡率、生活质量和社会功能下降。然而，潜在的机制 造成这种缺陷的原因尚不清楚，但可能包括应激诱导的炎性风暴和厌氧症。 活动。高乳酸水平是无氧代谢的指标，在冠状动脉搭桥术和无氧代谢后很常见。 过程可能导致冠状动脉搭桥术后的认知缺陷。无氧代谢活动可通过以下方法减少 输注硫胺素，这是有氧代谢中的一个重要辅助因素。在缺乏足够的硫胺素的情况下 水平，丙酮酸不能进入克雷布斯循环，促进无氧代谢，增加乳酸 制作。然而，目前尚不清楚是否可以使用低成本的硫胺素干预来减少冠状动脉搭桥术后的费用 无氧运动和减少冠心病受试者的认知问题。采用两组、双盲、随机、 纵向研究设计：52例接受冠状动脉搭桥术的冠心病患者(年龄60-80岁，26例接受硫胺素治疗和26例接受硫胺素治疗 安慰剂)将参与对血液中硫胺素、乳酸和炎症的认知评估和评估 标记级别。具体目的是：1)评估硫胺素治疗对血乳酸、硫胺素和 老年冠心病患者基线干预前后的炎症(IL-10、IL-6、IL-1β、肿瘤坏死因子-α)水平 (5天内)和冠状动脉搭桥术后1个月；2)检测硫胺素干预对认知功能的影响，评估 由NIH工具箱认知电池，蒙特利尔认知评估，和广泛的评估 伴与不伴冠心病成人的记忆与学习2及乳酸水平与认知的关系 在基线(5天内)和冠状动脉搭桥术后1个月内进行治疗；以及3)检查硫胺素输注的效果 冠状动脉旁路移植术对老年冠心病患者术后6个月远期认知、生活质量及日常活动状况的影响 接受和不接受治疗的受试者。综上所述，冠脉搭桥术后认知障碍在冠心病患者中很常见。 围手术期发生的无氧代谢活动对认知有害。 补充硫胺素会导致营养不良，并导致痴呆症和阿尔茨海默病的风险，这些风险可以通过注射硫胺素来降低。 硫胺素输注将促进有氧代谢，降低乳酸和炎症水平，并将起到 作为细胞内的蛋白质分解和分解保护剂。这些发现有可能极大地影响 临床实践提供了低成本硫胺素干预的证据，这种干预可以在大范围- 扩大临床试验以减少冠状动脉搭桥术后的认知障碍，从而改善社会功能和 提高生活质量和日常活动，降低老年冠心病患者的早期痴呆症和阿尔茨海默病风险。

PROJECT SUMMARY/ABSTRACT Coronary heart disease (CHD) is a common health issue, requiring over 230,500 patients to undergo coronary artery bypass grafting (CABG) each year in the USA. Despite the fundamental goal of improving function and increasing both duration and quality of life, CABG surgery is associated with increased risk of deleterious cognition changes, which may contribute to early dementia and Alzheimer’s disease risks, increased morbidity, mortality, and decreased quality of life and social function. However, the potential mechanisms contributing to such deficits remain unclear, but may include stress-induced inflammatory storm and anaerobic activities. High lactate levels, indicator of anaerobic metabolism, are common after CABG, and anaerobic processes may contribute to post-CABG cognitive deficits. Anaerobic metabolic activities can be reduced with infusion of thiamine, which is an essential co-factor in aerobic metabolism. In the absence of adequate thiamine levels, pyruvate fails to enter the Krebs cycle, promoting anaerobic metabolism and increasing lactate production. However, it is unclear whether a low-cost thiamine intervention can be used to reduce post-CABG anaerobic activities and reduce cognitive issues in CHD subjects. Using a two-group, double-blind randomized, longitudinal study design, 52 CHD patients undergoing CABG (age, 60-80 years; 26 thiamine treatment and 26 placebo) will participate for cognitive assessment and evaluation of blood thiamine, lactate, and inflammatory marker levels. The specific aims are to: 1) assess thiamine treatment effect on blood lactate, thiamine, and inflammatory (IL-10, IL-6, IL-1β, TNF-α) levels in older CHD subjects with and without intervention at baseline (within 5 days) and one month after CABG; 2) examine the effect of thiamine intervention on cognition, evaluated by the NIH Toolbox Cognition Battery, the Montreal Cognitive Assessment, and the Wide Range Assessment of Memory and Learning 2, and relationships between lactate levels and cognition in CHD adults with and without treatment at baseline (within 5 days) and one month after CABG; and 3) examine the effect of thiamine infusion after CABG on long-term cognition, quality of life, and daily activities status at 6 mo after CABG in older CHD subjects with and without treatment. In summary, post-CABG cognitive deficits are common in CHD patients. Anaerobic metabolic activities that occur during perioperative period, are deleterious introducing cognitive deficits and leading to dementia and Alzheimer’s disease risks that can be reduced with thiamine infusion. Thiamine infusion will promote aerobic metabolism and reduce lactate and inflammatory levels, and will serve as an intracellular proteolysis and breakdown protector. The findings have the potential to dramatically impact clinical practice by offering evidence for a low-cost thiamine intervention that could be implemented on a large- scale clinical trial to reduce post-CABG cognitive deficits, which could consequently improve social function and quality of life and daily activities, and reduce early dementia and Alzheimer’s disease risks in older CHD patients.