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

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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.