Creatine Intervention in Older Adults to Improve Perioperative Brain Health: a Randomized Controlled Trial (CREATE Trial)

Surgical interventions, while often necessary, are associated with substantial postoperative morbidity, particularly among older adults. Perioperative neurocognitive disorders (PND), characterized by changes in memory patterns in the perioperative period, are among the most common surgical complications in aging populations. Beyond their considerable economic burden, estimated to exceed $30 billion annually, PND imposes profound immediate consequences for patients and caregivers and is associated with long-term adverse outcomes, including an increased risk of dementia. Despite their high prevalence and clinical impact, effective, scalable, and easily implementable preventive strategies for PND remain limited.

Creatine plays a critical role in supporting the brain's high metabolic demands, and its homeostasis may be disrupted during periods of physiological stress such as anesthesia and surgery. Creatine supplementation has been demonstrated to be neuroprotective in high-stress conditions. However, the potential effects of creatine during perioperative cognitive vulnerability have not been previously investigated. This study will evaluate the feasibility of creatine supplementation in the perioperative period and explore its effects on cognitive function and physiological responses to surgery in older adults.