Effect of Brain Blood Flow on Cognition Across Healthy Adulthood

To test whether CBF is a cause of decreased cognition, we will dedifferentiate the age-related differences in CBF between young and old healthy adults using a pharmacological aid (i.e., Indomethacin, a non-steroidal anti-inflammatory drug). The currently-proposed study uses a randomised, single-blind mixed (within and between) design whereby young and older adults will complete cognitive tasks with placebo and Indomethacin treatments. Participants will be asked to attend the laboratory for 1 familiarisation (~1 hour) and 2 testing sessions (~3.5 hours each). The familiarisation session is designed for participants to experience complete instrumentation (i.e., complete equipment set up with all physiological variables measured at semi-recumbent rest for a total of 10 minutes) and practice the cognitive tasks 3 times. Testing sessions will start a minimum of 48 hours after familiarisations. During each testing sessions, and after collection of baseline data, each participant will complete cognitive tasks (measuring reaction time and working memory), and tests of neuro/cerebro-vascular function. Following this, participants will receive two pills; either 1.2 mg/kg of Indomethacin and 50 mg of Simethicone, or a placebo and 50 mg of Simethicone. Simethicone is an anti-flatulence medication that has been used previously to prevent GI upset, a potential side-effect of Indomethacin. These will be administered based on a computer-generated randomised order. Then, after 90 minutes of rest (during which participants are free to work, read, chat, or watch a movie), each participant will undergo a second administration of cognitive and neuro/cerebro-vascular function. A minimum 'wash-out' period of 48 hours will occur between testing sessions. The principal investigator, Professor Cotter, has undertaken multiple studies examining CBF and cerebrovascular function in young and older adults in relation to acute and chronic stressors. This has included PI on a study examining effects of Indomethacin in maximal exercise and in prolonged exercise in ambient heat stress, as well as being CI on studies examining effects of Indomethacin on renal function, CBF and cerebrovascular function with acute and chronic hypoxia. Along with Professor Cotter, PhD Candidate Leena Shoemaker will be delivering the intervention. Within the last 2 years, Ms. Shoemaker has successfully run 3 independent studies using the same primary outcomes and equipment as this trial. Both investigators are First aid certified and familiar with the health and safety requirements for human research of this caliber.