Grant: Operating Grant: Mechanisms in Brain Aging and Dementia

Surgery is now more commonly offered as a treatment option to increasingly older and medically complex patients. After surgery, older people frequently experience acute confusion (postoperative delirium). Moreover, up to 30 out of 100 (i.e., 30%) of them have significant changes of their cognitive abilities, compared to before, 1 year after surgery - which is a greater or faster decline than what one would expect just based on age and concomitant diseases. In a study of 1114 patients, 65 years old or older, having non-heart surgery (NeuroVISION-1 study), 7% had a new silent brain infarct on brain magnetic resonance imaging (MRI) around the time of surgery (i.e., perioperative covert stroke). Cognitive decline at 1 year occurred frequently in those without a covert stroke (29%), but significantly more frequently in those with a covert stroke (42%). Perioperative covert stroke also increased the risk of postoperative delirium. Through what mechanisms surgery is associated with these events, and what patients are at higher or lower risk of these events, remain unclear. We will conduct the NeuroVISION-2 study in Canada and worldwide to answer these questions. The study already received funding to support the enrollment of 1300 patients 65 years old or older undergoing elective non-cardiac surgery, the performance in all of them of a brain MRI, and the collection of continuous data on their vital parameters through a wearable technology for 30 days. We now propose to add blood samples collection before and after their surgery to discover molecules circulating in our blood or blood cells, or genetic signatures (overall defined as biomarkers), that are associated with a higher or lower chance of the occurrence of brain injury short- and long-term after surgery. Biomarkers can help understand the mechanisms of these complications and suggest possible therapeutic solutions; they can also enter clinical practice as routine tests to predict patient risk and individualize care.