Cognitive Outcomes and Neuroimages Associated With Anesthesia-Related EEG Signatures

In 1955 Bedford reported the "adverse cerebral effects of anesthesia on old people" and suggested precautions in relation to operations on the elderly. Since then, many studies have investigated the incidence of and the risk factors for postoperative cognitive dysfunction (POCD). The incidence ranges from 8.9% to 46.1% and advanced age, preoperative mild cognitive impairment, extensive surgical procedures and other factors have been identified as important risk factors. The incidence has been reported to be as high as 41.4% at hospital discharge and 12.7% at 3 months after surgery in the elderly (60 years or older). Postoperative delirium (POD) is a more acute complication of major surgery, affecting 10-70% of surgical patients 60 years and older. Some studies have shown the association between POD and early POCD, and even POD and POCD are commonly reported as being part of the same continuum. Whether this is true or not, both represent postoperative cognitive deterioration, and age is the predominant risk factor for both.

Every day in the United States, nearly 100,000 patients undergo general anesthesia and sedation for surgical and diagnostic procedures. Approximately 35% of all surgical procedures are performed on adults older than 65 years. Considering the aging surgical population, the burden of postoperative cognitive disorders will almost certainly increase over time.

Although many factors, such as surgical stress, inflammation, and other comorbidities may contribute to POCD, there is evidence that anesthetic exposure plays a major role. Pre-clinical studies have demonstrated that exposure to anesthetic drugs is neurotoxic, and that older animals are particularly vulnerable. It is also generally understood that the elderly are more sensitive to anesthetics, meaning that lower doses of anesthetic drugs are required to induce and maintain unconsciousness. This has led to age-adjusted guidelines for anesthetic dosing, which in theory could be used to mitigate potentially harmful anesthetic exposures. However, these guidelines describe the age-dependent dose-response relationships for a population of patients; individual drug requirements can vary significantly, by a factor of ~2 above or below the levels recommended by population-based models. In the absence of a means to measure and monitor individual drug responses, anesthesiologists would tend to err on the side of administering more anesthetic than required, to minimize the probability of patient awareness across the population as a whole.

Fortunately, in recent years, significant progress has been made to understand the neural mechanisms of anesthesia-induced unconsciousness, making it possible to monitor individual patients' drug responses using the electroencephalogram (EEG). Increasing concentrations of the commonly-used GABAergic anesthetic drugs, such as propofol and sevoflurane, induce a stereotyped sequence of brain oscillations with increasing drug concentration. These brain oscillations are directly related to the states of sedation and unconsciousness induced by anesthetic drugs, and readily observed using the EEG. At lower concentrations, propofol and sevoflurane, two of the most commonly used anesthetic drugs, induce beta oscillations (12-25 Hz). At concentrations producing unconsciousness for general anesthesia, these drugs produce frontal alpha (8-12 Hz) and slow (0.1 to 1 Hz) oscillations. At still higher concentrations, propofol and sevoflurane produce a pattern referred to as burst suppression, a deep state of brain inactivation in which brain activity is punctuated by long periods of neuronal and EEG silence. However, it is now known that elderly patients do not always exhibit this canonical EEG signature under general anesthesia. First, it was described that ageing was associated with a decrease in the frontal alpha power. Then, other studies suggested that older patients with poor preoperative cognitive performance also lack the alpha band under anesthesia. And finally, our group demonstrated that a low alpha power is also associated with a higher risk to develop burst suppression under anesthesia. Nonetheless, the potential mechanism related to the lower alpha power with ageing and cognitive function remains unknown. In this study, we propose to evaluate the relationship between the alpha oscillation dynamics and the signals derived from brain images related to brain aging.

We hypothesize that: 1) Brain imaging signals will correlate with the alpha power induced by anesthetics, and 2) Aging brain imaging features will be associated with postoperative cognitive recovery.