EEG-guided analgesic titration during general anesthesia to improve early neurocognitive recovery in older patients

We intend to improve brain health in elderly patients undergoing surgery by EEG-guided optimization of pharmacologic decision-making during anesthesia. Alzheimer's disease (AD), the most common form of dementia, frequently co-occurs with surgery in this population. A significant concern is post-operative delirium (POD), a state of confusion and agitation that can worsen cognitive decline. Roughly 65% of elderly surgical patients experience POD, leading to increased hospital readmissions and mortality. Notably, medications used during surgery, particularly sedatives and analgesics, can influence POD risk. Our research explores the potential of brainwave activity, specifically alpha waves measured by electroencephalogram (EEG), to predict intraoperative nociception and guide medication administration. We hypothesize that maintaining alpha waves during general anesthesia reduces the risk of POD. To test this hypothesis, we will conduct a clinical trial involving elderly surgical patients undergoing surgery under general anesthesia with frontal EEG recording. Participants will be stratified by confirmed diagnosis (AD, mild cognitive impairment (MCI), or no cognitive impairment), age, sex, surgery type, and pre-operative cognitive status. Following stratification, they will be randomized to receive either usual care anesthesia or anesthesia protocols incorporating intraoperative analysis of alpha power in the frontal EEG. This study has three main aims: (1) Investigate the influence of EEG-based protocols on alpha waves and POD prevention: We will assess if anesthesia protocols guided by real-time analysis of EEG data can enhance frontal alpha wave activity and consequently decrease the incidence of POD. (2) Evaluate the effects of dexmedetomidine on alpha waves and POD: Dexmedetomidine is a medication with both analgesic and sedative properties. We will determine if its use during anesthesia promotes alpha waves and reduces the occurrence of POD. (3) Examine the association between improved post-operative pain management and alpha power or drug administration: We will investigate whether better post-operative pain control is more closely linked to maintaining alpha waves intraoperatively or to the specific medications administered during surgery. Plasma biomarkers associated with AD will also be obtained from participants pre- and postoperatively. Furthermore, we will assess the effects of anesthesia intervention on long-term cognitive outcomes at 12 months post-surgery. This project combines real-time quantitative analysis of neurophysiological data (EEG), evidence-based pharmacological interventions (specifically targeting medication use based on alpha wave activity), and comprehensive neurocognitive assessments (performed preoperatively, postoperatively, and at a 12-month follow-up). By exploring the use of EEG-guidance for intraoperative pharmacological decisions, we aim to not only develop strategies for reducing POD risk but also gain a deeper understanding of the potential mechanistic link between POD and AD. This knowledge could ultimately lead to the development of strategies to reduce the risk of dementia in elderly surgical patients. Project Number: 1R01AG093122-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute on Aging (NIA) | Principal Investigator: Paul Garcia | Institution: COLUMBIA UNIVERSITY HEALTH SCIENCES, NEW YORK, NY | Award Amount: $577,122 | Activity Code: R01 | Study Section: Special Emphasis Panel[ZRG1 AN-W (55)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11301435