10 Clinical Trials for Various Conditions
The purpose of this project is to investigate the role of both neural inflammation and pre-existing neurodegenerative pathology in the risk and pathogenesis of post-operative cognitive dysfunction (POCD). To achieve this goal, the investigators will combine blood and cerebrospinal fluid (CSF) sampling, standardized cognitive tests, and dynamic neurophysiological markers of cortical network dysfunction in the form of event-related potentials (ERPs), to assess the link between neurodegeneration and neuroinflammation in the pathogenesis of POCD.
(From NIH reporter) Each year \>16 million older Americans undergo anesthesia and surgery, and up to 40% of these patients develop postoperative cognitive dysfunction (POCD), a syndrome of postoperative thinking and memory deficits. Although distinct from delirium, POCD (like delirium) is associated with decreased quality of life, long term cognitive decline, early retirement, increased mortality, and a possible increased risk for developing dementia such as Alzheimer's disease. Understanding the etiology of POCD will likely help promote strategies to treat and/or prevent it. A dominant theory holds that brain inflammation causes POCD, but little work has directly tested this theory in humans. The preliminary data of this team strongly suggest that there is significant postoperative neuro-inflammation in older adults who develop POCD. In this K76 award, the investigators will prospectively obtain pre- and post-operative cognitive testing, fMRI imaging and CSF samples in 200 surgical patients over age 65. This will allow the investigators to evaluate the role of specific neuro-inflammatory processes in POCD and its underlying brain connectivity changes.
The use of desflurane in elderly subjects (\>65 years old) undergoing general anesthesia with endotracheal intubation will result in decreased POCD compared to sevoflurane if the patient's MAP is within 20% of the patient's baseline and the cerebral suppression state index stays within the moderately anesthetized range during general anesthesia.
This study will recruit surgical patients more than 65 years old. Patients who participate will wear a sticker on their forehead during surgery which monitors their brain waves (electroencephalogram, EEG) and participate in memory testing before and after surgery. Brain wave patterns will be compared between patients who have problems with memory and thinking after surgery and those who do not. The hypothesis is that there will be characteristic brain wave patients for who will go on to have problems with memory and thinking after surgery.
Elderly patients who undergo anesthesia and non-cardiac surgery are subject to deterioration of brain function including the development of postoperative delirium (PD) and postoperative cognitive dysfunction (POCD). These disorders cause disability, distress for both patients and their families, are associated with other medical complications and account for significant additional health care costs. We currently use relatively primitive approaches to preventing and treating PD and POCD. Dexmedetomidine is a drug used for sedation in critically ill patients that provides some pain relief and controls the bodies response to stress. The sedation produced by dexmedetomidine appears more similar to natural sleep than any other drug used for anesthesia and postoperative sedation. Data suggesting that dexmedetomidine can prevent delirium following cardiac surgery and the developing understanding of the causes of PD and POCD suggest that dexmedetomidine will be particularly effective.
This is a pilot study to evaluate the effect of dexmedetomidine in the prevention of delirium in non-cardiac surgical patients. The preliminary data regarding the effect of dexmedetomidine on delirium comes from a study underway at Stanford. We propose to randomize fifty patients into two different protocols, one using dexmedetomidine until PACU discharge (hip replacement) and the other using dexmedetomidine for 24 hours in a monitored setting.
Postoperative cognitive decline (POCD) affects up to 50% of non-cardiac surgical patients greater than or equal to 65 years of age. This study will test the hypothesis that preoperative presence of brain beta-amyloid plaques in non-demented subjects increases postoperative cognitive decline (POCD) in elderly subjects scheduled for hip or knee replacement. The investigators hypothesize that preoperative beta-amyloid plaques will predict postoperative cognitive decline.
Recent data suggests that anesthetics can have prolonged effects on gene expression, protein synthesis and processing as well as cellular function in ways that the investigators are only beginning to understand, especially in the very young and the elderly. Within moments to days of emerging from anesthesia - cardiac or non-cardiac - some patients experience mild to very severe disorientation and changes in memory and thinking ability without apparent cause. For the vast majority of patients, this Post-Operative Cognitive Dysfunction (POCD), generally subsides, but for some with "diminished cognitive reserve" - especially the elderly, those with less education or prior CNS events such as stroke or early dementia - changes in memory and executive function may persist. If prolonged for more than three months, POCD has been linked to an increased risk of death. In 1-2% of elderly patients, the problem may ultimately continue for more than a year, leading to a loss of ability to care for themselves and early demise. Though this may seem like a small percentage, seniors will comprise up to 40% of the 50-75 million surgical procedures performed annually over the next 20-30 years. This amounts to 70,000 - 200,000 elder affected, and for them and their families, the cost of POCD in longer-term care, lost wages, and extended suffering will remain very high.
The purpose of this study is to determine whether brain oxygenation measured by cerebral oximeter has an impact on neurocognitive dysfunction.
While hypotension during general anesthesia has routinely been considered to be a tolerable abnormality with little clinical consequence, the proposed study takes the innovative approach of defining hypotensive events within the construct of a patient's own hypertensive status, fractional mean arterial blood pressure (fMAP). Because the investigators primary variable is within the control of anesthesia personnel, the study portends a potentially simple and easy to implement treatment. The introduction of neuropsychometric measures as the relevant evaluator of post-operative cognitive dysfunction is innovative, and may be more relevant to the average elderly patient than simple mortality.