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2008 Grants - Monk
Does Inhalational Anesthesia Accelerate Postoperative Cognitive Decline?
Terri Monk, M.D.
Duke University Medical Center
Durham, North Carolina
2008 Investigator-Initiated Research Grant
Older adults often experience cognitive problems, including dementia, after undergoing major surgery. Several recent studies have found that the progression of Alzheimer's disease is accelerated by inhaled forms of anesthesia taken before surgery. The main agent in these anesthesias, a compound called isoflurane, appears to promote the accumulation of beta-amyloid in animal brains. Beta-amyloid is a protein fragment likely involved in Alzheimer's. Thus isoflurane may be the agent responsible for accelerated Alzheimer progression.
Though inhaled anesthesia remains commonly used for surgical procedures, many surgeons are beginning to replace the inhaled form with an injected anesthesia called total intravenous anesthesia (TIVA). The primary compound in TIVA is propofol. In studies with cultured cells and animals, researchers have found that propofol does not promote beta-amyloid production or accumulation. Thus TIVA may prove a far safer anesthetic alternative for people with dementia or at risk of dementia.
Terri Monk, M.D., and colleagues plan to investigate the safety of TIVA in a clinical study with 200 elderly participants undergoing major orthopedic surgery. The participants will randomly receive either isoflurane-based inhaled anesthesia or propofol-based TIVA for their procedures. Participants will also receive thorough cognitive and functional evaluations prior to surgery and at three months and one year after surgery. The researchers will compare how each treatment affected the individuals' cognitive and functional abilities over time.
In addition, Dr. Monk's team will identify which of the participants possessed the E4 variant of a gene known as ApoE. This gene variant is associated with a greater risk for developing Alzheimer's, and the investigators want to determine how its presence might affect the cognitive decline associated with inhaled anesthesia.
The long-term objective of this study is to reduce aging-related cognitive deterioration after major surgery, a problem likely to become more common as elderly populations in many countries increase.