R01AG073598

Low Neurophysiologic Resistance to Anesthetics as a Marker of Preclinical/Prodromal Alzheimer's Disease and Neurovascular Pathology, Delirium Risk and Inattention - Project Summary/Abstract

Delirium is a syndrome of fluctuating changes in alertness and attention that occurs in up to 40% of older surgical patients (i.e. age >65). Delirium is associated with an increased risk of developing dementia, a progressive loss of thinking and memory skills that eventually results in an inability to care for oneself and to live independently.

The most common cause of dementia in older Americans is Alzheimer's disease (AD), which is associated with a progressive buildup of abnormal deposits in the brain of two proteins, tau and amyloid beta. Amyloid beta deposits typically develop in the brain for years if not decades before the start of memory deficits and other AD symptoms. Patients with these early or "pre-clinical" amyloid beta deposits, even if they appear mentally normal, are often at increased risk of developing delirium after surgery.

Here, we will examine whether these amyloid beta deposits, or other "pre-clinical" changes in brain structure and activity, predispose patients to show larger than normal brain activity changes in response to anesthetic drugs given during surgery. The central idea of this proposal is that an altered (or exaggerated) brain activity response to anesthetic drugs is a marker of an unhealthy brain, i.e. a brain with signs of "pre-clinical" AD and which is at increased risk of postoperative delirium.

First, we will examine whether patients with evidence of brain amyloid beta pathology (as measured by spinal fluid amyloid beta levels) have altered brain activity responses to anesthetic drugs. Second, we will use brain imaging to determine whether changes early AD-like changes in brain structure and connections are associated with altered brain activity responses to anesthetic drugs. Third, we will determine whether altered brain activity responses to anesthetic drugs are associated with increased postoperative delirium occurrence and severity.

This work will help us understand mechanisms underlying postoperative delirium and AD and related dementias, and the links between them. Furthermore, this work will provide a way for anesthesiologists (and surgeons) to use brain activity recording data already in wide use in American operating rooms to predict which patients are likely to develop postoperative delirium and/or AD, which could allow these patients to be selected for interventions to prevent these disorders.

Duke University

TO ENCOURAGE BIOMEDICAL, SOCIAL, AND BEHAVIORAL RESEARCH AND RESEARCH TRAINING DIRECTED TOWARD GREATER UNDERSTANDING OF THE AGING PROCESS AND THE DISEASES, SPECIAL PROBLEMS, AND NEEDS OF PEOPLE AS THEY AGE. THE NATIONAL INSTITUTE ON AGING HAS ESTABLISHED PROGRAMS TO PURSUE THESE GOALS. THE DIVISION OF AGING BIOLOGY EMPHASIZES UNDERSTANDING THE BASIC BIOLOGICAL PROCESSES OF AGING. THE DIVISION OF GERIATRICS AND CLINICAL GERONTOLOGY SUPPORTS RESEARCH TO IMPROVE THE ABILITIES OF HEALTH CARE PRACTITIONERS TO RESPOND TO THE DISEASES AND OTHER CLINICAL PROBLEMS OF OLDER PEOPLE. THE DIVISION OF BEHAVIORAL AND SOCIAL RESEARCH SUPPORTS RESEARCH THAT WILL LEAD TO GREATER UNDERSTANDING OF THE SOCIAL, CULTURAL, ECONOMIC AND PSYCHOLOGICAL FACTORS THAT AFFECT BOTH THE PROCESS OF GROWING OLD AND THE PLACE OF OLDER PEOPLE IN SOCIETY. THE DIVISION OF NEUROSCIENCE FOSTERS RESEARCH CONCERNED WITH THE AGE-RELATED CHANGES IN THE NERVOUS SYSTEM AS WELL AS THE RELATED SENSORY, PERCEPTUAL, AND COGNITIVE PROCESSES ASSOCIATED WITH AGING AND HAS A SPECIAL EMPHASIS ON ALZHEIMER'S DISEASE. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.866 - Aging Research

National Institute on Aging (NIA) [HHS - NIH]

Durham, North Carolina 27705 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 322% from $784,183 to $3,308,332.