R01AG083777

Minimizing ICU neurological dysfunction with dexmedetomidine-induced sleep (MINDDS II) - project summary / abstract

Up to a third of elderly patients recovering from cardiac surgery experience postoperative delirium (POD), an acute state of confusion marked by inattention and global cognitive dysfunction. POD is a burdensome clinical and patient-centered outcome associated with long-term cognitive deficits like Alzheimer's disease (AD) and related dementias (AD/RD), prolonged hospitalization and institutionalization, higher readmission rates, and increased mortality.

We recently found elevated tau in the serum of patients that developed POD after cardiac surgery and an association between tau and POD severity, suggesting that perioperative stressors exacerbate latent ADRD pathology, and evidence to suggest that dexmedetomidine modifies the association with preoperative tau.

Recent studies have suggested that approximately 30% to 40% of POD may be preventable. However, multicomponent nonpharmacological POD prevention strategies are resource intensive and increasingly challenging to implement given the current labor shortage in healthcare. A recent enhanced recovery and perioperative quality initiative joint consensus statement on POD prevention highlighted the need for a safe and easy-to-implement prophylactic pharmacological strategy.

At present, definitive guidelines or large clinical trials do not support the administration of any medication for POD prevention. In the pilot MINIMIZING ICU NEUROLOGICAL DYSFUNCTION WITH DEXMEDETOMIDINE-INDUCED SLEEP (MINDDS) randomized controlled trial, we found that nighttime intravenous dexmedetomidine significantly reduced the incidence of POD in patients older than 60. However, replication in a large, more pragmatic trial is warranted to support the widespread implementation of nighttime dexmedetomidine for POD prevention.

This proposal will study nighttime intravenous and sublingual dexmedetomidine to provide definitive evidence for POD prevention efficacy. Additionally, it will create a biorepository to aid biomarker discovery and insights into POD and cognitive recovery after cardiac surgery.

In Aim 1, we will perform a large (N = 1800), pragmatic, phase III, randomized, blinded, double placebo-controlled, three-arm study of nighttime dexmedetomidine for POD prevention and cognitive improvement in elderly patients following cardiac surgery. In Aim 2, we will examine the effect of nighttime dexmedetomidine on patient-reported outcomes, morbidity, and mortality. In Aim 3, we will establish a biorepository of plasma, ribonucleic, and deoxyribonucleic samples. The proposal has

The General Hospital Corporation

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]

Boston, Massachusetts 021142621 United States

Single Zip Code

Research on Current Topics in Alzheimer's Disease and Its Related Dementias (R01 Clinical Trial Optional) (PAR-22-093)

Amendment Since initial award the total obligations have increased 108% from $3,506,058 to $7,286,036.