R01AG074185

Neurocognition and Greater Maintenance of Sinus Rhythm in AF (NOGGIN AF) - Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting 1%-3% of the general population, with greater prevalence in older persons (8%-10%). AF is associated with an increased risk for cognitive decline, dementia, stroke, myocardial infarction, heart failure, chronic kidney disease, and mortality, resulting in an incremental yearly cost of AF in the US of $26 billion.

AF and cognitive decline share several risk factors including advancing age and comorbidities such as hypertension, diabetes mellitus, and heart failure. Microbleeds from anticoagulation, a proinflammatory and prothrombotic state, and cerebral hypoperfusion can cumulatively result in silent cerebral infarction, white matter hyperintensities, brain atrophy, and disruption of functional network connectivity, and also lead to AF-related cognitive decline.

While the link between AF and the development of cognitive impairment has been established, the driving mechanisms and the effect of sinus rhythm restoration are not completely understood. Our long-term goals are to understand the interaction between heart rhythm and neurologic health, and to investigate methods to prevent cognitive dysfunction due to AF.

Thus, in the proposed study, we will test our hypothesis that among AF patients receiving oral anticoagulation, restoration of sinus rhythm with catheter ablation vs drug therapy leads to less long-term neurologic damage and dysfunction due to improved cerebral blood flow and lower risk for additional ischemic injury.

The primary aims of our prospective, observational clinical trial are to:

1) Compare structural cortical characteristics in Alzheimer's disease-risk regions in AF patients treated with catheter ablation vs drug therapy;
2) Compare cerebral blood flow in AF patients treated with catheter ablation vs drug therapy;
3) Compare cognitive function in AF patients treated with catheter ablation vs drug therapy;
4) Assess the relationship between neurologic outcomes and plasma and imaging biomarkers of coagulation and inflammation.

This will be the first study to incorporate a comprehensive neurocognitive test battery, structural and functional neuroimaging, cerebral blood flow assessment, and plasma and imaging biomarkers to:

A) Better delineate the contribution of each of the known risk factors to the development of cognitive decline in patients with AF, and
B) Assess how restoration of sinus rhythm using catheter ablation vs drug therapy may alter the trajectory of cognitive decline and development of dementia.

Our preliminary data showed that catheter ablation did not worsen cognitive function or white matter hyperintensity burden 6 weeks or 1 year later, while drug therapy patients showed greater cortical thinning at 1 year in brain regions associated with Alzheimer's, and this thinning correlated with worse cognitive performance.

Thus, this study is significant and will vertically advance the field of AF management by revolutionizing our understanding of the mechanisms by which AF induces cognitive decline, and by providing an important and necessary step toward justifying rhythm control by catheter ablation as a strategy to arrest the processes that lead to cognitive impairment and dementia.

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 277054699 United States

Single Zip Code

Research Project Grant (Parent R01 Clinical Trial Required) (PA-20-183)

Amendment Since initial award the total obligations have increased 403% from $740,086 to $3,724,610.