R01AG072681

Building an Unbiased Pooled Cohort for the Study of Lifecourse Social and Vascular Determinants of Alzheimer's Disease and Related Disorders - Abstract

Critical social and vascular risk factors for Alzheimer's Disease and Related Dementias (ADRD) occur in childhood, early adulthood, or midlife, decades before ADRD is typically diagnosed. Most cohorts dedicated to the study of aging are initiated in mid to late life and are therefore not ideal for evaluating the effects of early life risk factors.

Synthetic cohorts, which pool multiple data sources that in combination span early to late life, provide an unparalleled opportunity to rigorously evaluate lifecourse mechanisms of ADRD. Lifecourse research, especially when based on synthetic cohorts, faces several methodological challenges related to survival, enrollment, and attrition that are differential across the pooled studies, and reverse causation from incipient dementia.

The long-term goal of our research is to pinpoint how and when we can intervene to prevent or delay the onset of ADRD. Yet, the differential selection forces in a synthetic cohort can make it impossible to identify protective factors, can spuriously make harmful factors appear innocuous, and can provide incorrect guidance on prevention priorities.

In this study, we propose to pool eight data sources comprising children, young, middle-aged, and older adults to create a synthetic birth cohort for research on ADRD (SYNBAD), correcting for differential survival, enrollment or attrition, and reverse causation, allowing us to rigorously evaluate the effects of lifecourse social and vascular risk factors.

SYNBAD will include the Bogalusa Heart Study, the Muscatine Study, the National Longitudinal Survey of Youth 1979, the National Longitudinal Study of Adolescent to Adult Health, the Coronary Artery Risk in Development in Young Adults, the Health and Retirement Study, the Reasons for Geographic and Racial Disparities in Stroke, and the National Health and Nutrition Examination Studies.

SYNBAD will be large (N=304,171) and exceptionally diverse, facilitating research on the drivers of ADRD among women (56%) and Black individuals (25%). Specifically, we propose to:

(Aim 1) Create a diverse synthetic birth cohort (age 0 to 90) for the study of social and vascular risk factors for ADRD, incorporating corrections for differential survival, enrollment, and attrition;

(Aim 2) Evaluate and correct for reverse causation -- in which incipient dementia induces changes in risk factors -- by using a reverse Mendelian randomization approach based on identifying the age-specific effects of a genetic risk score for ADRD on risk factors;

(Aim 3) Rigorously estimate the causal effects of social and vascular factors on ADRD risk using the synthetic cohort corrected for selection and reverse causation biases;

(Aim 4) Quantify reduction in lifetime ADRD cases and ADRD racial disparities that could be achieved with a variety of hypothetical interventions on social or vascular risk factors at different ages.

Given the role of biological sex with social and vascular risk factors and dementia risk, we will allow for distinct risk models for men and women. This study will improve the validity of lifecourse research using synthetic cohorts and provide more valid and public health relevant estimates of the effects of social and vascular determinants of ADRD.

The Trustees Of Columbia University In The City Of New York

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]

New York, New York 100323727 United States

Single Zip Code

Research on Current Topics in Alzheimer's Disease and Its Related Dementias (R01 Clinical Trial Optional) (PAR-19-070)

Amendment Since initial award the total obligations have increased 389% from $814,437 to $3,985,562.