R01AG085571

Cerebral tau deposition and comorbid cerebrovascular disease across the Alzheimer's disease continuum in Mexican Americans - Summary: Alzheimer's disease (AD) and related dementias (ADRD) disease burden is anticipated to affect diverse ethnic and racial groups disproportionately, with the most staggering increase of nearly 6-fold impacting Hispanics.

Nonetheless, there is a lack of scientific research on Hispanic adults, particularly among the most populous Mexican American (MA) demographic, fostering a poor understanding of the mechanisms contributing to the observed disparities.

Tau deposition is strongly linked to cognitive decline in AD and can be visualized in vivo with sensitive and specific positron emission tomography (PET) tracers such as 18F-MK-6240.

Data from our team and others indicates that artificial intelligence (AI) methods that quantify tau deposition patterns specific to AD may optimize detection of early disease risk and better predict cognitive decline.

Unfortunately, few studies have been conducted in diverse cohorts, which limits generalizability and may precipitate further inequities in AD diagnosis and treatment.

In addition, gaps remain in our understanding of the impact of mixed dementia pathologies on cognition.

AD and cerebrovascular disease (CVD) commonly co-occur and may have a larger impact on disease presentation in MA adults relative to non-Hispanic white (NHW) adults due to socio-economic disparities and broader social determinants of health (SDOH) that increase cardiovascular risk factors (CVRFS).

We now propose to develop and validate traditional and novel tau PET imaging and CVD measures in a longitudinal cohort of 500 MA older adults (N=150 cognitively unimpaired (CU), N=150 mild cognitive impairment (MCI), N=200 AD dementia) from the South Texas Alzheimer's Disease Research Center and the Nantz National Alzheimer's Center.

We will assess the diagnostic accuracy of traditional and AI-derived tau PET indices and examine their associations with longitudinal cognitive decline (Aim 1).

We also evaluate associations between the tau PET measures and ADRD plasma biomarkers in order to facilitate efforts to utilize blood-based biomarkers for initial diagnostic screening and clinical trial stratification.

Next, we will evaluate the interactive effects of tau and CVD burden on cognition and will employ causal interference modeling to elucidate the pathways linking SDOH and modifiable CVRFS with ADRD (Aim 2).

Leveraging the resource of harmonized clinical and neuroimaging data on 200 NHW adults from the Nantz National Alzheimer's Center, we will examine the hypothesis that ethnic disparities in ADRD will be mediated through these pathways.

Finally, we will validate our imaging and plasma biomarker findings in an independent sample of 1,000 Hispanic and 1,000 NHW older adults participating in the community-based HABS-HD study (Aim 3).

Our proposal will provide important insights into the diagnostic accuracy of traditional and novel tau PET measures.

We will further examine the overlay of tau pathology with broader ADRD neuroimaging and blood biomarkers in an effort to advance the understanding of ADRD heterogeneity and optimize early disease detection.

Finally, we systematically evaluate the underlying pathways linking SDOH and modifiable CVRFS with ADRD, which may be leveraged to attenuate health disparities.

The University Of Texas Health Science Center At San Antonio

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]

San Antonio, Texas 782293901 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 96% from $2,919,399 to $5,730,361.