R01AG095017

Discovery and trial ready cohort for limbic predominant age related TDP-43 encephalopathy (TRC LATE) - Abstract

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is a common pathological change that significantly contributes to cognitive decline in older adults and plays a critical role in Alzheimer’s-type dementia in older age groups.

LATE-NC is prevalent in over one-third of participants and half of dementia decedents in aging cohorts, often mimicking Alzheimer’s disease neuropathologic change (ADNC) with an amnestic presentation.

LATE-NC and ADNC frequently coexist, leading to multiple-etiology dementia (MED).

Despite recent progress in efforts to establish diagnostic criteria for LATE, significant gaps remain in validation of diagnostic criteria, LATE biomarkers, and recruitment strategies for early-phase clinical trials targeting LATE-NC.

This project aims to address these unmet needs by creating a discovery and trial ready cohort for LATE (TRC LATE) through recruiting and characterizing 420 participants aged 85 and older across five Alzheimer’s disease research centers (ADRCs).

These participants will undergo comprehensive annual assessments, including neuropsychological testing, annual brain MRI, FDG-PET scan every 2 years, annual blood collections, remote cognitive assessments, and recruitment science experiments.

Approximately 200 of the participants who fulfill the current LATE diagnostic criteria will be enrolled in the trial-ready cohort for enrollment in future early phase trials of LATE.

The study aims to validate clinical, neuropsychological, and imaging markers for LATE (Aim 1), identify novel biomarkers and develop risk scores for LATE-NC (Aim 2), and conduct trial planning and recruitment science studies, which will focus on identifying barriers to participation in clinical trials and evaluating methods to improve understanding and willingness to engage in LATE and LATE/AD combination trials (Aim 3).

By establishing this diverse, well-characterized cohort, we will generate crucial data to accelerate early-phase clinical trials targeting LATE-NC, discover new biomarkers, and develop new strategies for recruiting traditionally underrepresented populations in ADRD research.

Ultimately, this study will reduce trial timelines and enhance our understanding of the clinical complexities of aging-related dementias.

Irvine University Of California

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]

California United States

State-Wide

Early- and Late-Stage Clinical Trials for the Spectrum of Alzheimer's Disease/Alzheimer's Disease-Related Dementias and Age-Related Cognitive Decline (R01 Clinical Trial Optional) (RFA-AG-25-011)

Amendment Since initial award the total obligations have increased 19% from $2,636,751 to $3,128,129.