R01AG070861

Digital Biomarkers for Alzheimer's Disease

Alzheimer's Disease (AD) is marked by progressive neuropathological changes that begin decades before cognitive and functional symptoms. Efforts have been focused on developing innovative tools and biomarkers for early identification of pre-dementia stages. However, the clinical ability to identify those with pre-dementia stages of AD has been limited and requires expensive (amyloid PET) or invasive (lumbar puncture) testing.

Subtle changes in connected speech may be detectable years before overt disease symptoms present. Our team has developed an approach that uses machine learning and natural language processing combined with advanced acoustic phonetic and lexical-semantic analyses. Preliminary data show promise in identifying AD biomarker status and predicting 2-year cognitive progression.

In the proposed study, we leverage our success in collecting cerebrospinal fluid (CSF) biomarkers, neuroimaging, and detailed cognitive phenotyping combined with audio recordings of participants in the Brain Stress, Hypertension, and Aging Research Program cohort. This cohort, now in its third year of follow-up, consists of 400 individuals 50 years or older with normal cognition or mild cognitive impairment. We plan to extend this cohort of 400 participants for 3 more years to collect additional waves of voice recordings, cognitive assessments, follow-up CSF biomarkers, and neuroimaging.

Our overarching hypothesis is that the derived novel features reflecting poor lexical-semantic connectedness or acoustic perturbations are significantly different between biomarker-positive and -negative participants. These features have better diagnostic performance with regards to the ATN framework than traditional cognitive tests and can track disease progression.

The specific aims of this study are:

1) Determine the accuracy of the derived digital biomarkers in detecting in-vivo AD pathology and ATN classification in the B-Sharp cohort.
2) Investigate the association of the derived digital biomarkers with disease progression and cognitive decline.
3) Investigate the ability of repeated measurement of the digital biomarkers to track disease progression.

This project will provide needed insight into the use of non-invasive digital biomarkers to improve the ability to detect and track longitudinal changes in cognitive and functional status in AD. It will also set the foundation for a future larger pivotal study.

The University Of Texas Southwestern Medical Center

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]

Texas United States

State-Wide

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

Amendment Since initial award the End Date has been extended from 05/31/26 to 05/31/27 and the total obligations have increased 2022% from $158,926 to $3,371,926.