R35AG072362

Reimagining Precision Medicine Approaches to AD Diagnosis - Project Summary

Despite advances in biomarkers, the accuracy of the diagnosis of Alzheimer's disease and related dementias (ADRD) in everyday clinical practice remains inadequate, particularly for health disparities populations. This research program addresses this challenge by validating promising, widely accessible, and inexpensive clinical and plasma-based biomarkers in diverse populations in an academic setting and in real-world clinical practice.

Our overarching goal is to reimagine approaches to the diagnosis of ADRD using scalable precision medicine tools. The proposal synergizes the research programs of co-PIs Dr. Gil Rabinovici, a behavioral neurologist and leader in brain imaging and biomarkers, and Dr. Kate Possin, a neuropsychologist and leader in innovation of tablet-based cognitive assessments and dementia care models.

We will recruit 400 participants from the UCSF Alzheimer's Disease Research Center (ADRC), which includes large, heterogeneous, deeply phenotyped clinical cohorts ranging from cognitively unimpaired to dementia, with a large Latino/Hispanic component. Additionally, we will recruit 750 participants from the New IDEAS study, which is evaluating the clinical utility of amyloid PET in Medicare beneficiaries with mild cognitive impairment (MCI) or dementia, emphasizing the recruitment of Black/African American and Latino/Hispanic patients. Collaborator Dr. Peggye Dilworth-Anderson will help develop novel enrollment approaches that attend to cultural nuances, provider workflows, and meaningful incentives to ensure inclusive research.

All participants will undergo a brief battery of domain-specific cognitive tests and surveys of social determinants of health (SDH), cognitive and functional symptoms, and caregiver factors. Blood-based biomarkers of amyloid, tau, and neurodegeneration will be measured in 1,000 participants with co-investigator Dr. Sid O'Bryant. Through this, we aim to identify vulnerability factors and care needs that will inform future diagnostic care models.

In addition to cognitive testing and surveys, all participants will undergo amyloid PET imaging. UCSF ADRC participants will also undergo tau PET and MRI. By analyzing the clinical measures and blood-based biomarkers that best predict molecular pathology, we will develop classifiers that consider patient factors, SDH, cognition, caregiver factors, and blood-based biomarkers to predict amyloid and tau PET findings, the necessity for PET imaging, and health outcomes.

Throughout the project, we will mentor and support junior and early-stage investigators, contributing to their development in the field. This project will address ADRD research implementation milestone 9.L, "Improving differential diagnosis of symptomatic cognitive impairment," while also advancing additional key milestones related to racial/ethnic diversity and blood-based biomarkers. Ultimately, this work will ready the field for the inclusive identification of appropriate candidates for disease-modifying therapies.

San Francisco Regents Of The 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]

San Francisco, California 94143 United States

Single Zip Code

Leadership Award for Alzheimer's Disease and Related Dementias Research (R35 Clinical Trial Not Allowed) (RFA-AG-21-007)

Amendment Since initial award the total obligations have increased 392% from $979,381 to $4,816,964.