RF1AG093527

OPTIMIZING SEMANTIC MEMORY MEASURES OF ALZHEIMER'S DISEASE BIOMARKERS - RECENT EVIDENCE SUGGESTS THAT NEUROPSYCHOLOGICAL TESTING IS SENSITIVE TO THE ACCUMULATION OF KEY ALZHEIMER’S DISEASE (AD) PATHOLOGIES IN OLDER ADULTS WITHOUT DEMENTIA. SEMANTIC MEMORY, MEANING FACTUAL KNOWLEDGE ABOUT THE WORLD, HAS EMERGED AS A POTENTIALLY SENSITIVE COGNITIVE DOMAIN TO EARLY AD PATHOLOGY. YET, BARRIERS LIMIT OUR UNDERSTANDING OF SEMANTIC MEMORY’S PROMISE FOR DETECTING AD-RELATED COGNITIVE DECLINE. NOTABLY, EFFORTS TO EXAMINE SEMANTIC MEMORY’S SENSITIVITY TO AMYLOID AND TAU HAVE NOT CAPITALIZED ON KEY COGNITIVE MECHANISMS - IDENTIFIED THROUGH ADVANCEMENTS IN COGNITIVE NEUROSCIENCE - THAT MAY MAXIMIZE SENSITIVITY TO AD PATHOLOGY. ADDITIONALLY, THERE REMAINS UNCERTAINTY AS TO HOW SEMANTIC MEMORY MAPS TO HIPPOCAMPAL/MEDIAL TEMPORAL LOBE (MTL) INTEGRITY, DESPITE BEING RELEVANT TO REVEALING MECHANISMS AND PROFILING AD PATHOLOGY. GUIDED BY CONTEMPORARY COGNITIVE NEUROSCIENCE THEORIES, THE PRESENT PROPOSAL AIMS TO ASCERTAIN, AMONG OLDER ADULTS WITHOUT DEMENTIA, THE SENSITIVITY OF SEVERAL NEW SEMANTIC MEMORY TASKS TO: 1) A PROMISING PLASMA BIOMARKER OF AD-SPECIFIC AMYLOID/TAU PATHOLOGY AND 2) HIPPOCAMPAL/MEDIAL TEMPORAL LOBE ATROPHY. LED BY PI DR. GRILLI, OUR TEAM COMBINES EXPERTISE IN THE COGNITIVE NEUROSCIENCE OF SEMANTIC MEMORY, HIPPOCAMPAL/MEDIAL TEMPORAL LOBE FUNCTIONING, AND THE NEUROPSYCHOLOGICAL DETECTION OF EARLY AD. TOGETHER, WE WILL UNDERTAKE AN INNOVATIVE PROJECT INTEGRATING NOVEL COGNITIVE ASSESSMENT, COMPREHENSIVE NEUROPSYCHOLOGICAL PROFILING, STRUCTURAL MRI, AND PLASMA ASSAYS. WE WILL TEST, AMONG 225 OLDER ADULTS SPANNING FROM COGNITIVELY UNIMPAIRED TO THOSE WITH MILD COGNITIVE IMPAIRMENT, THE RELATIONSHIPS BETWEEN AD BIOMARKERS AND SEVERAL MECHANISMS OF SEMANTIC MEMORY FUNCTIONING. IN AIM 1, WE WILL INVESTIGATE WHETHER ADDING PRECISION TO SEMANTIC MEMORY ENHANCES THIS COGNITIVE CONSTRUCT’S SENSITIVITY TO AD BIOMARKERS, AS MEASURED BY PLASMA AND HIPPOCAMPAL/MEDIAL TEMPORAL LOBE ATROPHY. AIM 2 WILL EXPLORE OUR HYPOTHESIS THAT EXPERIENCE-NEARNESS, ANOTHER PROPERTY OF SEMANTIC MEMORY, IS SENSITIVE TO THE SAME AD BIOMARKERS. FINALLY, AIM 3 WILL ASSESS OUR HYPOTHESIS THAT GENERATIVE PROCESSING, AS A THIRD SEMANTIC MEMORY PROPERTY, CAN DETECT EARLY SIGNS OF AD THROUGH OUR TARGET BIOMARKERS. ALL THREE AIMS ARE NOT ONLY INFORMED BY CONTEMPORARY THEORY BUT ALSO SUPPORTED BY EXTENSIVE PRELIMINARY DATA FROM OUR TEAM. THE AIMS ALSO ARE ALIGNED WITH THE NIH’S NOTICE OF SPECIAL INTEREST: NOVEL APPROACHES TO DIAGNOSING AND STUDYING CLINICAL ALZHEIMER'S DISEASE AND RELATED DEMENTIAS (NOT-AG-21-036). THIS PROJECT, TO OUR KNOWLEDGE, WILL BE THE FIRST TO EVALUATE THE SENSITIVITY OF THESE THREE SEMANTIC MEMORY PROPERTIES TO CRITICAL, EARLY AD BIOMARKERS. ULTIMATELY, THE RESULTS OF THIS PROJECT MAY LEAD TO THE DEVELOPMENT OF MORE SENSITIVE AND SPECIFIC COGNITIVE TOOLS FOR EARLY TRACKING OF AD-RELATED PATHOLOGIES, WITH BROAD IMPLICATIONS FOR SCIENTISTS CONDUCTING CLINICAL TRIALS, AS WELL AS CLINICIANS ON THE FRONTLINE OF HEALTHCARE TREATMENT. THE KNOWLEDGE GAINED ALSO MAY SIGNIFICANTLY ADVANCE OUR UNDERSTANDING OF HIPPOCAMPAL/MEDIAL TEMPORAL LOBE FUNCTIONING BY CLARIFYING THE MECHANISTIC ROLE OF THESE NEURAL STRUCTURES IN SEMANTIC MEMORY.

University Of Arizona

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]

Tucson, Arizona 85721 United States

Single Zip Code

Research on Current Topics in Alzheimer's Disease and Its Related Dementias (R01 Clinical Trial Optional) (PAR-22-093)