R01AG070088

Linking Olfactory Deficits to Memory Impairment and AD Neurodegeneration - Abstract

Olfactory impairment may signal prodromal Alzheimer's disease (AD). We currently do not have an established model that can be tested, in vivo, relating AD neurodegeneration to specific functional deficits in olfaction and memory. This significant knowledge gap impedes the development of functional imaging markers for the evaluation and diagnosis of AD.

We have developed several olfactory fMRI paradigms that can probe the dysfunctions in brain regions where early stage AD neurodegeneration occurs. Our preliminary data suggest an AD neurodegeneration-to-function model. We hypothesize that progressive neurodegeneration in MCI disrupts the connectivity of the olfactory network (ON) to the default mode network (DMN) via the hippocampus, leading to early deficits in olfaction followed by memory impairment.

Our research is designed to test this hypothesized model using functional connectivity (FC; synchrony among brain regions) in resting state fMRI and effective connectivity (EC; directed interactions between brain regions) during olfactory task fMRI; neurodegeneration will be evaluated by volumetric MRI (VMRI).

Aim 1: Determine age-related changes in the ON-DMN network in cognitively normal subjects.

Aim 2: Determine changes in the ON-DMN network in mild cognitively impaired (MCI) subjects.

Aim 3: Explore the relationships between progressive changes in the ON-DMN network and cognitive decline in MCI subjects.

The overarching goal of the proposed research will be to rigorously test an AD neurodegeneration model that answers two fundamental questions: a) How are odor-identification and odor-discrimination deficits in AD related to memory impairment and neurodegeneration? And b) Do olfactory deficits and progressive disruptions to ON-DMN connectivity signal the development of AD dementia?

Research outcomes can provide numerous avenues for improving olfactory testing as an AD marker. Olfactory tests, which target specific brain areas and processes that are affected earliest in AD, could hold additional promise for early disease detection and prevention in other neurodegenerative diseases, such as Parkinson's disease.

Pennsylvania State University

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]

Hershey, Pennsylvania 170332360 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 395% from $790,767 to $3,917,275.