R01AG073244

Emotion Alterations Across the Alzheimer's Disease Spectrum - Abstract

Changes in emotion and social behavior are early yet overlooked features of Alzheimer's Disease (AD). In AD, there is progressive accumulation of beta amyloid (ASS) and tau proteins, a pathological process that leads to neurodegeneration and functional connectivity alterations in distributed brain networks.

Episodic memory decline is a hallmark feature of typical amnestic AD presentations, but AD can also cause atypical dysexecutive/amnestic, language (i.e., logopenic variant primary progressive aphasia [LVPPA]), and visuospatial (i.e., posterior cortical atrophy [PCA]) syndromes.

In typical AD, default mode network dysfunction is accompanied by elevated functional connectivity in the salience network, a system that supports emotion generation and interoception. Enhanced salience network connectivity in AD is associated with greater affective symptoms such as anxiety.

Our previous studies have found that specific types of emotional empathy, a rudimentary form of affect-sharing, are elevated in typical AD and relate to default mode network atrophy. Whether emotion elevations are present in atypical AD syndromes is unknown but are suggested by clinical and neuroimaging data.

There is emerging evidence that gains in emotional empathy are evident even in preclinical AD, a prodromal phase in which people have signs of AD pathology on biomarker testing but lack cognitive symptoms.

A central hypothesis of this proposal is that early neuropathology and neurodegeneration in AD-vulnerable networks disinhibits the salience network and elevates emotion functioning across AD syndromes.

A more detailed understanding of emotion in AD will help to improve diagnosis by broadening current conceptualizations of each syndrome, to identify emotion measures that suggest the presence of early AD, and to uncover new biomarkers that change as neuropathology affects emotion-relevant brain networks.

In the proposed studies, we will conduct laboratory-based assessments of emotion (i.e., autonomic nervous system activity, facial behavior, and subjective experience) in 200 people with AD, as indicated by elevated ASS (ASS+) and tau deposition on molecular PET scans (110 amnestic/dysexecutive AD, 45 LVPPA, and 45 PCA), and 150 older healthy controls with and without AD pathology (75 ASS+ and 75 ASS-) with varying levels of tau pathology.

By relating emotion measures to clinical data, structural and functional connectivity, ASS and tau burden, and affective symptoms, we will address three key aims.

In Aim 1, we will quantify emotion, empathy, and social behavior in AD syndromes and ASS+ healthy controls.

In Aim 2, we will delineate the structural and functional neural networks underlying emotion alterations across the AD spectrum.

In Aim 3, we will elucidate associations among ASS and tau pathology, emotion system functioning, and affective symptoms.

By forging links among measures of emotion, neural network dysfunction, affective symptoms, and ASS and tau deposition, the proposed research will help to broaden models of AD's earliest manifestations and to elucidate how specific neuropathological changes alter emotion systems and relate to affective symptoms.

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

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

Amendment Since initial award the total obligations have increased 386% from $820,088 to $3,988,892.