R01AG078191

Depression and Alzheimer's Disease: Catastrophy?

Abstract

Better understanding the interface of depression and Alzheimer's disease (AD) pathology could lead to new strategies to prevent or slow cognitive decline, with significant public health impact. Depression has historically been neglected and/or excluded in observational cohort and clinical trial research on AD, so we have limited knowledge about its relationship with pathological hallmarks of AD and cognitive decline.

Our data suggest an association between tau and depression that may potentiate cognitive decline in preclinical stages of AD—when amyloid are below PET positivity thresholds—and confer dementia risk. Currently, the model of tau-associated depressive symptoms needs to be validated across the full spectrum of depressive symptom severity, including major depressive disorder (MDD). The current study was designed to address this critical gap.

Our overarching goal is to investigate the relationships between tau and depressive symptoms over time in cognitively unimpaired older adults using both longitudinal tau PET (with spatiotemporal resolution) and novel plasma tau measures (with greater potential for clinical translation than PET or CSF) that are gaining rapid readiness for clinical translation). Achieving this goal will help characterize the risk of cognitive decline for older adults with clinically significant depressive symptoms, optimize approaches to depression evaluation, and provide potential opportunities for early recognition and prevention of AD.

Our primary hypothesis is that tau in temporal brain regions will predict more severe depressive symptoms, and that greater depressive symptoms will potentiate tau-associated cognitive decline. We will test these hypotheses in 150 cognitively unimpaired older adults across the spectrum of depression (subclinical to major depressive disorder [MDD]) integrating longitudinal affective and cognitive symptom characterization, tau PET, and tau plasma biomarker assessments.

This is the first study to our knowledge to investigate longitudinal tau PET and plasma measures in a cohort of older adults across the full range of depressive symptom severity. Better understanding of the mechanisms underlying depressive symptoms in preclinical AD could inform prevention efforts, including tau measurement as a means of identifying risk in older adults with late-life depression. Thus, we will address the FOA goal "to encourage biomedical, behavioral, and social sciences research that will enhance knowledge of mechanisms underlying neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) or Alzheimer's disease-related dementias (ADRD) so as to enable novel treatment development."

The General Hospital Corporation

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]

Charlestown, Massachusetts 02129 United States

Single Zip Code

Novel Mechanism Research on Neuropsychiatric Symptoms (NPS) in Alzheimer's Dementia (R01 Clinical Trial Optional) (PAR-20-157)

Amendment Since initial award the total obligations have increased 292% from $821,468 to $3,218,523.