R01AG070821

Depression Treatment and AD Dynamics: A Study of Alzheimer's Disease Risk - Project Summary

Ten percent of adults over 65 suffer from Alzheimer's disease (AD), and this number is projected to double by 2050. Thus, understanding and reducing AD risk factors is of critical importance, particularly in the absence of an effective treatment.

Epidemiological evidence suggests that depression throughout the lifespan contributes to AD risk, although depression in late life also may be part of the dementia prodrome. Clinicopathological studies have provided robust support for the importance of amyloid-beta (Aβ) deposition in the pathogenesis of AD, and evidence supports an association between Aβ and depression. However, most studies that have examined the relationship between Major Depressive Disorder (MDD) and Aβ have included individuals with mild cognitive impairment (MCI), complicating our understanding of the relationship between MDD and Aβ.

Levels of soluble Aβ are influenced by the presence of deposited Aβ, and our preliminary data suggests that they also are associated with the severity of depression symptoms. Using a number of depression rating scales, our data also show that changes in residual symptoms in people with geriatric depression who do not have significant cognitive decline are correlated with Aβ changes in both cerebrospinal fluid (CSF) and plasma. However, the direction and nature of the causal relationship between MDD symptoms and Aβ peptide levels are unknown.

Given the relationship between Aβ and AD risk, elucidating the relationship between amyloid dynamics and depression symptoms would allow us to better understand the mechanism for heightened AD risk imparted by MDD. Since the direction of causation between depression and Aβ is unknown, the only way to understand cause and associated risk is to treat the depressive symptoms and examine the effects on AD biomarkers in relation to antidepressant treatment response.

We propose to study 90 cognitively-normal older adults with current episodes of MDD and no evidence of MCI in an 8-week, parallel-group, double-blind, placebo-controlled randomized study using the SSRI antidepressant escitalopram. The hypothesis is that a reduction in depressive symptoms and treatment response will be associated with an increase in the levels of CSF Aβ40 and Aβ42, as well as a reduction in vascular dysfunction markers, including platelet activation.

The results of the proposed clinical trial will build on our understanding of the relationship between MDD symptoms and the biological variables implicated in AD, and thus provide a significant target for reducing AD risk. If successful, this approach might lead to more effective strategies for reducing the risk of developing AD through more effective treatment of late-life MDD.

New York 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]

New York, New York 100165802 United States

Single Zip Code

Research on Current Topics in Alzheimer's Disease and Its Related Dementias (R01 Clinical Trial Optional) (PAR-19-070)

Amendment Since initial award the total obligations have increased 392% from $785,139 to $3,865,122.