R01AG077422

Alzheimer's Disease Related Biomarkers Following SARS-CoV-2 Infection - Abstract

Cognitive impairment is a major symptom among patients with post-acute sequelae of COVID-19. Older individuals and those with dementia risk factors are particularly at risk.

In our own prospective study of 4,491 hospitalized COVID-19 patients, the median age was 65 years. 606 (14%) developed new neurological disorders (most commonly encephalopathy) during hospitalization, indicating a population at high risk for development of Alzheimer's disease or related-dementia (AD/ADRD).

Of this group, 48% of patients who were cognitively normal pre-COVID had abnormal telephone MOCA scores (<18) 6-months post hospital discharge. We identified significant elevations in plasma biomarkers of neurodegeneration/AD including total tau, p-tau-181, UCH-L1, neurofilament light chain (NFL), and GFAP in hospitalized COVID-19 patients who developed encephalopathy compared to those who did not. These biomarkers significantly correlated with IL-6, CRP, ferritin, and D-dimer measures of inflammation.

We hypothesize that older subjects with COVID-19, in particular those with new post-COVID subjective or objective cognitive abnormalities, will have increased plasma and radiographic AD/ADRD biomarkers, and a greater likelihood of abnormal cognitive testing and progression to Alzheimer's disease or related dementias over time.

We will enroll 3 groups of patients aged ≥60 years including:
1) SARS-CoV-2 positive subjects who have new subjective or objective cognitive symptoms ≥6 months from index SARS-CoV-2 infection (COVID+COG+)
2) SARS-CoV-2 positive subjects without subjective or objective cognitive symptoms ≥6 months from infection (COVID+COG-)
3) SARS-CoV-2 negative, neurologically/cognitively normal subjects, enrolled in the NYU ADRC Clinical Core (controls).

We will exclude individuals with a history of MCI or AD/ADRD prior to SARS-CoV-2 infection. Our primary outcome will be the differences in trajectories of global cognition/function (Clinical Dementia Rating Scale Sum of Boxes [CDR-SB]) over the 5-year study across the 3 groups. Secondary outcomes will include: differences in plasma and radiographic AD/ADRD biomarkers over time compared across the 3 groups.

Aim 1: Characterize and compare cognitive and neuropsychological abnormalities at enrollment and over time (every 12 months), among COVID+COG+, COVID+COG-, and controls using the CDR-SB, and Uniform Data Set Version 3.

Aim 2: Characterize and compare plasma AD/ADRD-related biomarkers of neurodegeneration, inflammation, and BBB dysfunction at enrollment and over time (every 12 months), among COVID+COG+, COVID+COG-, and controls.

Aim 3: Characterize and compare AD/ADRD neuroimaging biomarkers in COVID+COG+, COVID+COG-, and controls at enrollment and over time (every 18 months) using 3T MRI.

Collectively, these studies will elucidate predisposing risk factors and biomarkers for COVID-related cognitive abnormalities, provide mechanistic insights into underlying pathogenesis, and provide data on long-term outcomes, including the development of AD/ADRD-related disorders.

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 100166066 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 300% from $1,378,414 to $5,518,240.