R56AG074467

SARS-CoV-2 and Precursors of Alzheimer's Disease and Related Dementias: An Ultrahigh Field (7T) MRI Study in a Diverse Multinational Cohort

The SARS-CoV-2 virus has shown neurotropism in some infected patients, with reports of viral invasion, inflammation, meningoencephalitis, microvascular injury, stroke, delirium, and delayed cognitive and psychiatric symptoms. However, it is still unclear whether there is any acceleration of neurodegenerative processes and an increased risk of Alzheimer's disease and related dementias (ADRD).

Race, ethnic minorities, and men are known to have a higher risk of dying from COVID-19 and may also have a greater susceptibility to long-term neuropsychiatric sequelae.

Ultrahigh field (7T) MRI has increased sensitivity and spatial resolution compared to 3T MRI, allowing for the detection of small changes in cortical and white matter structure, integrity and connectivity, inflammation, iron deposition, hippocampal subfields, venular injury, and the locus coeruleus.

The 7T MRI COVID Consortium is an international collaboration across five sites, aiming to enroll a diverse, multi-ethnic cohort of 780 persons aged 55-80. Among these, 260 persons will have well-documented SARS-CoV-2 infection (cases), and 260 will be 'illness' controls with a clinically similar non-COVID illness (e.g., pneumonia). Both groups will include over 25% Hispanic and over 25% African-Americans. Additionally, 260 healthy controls with documented normal cognition and no hospitalization in the preceding two years will be included.

Data will also be drawn from 40 persons with autosomal dominant early-onset AD and 180 population controls, all imaged with the same 7T MRI protocol. All participants will undergo two annual 7T MRI scans and four detailed exams comprising neurological, cognitive, and psychiatric assessments, smell and gait evaluations, blood biomarkers of neurodegeneration (P-TAU181, NFL, GFAP, amyloid), systemic inflammation markers (CRP, IL6, IL10, TNF-alpha, IL1R), and surveillance for incident mild cognitive impairment (MCI) and ADRD dementia. These exams will occur at the time of each MRI and at 36 and 48 months post-illness.

The study aims to achieve the following specific aims:

Aim 1: Detail the range of early (6-12 months) brain pathology in COVID survivors (Aim 1A), assess if early changes improve, persist, or worsen at a delayed 7T MRI (12-18 months) (Aim 1B), and compare findings in COVID survivors to MRI in preclinical early-onset AD (Aim 1C).

Aim 2: Compare the cross-sectional prevalence of pre-illness ADRD and vascular injury (VCID) and the cognitive, behavioral, mood, and functional outcomes across the three groups.

Aim 3: Relate early and delayed 7T MRI measures to subsequent risk of MCI, dementia, and cognitive and gait trajectories.

Aim 4: Explore if race/ethnicity, sex, blood biomarkers, genetics, or early SARS-CoV-2 'treatments' are effect-modifiers, mediators, or neither of the associations noted in Aims 1-3.

The investigators leading this grant are also members of other larger, less detailed COVID consortia, allowing for harmonized data analyses. This study aims to provide a better biological understanding of the mechanisms and modifiers of long-term neurological and psychiatric sequelae of COVID-19. It could also help illuminate the role of viral infections, inflammation, and immune response in ADRD.

The University Of Texas Health Science Center At San Antonio

NOT APPLICABLE

93.866 - Aging Research

National Institute on Aging (NIA) [HHS - NIH]

San Antonio, Texas 782293900 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 End Date has been extended from 08/31/22 to 08/31/25.