Project 1: Longitudinal Epidemiology
Overview
Project 1 of ISAVRAD describes the longitudinal course, epidemiological risk/resiliency factors, and environmental interactions predictive of cognitive decline and progress to ADRD following SARS-CoV-2 infection in adults over 60 years of age from ancestral and admixed populations. Specifically, Project 1 longitudinally compares the rate of cognitive decline in older adults with and without exposure to SARS-CoV-2 infection (Aim 1). We hypothesize that cognitive changes will be progressive in nature and increase rates of ADRD based on Clinical Dementia Rating scores and neurocognitive performance. For the infected group, we compare outcomes by severity of COVID-19 symptoms and the presence and severity of anosmia, under the hypothesis that that hyposmia/anosmia, but not acute COVID-19 severity, predicts the presence and likelihood of progression of cognitive impairment and ADRD (Aim 2). Finally, working with the Neuroimaging, and Projects 2 and3, we identify predictors of SARS-CoV-2-induced cognitive decline. We hypothesize that specific symptoms (anosmia-hyposmia) segregate with related neuroimaging changes (in the olfactory cortical network) and risk is influenced by genetic ancestry to predict the highest risk of cognitive decline and new onset ADRD (Aim 3).
Participating Institutions
- UT Health SA
- UT Rio Grande Valley
Aim 1
Longitudinally compare the rate of cognitive decline in older adults with and without exposure to SARS-CoV-2 infection. Our preliminary data indicate that, in older adults, SARS-CoV-2 infection is commonly followed by amnestic mild cognitive impairment, emotional detachment and, less frequently, elevated mood. Anosmia and pre-morbid forgetfulness, but not COVID-19 severity, predict ongoing or worsening cognitive impairment six months after recovery. Based on these preliminary data, we hypothesize that these changes are progressive in nature and that, over the 3-year follow-up of the proposed study, will increase rates of ADRD based on Clinical Dementia Rating scores and neurocognitive performance.
Aim 2
For the infected group, compare outcomes by severity of COVID-19 symptoms and the presence and severity of anosmia. We will stratify by severity of COVID-19 symptoms using the WHO guidelines, the level of care required during the acute phase of the illness (e.g., none, minimal, ambulatory care, hospital admission, ICU/mechanical ventilation), and by presence and severity of anosmia. We hypothesize that hyposmia/anosmia, but not the severity of COVID-19 during the acute phase, predicts the presence and likelihood of progression of cognitive impairment and ADRD.
Aim 3
Identify predictors of SARS-CoV-2-induced cognitive decline. Interacting with the Neuroimaging Core and Project 2, we will use precision medicine strategies based on deep-learning to uncover multidimensional (feature-based) predictors of SARS-CoV-2 induced decline in individual cognitive domains/profiles. We hypothesize that specific symptoms (anosmia-hyposmia) will segregate with related neuroimaging changes (in the olfactory cortical network) and abnormalities in peripheral markers of Alzheimer’s disease, will predict with the highest risk of cognitive decline and new onset ADRD.
Core Leadership
- Dr. Gabriel de Erausquin – UT Health San Antonio
- Dr. Igor Zwir – UT Rio Grande Valley
Data and Resource Sharing
The AC oversees sharing study resources with external investigators, promoting collaborations. Resource transfer agreements are managed through the Data Management & Statistics Core and deposited in NIH-maintained repositories, including NACC, NCRAD, and NIAGADS.