The overall goal of Project 3 is to discover neural signatures of COVID-19-associated cognitive impairment at the group-contrast level using volumetric, surface-based, and tract-based metrics. The overall hypothesis is that COVID-19-associated dementia will exhibit unique neural signatures discoverable through multi-modality neuroimaging.
We employ group-wise analytic strategies measuring: 1) gray-matter functional alterations using functional MRI (fMRI); 2) gray-matter atrophy using structural MRI (sMRI); and, 3) white-matter abnormalities using sMRI. Preliminary data (de Erasquin et al., in review) indicate that ~50% of post-COVID-19 enrollees over 60 years of age will be cognitively impaired, providing a balanced sample (demented:non-demented∷1:1). It is known that changes will be chronic – lasting at least 6 months – but it is not yet known whether cognitive impairment will be recuperative, progressive, or mixed.
Gray-matter Functional Signature & Connectomics. Gray-matter functional alterations will be evaluated using voxel-based physiological (VBP) metrics computed from BOLD fMRI times series. BOLD-based VBP metrics will be supplemented by fMRI blood flow (BF) in all cohorts and PET measures of glucose metabolic rate (MRglu) in the Texas cohort, for cross validation. Connectomic alterations will be assessed by group independent components analysis (GICA) and structural equation modeling (SEM) of T2* BOLD time series.
Gray-matter Structural Signature. Gray-matter structural alterations (atrophy and hypertrophy) will be evaluated using both volumetric and surface-based analyses.
White-matter Structural Signature. White matter integrity will be evaluated using tract-based, volumetric and lesion-counting analytics. Aim 4 Exploratory analyses. Features discovered through group-wise contrasts (Aims 1-3) will be tested for overlap with known patterns (e.g., AD/MCI, healthy aging, metabolic syndrome, immune mediated, etc.). They will also be tested at the per-subject level as predictors of group membership (COVID +/-; cognitive impairment +/-) and co-analyzed as quantitative biomarkers and endophenotypes with Projects 1 and 2.
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.