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AD-Related Dementias Focus
Advance understanding of basic mechanisms underlying neurocognitive impairment and dementia due to COVID-19 in order to develop biomarkers, risk profiles, and the foundation for early interventional trials.
2029 NOT-AG-21-016: Neurological and Neurocognitive Sequelae from SARS-CoV-2 Infection and COVID-19 in Aging and Age-Related Neurodegeneration RFA-NS-23-021: Understanding Neurological Effects of COVID-19 and Post-Acute Sequelae of SARS-CoV-2 Infection (R01 Clinical Trial Optional) PAR-23-154: Development and Validation of Models for Alzheimer’s Disease-Related Dementias (ADRD) (R61/R33 - Clinical Trial Not Allowed) PAR-23-214: Neuropathological Interactions Between COVID-19 and ADRD (R01 - Clinical Trial Not Allowed) PAR-24-203: Neuropathological Interactions Between COVID-19 and ADRD (R01 - Clinical Trial Not Allowed) 2.CC In Progress Understanding AD/ADRD brain changes after COVID-19 DN 2022 ADRD Summit: Multiple Etiology Dementias (MED) Special Topic: Impact of COVID-19 on AD/ADRD Risk and Outcomes Milestone 4, Priority 4 Research on Disease Mechanisms Projects funded in FY22
- At least three studies to determine basic mechanisms, potential biomarkers, and pathways with potential for therapeutic intervention, underlying increased risk of long-term cognitive impairment and dementia outcomes following COVID-19.
Summary of Key Accomplishments
A recent initiative supports research using different experimental models to investigate the basic mechanisms by which coronavirus interacts with and/or modifies ADRD-relevant phenotypes. One funded study seeks to uncover the underlying causes of enduring sensory, neurological, and cognitive symptoms that persist long after post-infection, even when inflammation subsides. This study uses an innovative transgenic mouse model and state-of-the-art genetic techniques to identify potential interventions for long COVID.
In another project, researchers at the University of Chicago are working to prevent or treat vascular dementia following SARS-CoV-2 infection. Using mechanistic mouse models, the research team is exploring how modifications to brain endothelial cells caused by the infection can promote development of vascular dementia by destabilizing the blood-brain barrier.
In other ongoing work, investigators at Louisiana State University Health Science Center at Shreveport are testing the hypothesis that SARS-CoV-2-associated inflammation promotes Lewy body pathology in the olfactory bulb which can then propagate to other regions of the brain important for cognition, potentially setting the stage for the future development of Lewy body dementia. In addition, scientists at the University of Florida are studying how residual SARS-CoV-2 spike protein in the choroid plexus (an important barrier between peripheral blood and cerebrospinal fluid in the brain) induces an aging-related phenotype known as cellular senescence that can then be propagated via cerebrospinal fluid to trigger amyloid and tau accumulation in cognitive regions of the brain.
Another group of researchers at Wake Forest University have been investigating whether SARS-CoV-2 infection in nonhuman primates causes changes in the brain that also occur with AD/ADRD and whether vaccination against the virus can prevent such changes. These investigators are assessing neuroimaging measures of brain activity associated with higher order executive function (i.e., working memory), the accumulation of blood and cerebrospinal fluid biomarkers of neurodegeneration (i.e., Aβ, Tau, GFAP, NF-L), and behavioral performance on motor and cognitive tasks at both pre- and post-infection timepoints with and without vaccination.
The key accomplishments summary is current as of September 2025.