BRAIN-2 COVID-19 Administrative Supplement (2)

The NIA-funded BRAIN-ICU-2 Study [Bringing to light the Risk factors And Incidence of Neuropsychologicaldysfunction (dementia) in ICU Survivors, 2nd Study] will define the relationship between ICU delirium anddementia. The proposed administrative supplement to BRAIN-ICU-2 Study (R01 AG58639) is in response toNIA Availability of Administrative Supplements and Revision Supplements on Coronavirus Disease 2019(COVID-19) (NOT-AG-022; PA-18-591). To understand the brain tissue damage of acute delirium caused bySevere Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), we will perform new neuropathologicalstudies of critically ill patients affected by COVID-19, as well as those with Alzheimer's disease and relateddementia (ADRD) with/without critical illness. By studying COVID-19, we will better understand the relationshipbetween delirium and ADRD. During the current COVID-19 pandemic, intensive care units (ICU's) across thenation are awash with patients experiencing delirium, a major ICU risk factor for future ADRD. These deliriumsymptoms of impaired consciousness include headache, alteration of gustatory, olfactory, and visual function,neuropathy, seizures, agitation, encephalitis, and/or Guillain-Barre syndrome. These delirium signs andsymptoms could be due to SARS-CoV-2 infection of the brain, particularly in those with ADRD. We do notknow if there are direct nervous system consequences of COVID-19 (e.g., inflammation), and/or indirectnervous system consequences, e.g., coagulopathy. To our knowledge, limited autopsy series that includedbrain tissue have been published. No information about ADRD was provided. The proposed supplement willspecifically compare multiple groups of patients, ICU patients with/without ADRD with/without COVID-19, alongwith non-ICU patients with/without ADRD and with/without COVID-19. The BRAIN-ICU-2 study will provide ICUpatients with/without ADRD with/without COVID-19. The NIA-supported Religious Orders Study (ROS; P30AG10161, R01 AG15819), and Rush Memory and Aging Project (MAP; R01 AG17917) will provide non-ICUpatients with/without ADRD and with/without COVID-19. The proposed supplement will further build oncollaboration between the Vanderbilt and Rush BRAIN-ICU-2 study teams, and represent the mostcomprehensive neuropathologic examination of COVID-19 brains compared to non-COVID-19 brains, in thosewith/without ADRD, and with/without critical illness. This supplement will create a unique resource for theworld-wide COVID-19 research community, with a strong and sustained impact on the fields of ICU deliriumand ADRD.