The NIA-funded BRAIN-ICU-2 Study [Bringing to light the Risk factors And Incidence of Neuropsychological dysfunction (dementia) in ICU Survivors, 2nd Study] will define the relationship between ICU delirium and dementia. The proposed administrative supplement to BRAIN-ICU-2 Study (R01 AG58639) is in response to NIA 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 by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), we will perform new neuropathological studies of critically ill patients affected by COVID-19, as well as those with Alzheimer’s disease and related dementia (ADRD) with/without critical illness. By studying COVID-19, we will better understand the relationship between delirium and ADRD. During the current COVID-19 pandemic, intensive care units (ICU’s) across the nation are awash with patients experiencing delirium, a major ICU risk factor for future ADRD. These delirium symptoms of impaired consciousness include headache, alteration of gustatory, olfactory, and visual function, neuropathy, seizures, agitation, encephalitis, and/or Guillain-Barre syndrome. These delirium signs and symptoms could be due to SARS-CoV-2 infection of the brain, particularly in those with ADRD. We do not know if there are direct nervous system consequences of COVID-19 (e.g., inflammation), and/or indirect nervous system consequences, e.g., coagulopathy. To our knowledge, limited autopsy series that included brain tissue have been published. No information about ADRD was provided. The proposed supplement will specifically compare multiple groups of patients, ICU patients with/without ADRD with/without COVID-19, along with non-ICU patients with/without ADRD and with/without COVID-19. The BRAIN-ICU-2 study will provide ICU patients with/without ADRD with/without COVID-19. The NIA-supported Religious Orders Study (ROS; P30 AG10161, R01 AG15819), and Rush Memory and Aging Project (MAP; R01 AG17917) will provide non-ICU patients with/without ADRD and with/without COVID-19. The proposed supplement will further build on collaboration between the Vanderbilt and Rush BRAIN-ICU-2 study teams, and represent the most comprehensive neuropathologic examination of COVID-19 brains compared to non-COVID-19 brains, in those with/without ADRD, and with/without critical illness. This supplement will create a unique resource for the world-wide COVID-19 research community, with a strong and sustained impact on the fields of ICU delirium and ADRD.

PROJECT NARRATIVE The NIA BRAIN-ICU-2 study will define the relationship of intensive care unit-related delirium to the development of Alzheimer’s disease and related dementia (ADRD). To understand the brain tissue damage of acute delirium caused by SARS-CoV-2, we will perform new neuropathological studies of critically ill patients affected by COVID-19, as well as those with ADRD with/without critical illness. By studying COVID-19, we will better understand the relationship between delirium and ADRD.