Inability to recruit during COVID-19

The long-term goal of this research program is to improve understanding of the mechanistic link between Alzheimer's disease (AD) neuropathology, acute delirium, and cognitive impairment following acute respiratory failure. In this pilot study, the study team will establish a prospective cohort of older patients with acute respiratory failure and obtain data on delirium duration, AD imaging and CSF biomarkers, and cognitive outcomes following critical illness.

The study team will recruit patients with no known history of dementia for enrollment into the cohort during their hospital stay for acute respiratory failure. The cohort will undergo testing including cognitive testing, MRI imaging, lumbar puncture for cerebrospinal fluid (CSF) analysis at 3 months following hospital discharge. The study will examine the association of delirium duration during the hospital stay and cognitive impairment at 3 month follow-up with CSF levels of amyloid- β42, tau, and phospho-tau. Measures of delirium will also be related with structural/functional MRI dependent measures. The goal is to design a larger prospective cohort study to evaluate the relationship between AD imaging and CSF biomarkers with delirium and post-ICU cognitive impairment. The results of this pilot study with provide important information with regard to future study design including: (1) ratio of eligible to recruited patients (2) retention rate; (3) safety and feasibility of protocol; and (4) preliminary effect size estimates.

Inclusion Criteria:

• Age greater than or equal to 55 years
• Anticipated ICU stay of at least 48 hours
• Delirium during ICU stay defined as CAM-ICU positive on at least two occasions at least 12 hours apart within 72 hours.

Exclusion Criteria:

• Diagnosis of dementia in electronic medical record at time of ICU admission
• Blindness, deafness, or inability to understand English as this prevents ICU delirium assessment
• Cognitive impairment prior to hospitalization (inability to follow instructions/comply with study/sign consent)
• Score of > 3.30 on Informant Questionnaire of Cognitive -Decline in the Elderly (IQCODE)[34]. Questionnaire will be given to family member or legally authorized representative.
• Pregnancy/lactating/breastfeeding
• Legally incapacitated: Prisoner/Ward of State
• History of prior large vessel cerebrovascular accident (CVA)
• History of neurologic disorder prior to ICU admission including multiple sclerosis, Parkinson disease, epilepsy, amyotrophic lateral sclerosis (ALS), Guillain-Barre Syndrome (GBS)
• Psychiatric illness including schizophrenia, bipolar disorder, depression with psychotic features
• Not expected to survive 24 hours
• Judgment of investigator that subject participation could jeopardize subject health/safety or integrity of study
• Active malignancy requiring treatment in the prior 6 months
• Inability to return for study procedures
• Inability to obtain consent

We propose to recruit older patients with acute respiratory failure requiring mechanical ventilation admitted to the medical ICU of an academic medical center, Wake Forest Baptist Hospital.