Identifying Novel Aging Targets for Treatment of Delirium

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 65 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 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

- End stage renal disease requiring hemodialysis prior to admission

- History of cirrhosis prior to admission

- Chronic anticoagulation at the time of ICU admission. If patient is taking
anticoagulation at the time of follow-up visit for lumbar puncture, the lumbar
puncture will not be performed.

- Coagulation disorder prior to admission resulting in chronic thrombocytopenia
(platelet count < 100,000 mcL) or blood clotting disorder

- 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