Improving the Recovery and Outcome Every Day After the ICU

Critical illness has deleterious consequences on both acute and chronic cognitive functions.
Acute cognitive dysfunction manifests itself as delirium in the critically ill especially the
elderly. Delirium is a complex neuropsychiatric syndrome characterized by acute and
fluctuating changes in cognition and consciousness. 60% to 80% of critically ill ventilated
older patients and 30% to 50% of those with less illness severity have delirium for at least
one day of their ICU or hospital stay. Chronic cognitive dysfunction manifests as ICU
acquired cognitive impairment and dementia after critical illness, affects multiple cognitive
domains and persists years after hospital discharge. Up to 71% of critical illness survivors
have cognitive impairment at one year after hospital discharge and close to 18% are diagnosed
with new dementia including Alzheimer's disease within three years post ICU hospitalization.

Two million older Americans suffer from an episode of delirium during their intensive care
unit (ICU) stay. Presence of delirium predisposes the elderly to immediate in-hospital
complications including a longer length of ICU and hospital stay, increased risk of
in-patient mortality and elevated costs of care. In addition, ICU delirium is associated with
long-term post-discharge complications such as development of cognitive impairment and
dementia. Current advances in the management of critical illness have notably improved the
survival rates among this vulnerable segment of older adults. However, increased survival
comes at a cost with as many as 70% of older ICU survivors who had an episode of delirium
suffering from subsequent cognitive impairment and dementia. At present, there are no
effective and scalable recovery models to remediate ICU acquired cognitive impairment and its
attendant elevated dementia or Alzheimer's disease risk.

The inability to develop efficacious interventions to reduce ICU acquired cognitive
impairment may stem from a limited understanding of the link between acute brain dysfunction
(delirium) and chronic brain dysfunction (ICU acquired cognitive impairment, dementia or
Alzheimer's disease). The investigators propose a recovery intervention guided by the
pathophysiologic mechanisms implicated in producing critical illness delirium and elevated
risk of cognitive impairment. The intervention targets inflammation, glial dysfunction and
astrocyte activation along with restoration of neurotrophic factors while training function
directly across multiple cognitive domains to reduce the burden of cognitive impairment among
ICU survivors of delirium.

Over the past five years, Indiana University Center for Aging Research has developed a
research infrastructure focused on delirium and delirium associated cognitive impairment,
encompassing the ICU and post-ICU periods. This includes developing a bio-repository of serum
delirium biomarkers, ICU based delirium trials, and post-ICU exercise and cognitive therapy
recovery models. Building upon prior work and based on the pathophysiologic mechanisms
mentioned above, the investigators now propose a novel home-based combined physical exercise
and cognitive training program for older ICU survivors to improve cognitive impairment.

The study team is proposing a 2x2 factorial design randomized controlled trial (RCT) called
"Decreasing Alzheimer's Disease and Related Dementias after Delirium-Exercise and Cognitive
Training (DDD-ECT)" to evaluate the efficacy of 12 weeks of combined physical exercise and
cognitive training on the primary outcome of cognitive function among older ICU survivors who
experienced delirium or subsyndromal delirium during their ICU stay. The investigators
propose to deliver these interventions via a facilitator-led, small group format using
internet-enabled, multiparty-videoconference delivered directly into the participants' homes
to achieve the study aims listed in the summary.

Inclusion Criteria:

- Patients aged ≥ 50 years

- Admitted to medical and/or surgical ICUs at Methodist, University, or Eskenazi
hospitals

- Discharged home or to sub-acute rehabilitation, long-term acute care, or skilled
nursing facility

- Able to provide consent or has a legally authorized representative to provide consent

- Access to a telephone (study provides computer and broadband)

- Have at least one episode of subsyndromal delirium or delirium as determined by the
Confusion Assessment Method for the ICU-7 (CAM-ICU).

Exclusion Criteria:

- Diagnosis of cancer with short life expectancy

- Current chemotherapy or radiation therapy (confirmed by electronic medical record)

- History of dementing illnesses and other neurodegenerative disease such as Alzheimer's
disease, Parkinson disease, or vascular dementia (confirmed by EMR), or current
prescription of anti-dementia medication, or ruled out by Functional Activities
Questionnaire (FAQ) score defining dementia

- History of bipolar disorder or schizophrenia (confirmed by EMR)

- Current alcohol consumption > 5 drinks per day (self reported and/or confirmed by EMR)

- Vision < 20/80 via Snellen card or confirmed by EMR

- Low hearing or communicative ability (examiner rated) that would interfere with
interventions and outcome assessments

- Have any active and untreated American College of Sports Medicine absolute
contraindications to exercise (confirmed by EMR) including: acute myocardial
infarctions within the past 2 days, ongoing unstable angina, uncontrolled cardiac
arrhythmia with hemodynamic compromise, active endocarditis, symptomatic severe aortic
stenosis, decompensated heart failure, acute pulmonary embolism, pulmonary infarction,
or deep venous thrombosis, acute myocarditis or pericarditis, acute aortic dissection,
physical disability that precludes safe and adequate testing, or are unable to obtain
provider clearance for physical exercise for any contraindication where medical
management is unclear

- Have any active and untreated American College of Sports Medicine relative
contraindications to exercise (confirmed by EMR) including: known obstructive left
main coronary stenosis, moderate to severe aortic stenosis with uncertain relationship
to symptoms, tachydysrhythmias with uncontrolled ventricular rates, acquired advanced
or complete heart block, recent stroke or transient ischemia attack, mental impairment
with limited ability to cooperate, resting hypertension with systolic >200 mm Hg or
diastolic >100 mm Hg, uncorrected medical conditions, such as significant anemia,
important electrolyte imbalance, and hyperthyroidism, or are unable to obtain provider
clearance for physical exercise for any contraindication where medical management is
unclear

- Recovering from a skeletal fracture (confirmed by EMR), unless cleared by their
physician of record to safely participate in exercise

- Acquired neurologic injury (stroke, traumatic brain injury, cerebral edema/swelling,
anoxic brain injury, or any other acute/subacute severe neurologic deficit) as the
admitting diagnosis or a new event during the course of hospitalization (confirmed by
EMR)

- History of drug abuse within the last 3 months confirmed by EMR or self-report with
Drug Abuse and Screening Test (DAST-10) score ≥ 3

- Have any spinal cord injury with persistent neurologic deficit at the time of study
enrollment

- Status post tracheostomy and not eligible for a speaking valve

- Pregnant or nursing

- Incarcerated or homeless at time of study

- Lives outside the greater Indianapolis area