Abstract Text

Of the millions of patients who live through critical illness annually, Intensive Care Unit (ICU) survivorship is marked by a dementia-like brain injury called post-ICU long-term cognitive impairment (ICU-LTCI) that creates grave difficulties with managing medications, handling finances, living independently, and maintaining employment. Data from our group and others show that 50% of ICU survivors suffer from ICU-LTCI and that the number of veterans who develop ICU-LTCI is as high as the number of patients with new traumatic brain injury diagnoses among all Active Duty, National Guard, and Reserves. Our pilot randomized “Returning to Everyday Tasks Utilizing Rehabilitation Networks-I” (RETURN-I) study showed that a 12-week cognitive rehabilitation intervention (versus controls) improved executive dysfunction. We then transformed this non-computerized resource- intensive strategy into a novel, efficient, and scalable Computerized Cognitive Rehabilitation (CCR) approach. This plasticity-based adaptive CCR was applied to ICU survivors enrolled in our uncontrolled case-series (RETURN-II) that signaled improvements across multiple cognitive domains. Building on nearly two decades of aging brain research with the VA-Tennessee Valley Healthcare System Geriatric Research, Education and Clinical Center (VA-TVHS GRECC), we propose this randomized controlled trial to investigate the efficacy of CCR for survivors with ICU- LTCI. The RETURN-III Study will be the next logical data-driven approach to create real-world solutions for Veterans and civilians surviving critical illness with disabling ICU-LTCI. The RETURN-III Study will test the hypotheses that a 12-week CCR intervention in medical and surgical ICU survivors will reduce the severity of cognitive impairment (Aim 1), and result in Magnetic Resonance Imaging (MRI) changes of decreased brain atrophy, greater functional connectivity, and greater cerebral blood flow (Exploratory Aim 2). To test these hypotheses, the RETURN-III study will randomize  medical and surgical VA ICU survivors with documented ICU-LTCI up to 14 days post-hospital discharge to either 12-weeks of intervention using CCR vs. control of non-specific computer games. At 3, 6, and 12 months post-randomization, trained research personnel blinded to group assignment will use a validated battery to assess global cognition [primary outcome] (Aim 1: domains of processing speed, working memory, episodic memory, executive function), and to investigate 12-month MRI imaging metrics [exploratory outcome] (Aim 2: standard structural and anatomic protocols, baseline blood oxygenation level dependent responses, pseudo-continuous arterial spin labeling).

Public Health Relevance Statement

Millions of patients survive care in medical and surgical Intensive Care Units (ICUs) every year, only to suffer from a new or accelerated dementia-like process, called post-ICU long-term cognitive impairment (ICU-LTCI). ICU-LTCI causes considerable problems with personal relationships, return to work, and everyday tasks, such as managing medicines and money. No treatment for these patients is currently available. Technology using computerized cognitive rehabilitation could improve ICU-LTCI by harnessing the healing potential of the brain (i.e., neuroplasticity). This intervention is scalable, portable, and economical. We will evaluate the effectiveness of computerized cognitive rehabilitation in a randomized controlled trial of 160 VA patients with ICU-LTCI. We hypothesize that this intervention could improve cognition, and brain structure shown by MRI. This research has high potential to influence rehabilitation strategies for Veteran and civilian ICU survivors.