Cognitive impairment in ICU survivors: Assessment and therapy

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The cognition-focused intervention most often described is cognitive training. Cognitive training is delivered in individual or group sessions in which the patient practices tasks targeting different domains, such as memory, language, and attention. Outcomes are often assessed in terms of improvement in test scores or effects on everyday functioning. Unfortunately, because of heterogeneity among cognitive training interventions and studied populations, we cannot yet make strong evidence-based recommendations for clinical practice.

Martin et al56 in 2011 reviewed cognition-based interventions for healthy older people and people with mild cognitive impairment and found 36 relevant studies. Of these, only 3 were in patients with mild cognitive impairment, while the rest were in healthy older people.56–58 Overall, the only available data were related to the memory domain, and outcomes were mostly associated with immediate recall of words, paragraphs, and stories. Based on this, cognitive therapy is currently considered justified, as most patients with cognitive impairment after an ICU stay have memory problems.

Zelinski et al59 conducted a randomized, controlled, double-blind study comparing outcomes in an intervention group that underwent a computerized cognitive training program with those in a control group that viewed videos on a variety of topics such as literature, art, and history. The intervention, based on brain plasticity, aimed to improve the speed and accuracy of auditory information processing and to engage neuromodulatory systems. Some of the secondary outcomes favored the intervention group. These outcomes were related mostly to measures of overall memory, such as immediate and delayed recall, but also to a composite outcome that included letter-number sequencing and the digit span backwards test.

Despite these encouraging results, it is worth mentioning that these studies were not performed in patients with cognitive impairment associated with ICU admission. Therefore, the applicability and effectiveness of such therapies in post-ICU patients remains unknown.

Patients with posttraumatic brain injury and stroke have also been extensively studied in regard to the development of cognitive impairment.34 These patients probably represent a better standard for comparison, as their cognitive impairment does not necessarily progress.

The effect of cognitive rehabilitation on the recovery in these patients depends on adaptation and remediation. Adaptation describes a patient’s ability to compensate for functional impairment.34 This can be divided into internal and external adaptation. Internal adaptation requires the patient to recognize his or her cognitive limitation in order to adapt the to the environment accordingly. External adaptation entails getting help from devices or relatives (eg, phone calls) to achieve desired goals (eg, taking medication at scheduled times). Again, to adapt, the patient needs to be able to recognize his or her affected cognitive domain. Unfortunately, this is not always the case.

Remediation refers to the actual regaining of a lost ability. To stimulate neural plasticity, the patient is required to experience and repeat targeted skill-building activities.38 There is evidence that patients are more likely to regain lost ability by repeating the practice frequently during a short period of time.60

From the physician’s perspective, evaluating and identifying deficits in particular cognitive domains may help in designing a remediation plan in partnership with a cognitive therapist.

Cognitive rehabilitation in ICU survivors

The Returning to Everyday Tasks Utilizing Rehabilitation Networks (RETURN) study focused on cognitive and physical rehabilitation in post-ICU patients.61 This pilot study included 21 ICU survivors with cognitive or functional impairment at hospital discharge. Eight patients received usual care and 13 received a combination of in-home cognitive, physical, and functional rehabilitation over a 3-month period with a social worker or a master’s-level psychology technician.

Interventions included six in-person visits for cognitive rehabilitation and six televisits for physical and functional rehabilitation. Cognitive training was based on the goal-management training (GMT) protocol.62 This strategy attempts to improve executive function by increasing goal-directed behavior and by helping patients learn to be reflective before making decisions and executing tasks. The GMT model consists of sessions that build on one another to increase the rehabilitation intensity. During each session, goals are explained and participants perform increasingly challenging cognitive tasks.

Cognitive outcomes were evaluated using the Delis-Kaplan Tower Test to evaluate executive function by assessing the ability to plan and strategize efficiently. The patient is required to move disks across three pegs until a tower is built. The object is to use the fewest moves possible while adhering to two rules: larger disks cannot be placed on top of smaller ones, and disks must be moved one at a time, using only one hand.

At 3 months there was a significant difference between groups, with the intervention group earning higher tower test scores than controls did (median of 13 vs 7.5).

The Activity and Cognitive Therapy in the Intensive Care Unit (ACT-ICU) trial is another pilot study that will attempt to assess the feasibility of early cognitive rehabilitation in ICU survivors. This study will combine early mobilization with a cognitive intervention, and its primary outcome is executive function (with the tower test) at 3 months after discharge.63


Some medications have been tested to assess whether they reduce the risk of progression from adult traumatic brain injury to cognitive impairment. These drugs augment dopamine and acetylcholine activity.

Methylphenidate (Ritalin), a dopaminergic drug, was studied in two trials. The first was a double-blind trial in 18 patients with posttraumatic brain injury. Memory was found to improve, based on the Working Memory Task Test. However, due to the small number of participants, no further conclusions were obtained.64

The second trial, in 19 patients with posttraumatic brain injury, had a double-blind crossover design. Attention, evaluated by the Distraction Task Test, improved with the use of methylphenidate.65 Again, the small number of patients precludes generalization of these results.

Donepezil (Aricept), a cholinergic drug, was evaluated in four clinical trials in posttraumatic brain injury patients66–69; each trial included 21 to 180 patients. The trials evaluated the drug’s effect on memory and attention through a variety of tools (Paced Auditory Serial Addition Test; Wechsler Memory Scale; Boston Naming Test; Rey Auditory Verbal Learning Test; Complex Figure Test; and Reaction Time–Dual Task). Interestingly, donepezil was associated with large improvements in objective assessments of attention and memory. Despite methodologic flaws, such as a lack of blinding in one of these studies69 and an open-label design in two of them,66,68 of the drugs available, donepezil presents the strongest evidence for use in cognitive impairment after traumatic brain injury.70

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