Cognitive Training for the Prevention of Postoperative Delirium

Postoperative delirium is a significant public health concern, affecting up to 70% of elderly patients presenting for surgery. Furthermore, postoperative delirium is associated with increased mortality, persistent cognitive decline, increased hospital length of stay, and elevated healthcare costs. Unfortunately, there is a lack of evidence-based strategies that consistently and effectively reduce the risk of delirium. In fact, although the American Geriatrics Society has released guidelines for the prevention of postoperative delirium, the evidence supporting many of the proposed preventive measures has been deemed low quality. Cognitive training exercises have been shown to improve cognitive function and functional status in community-dwelling elderly adults, and benefits may last for several months to years. Specifically, training exercises have led to improved performance in attention, short-term memory, and visuospatial processing; all of which are implicated as clinical features of delirium. Cognitive training has also strengthened connectivity in brain networks implicated in postoperative delirium. Thus, given these specific neurological benefits afforded, preoperative cognitive training may provide protection against the development of postoperative delirium. As such, the aim of this pilot study is to assess the feasibility of implementing a preoperative cognitive training program for surgical patients at high-risk for delirium and other associated complications.

This will be a single-center study conducted at the University of Michigan Health System. Participants will be prospectively enrolled and randomized to the interventional group (cognitive training) or control group (no training). Recruitment will take place at the University of Michigan Domino's Farms preoperative clinic at least seven days prior to scheduled, elective surgery. The recruitment goal will be 30 patients per group (total N=60) in this feasibility study. A computer-generated, stratified randomization schedule will be utilized. This study will use an adaptive cognitive training battery that specifically targets attention, working memory, and visuospatial processing (BrainHQ, Posit Science Corporation, San Francisco, CA). These tests have been successfully used across diverse patient populations, demonstrating improvements in cognition and functional outcomes to varying degrees. The level of difficulty of each test is automatically adjusted depending on the participant's performance, with test difficulty increasing as user performance improves. Participants will access the training software platform via home internet connection, and our study team will be able to monitor training progress. Delirium assessments will be performed using the Confusion Assessment Method, 3-minute diagnostic assessment (3D-CAM) or CAM-ICU as appropriate, and they will take place at baseline, in the postanesthesia recovery unit (PACU), and twice daily from postoperative day (POD) 1-3. The assessor performing the CAM interviews will be blinded to the intervention. Our team has completed formal training in CAM methodology through the NIH-funded (K07AG041835) Center of Excellence for Delirium in Aging: Research, Training, and Educational Enhancement (CEDARTREE) at Beth Israel Deaconess Hospital, Boston, MA. Cognitive function will be briefly assessed throughout the study period using three tests from the NIH Toolbox Cognition Battery - Flanker Inhibitory Control and Attention Test, List Sorting Working Memory Test, and the Pattern Comparison Processing Speed Test. Collectively, these tests assess executive function, attention, working memory, and processing speed, which are cognitive domains affected by delirium as described above. These tests have been validated in adults up to the age of 85, and they will be administered, via calibrated iPad, to participants at baseline, the morning of surgery, and at the conclusion of the POD3 visit. The purpose of this testing will be to assess for sustained, transferred, cognitive gains afforded by training in the intervention group. Delirium is a grave public health concern, particularly for surgical patients. Cognitive training has shown promise with improving clinical and neurophysiological traits associated with delirium, though this potential efficacy has not been tested in a preventive manner in vulnerable surgical patients. Cognitive prehabilitation, via targeted cognitive training exercises, may serve as feasible strategy for reducing the risk of delirium its and associated morbidity and mortality.

Patients will engage in a daily preoperative cognitive training battery (BrainHQ, Posit Science) that aims to improve attention, memory, and visuospatial processing.

Patients will not undergo preoperative cognitive training. Patients will receive standard preoperative care.

Patients will engage in a daily preoperative cognitive training battery (BrainHQ, Posit Science) that aims to improve attention, memory, and visuospatial processing.

Each participant who has experienced at least one episode of delirium by the postoperative day 3 time point, as determined by daily Confusion Assessment Method (CAM) screening, will then be calculated in each group to provide delirium incidence (%).

The Flanker Inhibitory Control and Attention Test from the NIH Toolbox Cognition Battery will be used to assess attention and focus in each study group. Uncorrected standard score (n, 0-10, 0 = no correct answers, 10 = all items answered correctly and with median reaction time 500 milliseconds or faster on each trial) will be reported within individuals to assess for cognitive function change throughout the study period.

The List Sorting Working Memory Test from the NIH Toolbox Cognition Battery will be used to assess working memory in each study group. Uncorrected standard score (n, 0-26, 0=no items correctly recalled and sequenced, 26=all items correctly recalled and sequenced) will be reported within individuals to assess for cognitive function change throughout the study period.

The Pattern Comparison Processing Speed Test from NIH Toolbox Cognition Battery will be used to assess brain processing speed in each group. Uncorrected standard score (n, 0-130, 0=no items answered correctly , 130=all items answered correctly) will be reported within individuals to assess for cognitive function change throughout the study period. Age-adjusted and fully adjusted scaled scores (n) will also be reported

Length of hospital stay (n = number of days through study completion, up to 30 days) will be assessed in each group

Length of ICU stay (n = number of days through study completion, up to 30 days) will be assessed in each group

Percentage (%) of prescribed PT sessions participants are able to successfully complete during the first week after surgery

Inclusion Criteria: Patients 60 years of age and older Major noncardiac, non-major vascular, non-intracranial surgery Daily access to computer and internet use prior to surgery Exclusion Criteria: Pre-existing cognitive impairment (preoperative delirium and/or not having capacity to provide informed consent) Severe auditory or visual impairment Emergency surgery No daily computer and internet access Already participating in cognitive training exercises

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