Effect of Cognitive Prehabilitation on the Incidence of Postoperative Delirium Among Older Adults Undergoing Major Noncardiac Surgery: The Neurobics Randomized Clinical Trial

Abstract

Importance: Postoperative delirium in older adults is a common and costly complication after surgery. Cognitive reserve affects the risk of postoperative delirium, and thus preoperative augmentation of reserve as a preventive technique is of vital interest.

Objective: To determine whether cognitive prehabilitation reduces the incidence of postoperative delirium among older adults.

Design, setting, and participants: This was a prospective, single-blinded randomized clinical trial conducted from March 2015 to August 2019 at the Ohio State University Wexner Medical Center in Columbus. Patients 60 years and older undergoing major, noncardiac, nonneurological surgery under general anesthesia, with an expected hospital stay of at least 72 hours, were eligible for trial inclusion. Patients were excluded for preoperative cognitive dysfunction and active depression.

Interventions: Participation in electronic, tablet-based preoperative cognitive exercise targeting memory, speed, attention, flexibility, and problem-solving functions.

Main outcomes and measures: The primary outcome was incidence of delirium between postoperative day 0 to day 7 or discharge, as measured by a brief Confusion Assessment Method, Memorial Delirium Assessment Scale, or a structured medical record review. Secondary outcomes compared delirium characteristics between patients in the intervention and control groups.

Results: Of the 699 patients approached for trial participation, 322 completed consent and 268 were randomized. Subsequently, 17 patients were excluded, leaving 251 patients in the primary outcome analysis. A total of 125 patients in the intervention group and 126 control patients were included in the final analysis (median [interquartile range] age, 67 [63-71] years; 163 women [64.9%]). Ninety-seven percent of the patients in the intervention group completed some brain exercise (median, 4.6 [interquartile range, 1.31-7.4] hours). The delirium rate among control participants was 23.0% (29 of 126). With intention-to-treat analysis, the delirium rate in the intervention group was 14.4% (18 of 125; P = .08). Post hoc analysis removed 4 patients who did not attempt any cognitive exercise from the intervention group, yielding a delirium rate of 13.2% (16 of 121; P = .04). Secondary analyses among patients with delirium showed no differences in postoperative delirium onset day or duration or total delirium-positive days across study groups.

Conclusions and relevance: The intervention lowered delirium risk in patients who were at least minimally compliant. The ideal activities, timing, and effective dosage for cognitive exercise-based interventions to decrease postoperative delirium risk and burden need further study.

Trial registration: ClinicalTrials.gov Identifier: NCT02230605.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Humeidan received 2 years of loan repayment support from the National Institutes of Health Loan Repayment Programs and nonfinancial support from Lumos Labs Inc during the conduct of the study, as well as personal fees from Medtronic outside the submitted work. Drs Mavarez-Martinez and Bergese were employed by the Ohio State University Ohio State University Wexner Medical Center Department of Anesthesiology during the Neurobics Trial patient recruitment. Dr Mavarez-Martinez also reported grants from the Ohio State University during the conduct of the study. Dr Reyes reported nonfinancial support from Lumos Labs Inc during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.. CONSORT Diagram

Of the 699 patients eligible for screening, 322 patients provided consent and underwent screening. At this point, 54 patients were deemed ineligible, and 268 were randomized, 134 to cognitive exercise intervention and 134 to normal daily activity control (protocol in Supplement 2 includes discussion of Self-Administered Gerocognitive Evaluation [SAGE] exclusion process). Prior to surgery, 9 patients were excluded from the intervention group and 8 from the normal daily activity control group. Overall, 125 patients were analyzed for postoperative delirium in the cognitive exercise intervention group and 126 patients in the normal daily activity control. GDS indicates the Geriatric Depression Scale; MMSE, Mini-Mental State Examination.

Figure 2.. Lumosity Gameplay Distribution

Preoperative cognitive exercise times for the 125 patients randomized to intervention. Median and interquartile ranges (IQRs) for brain exercise time are 4.61 (1.31-7.40) hours. Four patients did not participate in any cognitive training, while 11 patients completed the recommended 10 hours of training.

Figure 3.. Postoperative Delirium Onset and Duration

Postoperative delirium course of the 47 patients with delirium (29 in the control group and 18 in the intervention group) as diagnosed by Confusion Assessment Method, Memorial Delirium Assessment Scale, or medical record review from postoperative days (PODs) 0 through 7.