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Original Investigation
November 11, 2020

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

Author Affiliations
  • 1Department of Anesthesiology, The Ohio State University Wexner Medical Center, Columbus
  • 2Renaissance School of Medicine, Department of Anesthesiology, Stony Brook University, Stony Brook, New York
  • 3Boonshoft School of Medicine, Wright State University, Dayton, Ohio
  • 4Department of Psychiatry and Behavioral Health, The Ohio State University Wexner Medical Center, Columbus
  • 5Department of Orthopaedics, The Ohio State University Wexner Medical Center, Columbus
  • 6Department of Biomedical Informatics, The Ohio State University College of Medicine, Columbus
JAMA Surg. 2021;156(2):148-156. doi:10.1001/jamasurg.2020.4371
Key Points

Question  Does preoperative cognitive exercise reduce the incidence of postoperative delirium in older adults undergoing major noncardiac surgery?

Findings  Results of this randomized clinical trial show patients who met at least minimum compliance with a preoperative cognitive exercise intervention had a significantly decreased incidence of postoperative delirium.

Meaning  Modification of postoperative delirium risk with brain exercise remains a novel concept in the early stages of clinical study, and more investigation appears warranted based on this work, including investigation into the ideal activities, timing, and effective dosage.


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

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