Cognitive Changes After Major Joint Replacement - Full Trial (Cognigram 2)

Postoperative cognitive dysfunction (POCD) is thought to affect a significant proportion of patients after major surgery (up to 10% at 3 months). This is potentially a major public health issue because patients with POCD have prolonged hospital admission, loss of independence and mortality. Undoubtedly, if POCD is as prevalent and devastating as has been previously reported, the decision to undergo elective surgery should be influenced by the risk of developing POCD. Given the scope of the issue, the deficiencies in the literature surrounding POCD are concerning. There are many methodological issues with previous studies and the diagnosis of POCD in the perioperative period.

It is imperative that the true natures of postoperative cognitive changes are elucidated so that preoperative risk stratification can be appropriately determined. This will lead to care pathways and interventions that can modify any possible downward changes thereby reducing the negative impact on patients and the health care system.

Main Study Hypothesis: The incidence of postoperative cognitive changes in the joint arthroplasty population is influenced by:

1. Occurrence of major acute postoperative complications (e.g., cardiac event, pulmonary embolus, renal failure, pneumonia, prosthetic joint infection)
2. Pre-existing mild cognitive impairment (MCI)
3. Post-operative delirium
4. Pre-existing comorbid conditions with inflammatory states such as auto-immune disorders, coronary artery disease, obstructive sleep apnea, and auto-immune disorders

Study Objectives:

In patients undergoing primary total hip or knee arthroplasty the goals of this project are to:

1. Establish cognitive trajectories after major lower extremity joint arthroplasty and the incidence of both post-operative delirium and POCD
2. Test Main Study Hypothesis (see above)

• Cognitive Testing (Other): Computerized CogState Brief Battery (CBB), Cognigram, assesses changes in four cognitive domains including psychomotor function, attention, learning and memory, and working memory. The CBB is a computerized test based on card games that can be administered online

Primary outcomes

• Proportion of patients with Cognigram score decreasing by > 2 SDs from baseline at 4.5 [4.5 months from baseline]: Proportion of patients with Cognigram score decreasing by > 2 SDs from baseline at 4.5

Secondary outcomes

• Proportion of patients with Cognigram score decreasing between 1 and 2 standard deviations from baseline at 4.5 months [4.5 months from baseline]: Proportion of patients with Cognigram score decreasing between 1 and 2 standard deviations from baseline at 4.5 months
• Effect of pre-operative MCI on postoperative cognitive changes at 4.5 months [4.5 months from baseline]: Effect of pre-operative MCI on postoperative cognitive changes at 4.5 months
• Effect of pre-operative chronic inflammatory states on postoperative cognitive changes at 4.5 months [4.5 months from baseline]: Effect of pre-operative chronic inflammatory states on postoperative cognitive changes at 4.5 months
• Effect of postoperative delirium on postoperative cognitive changes at 4.5 months [4.5 months from baseline]: Effect of postoperative delirium on postoperative cognitive changes at 4.5 months
• Effect of postoperative complications on postoperative cognitive changes at 4.5 months [4.5 months from baseline]: Effect of postoperative complications on postoperative cognitive changes at 4.5 months

Sex: All, ages: 50 Years to any

Inclusion Criteria:

* All patients ≥ 50 years of age undergoing elective total hip or knee arthroplasty at Sunnybrook Health Sciences Centre

Exclusion Criteria:

* Lack of informed consent
* Inability to comply with study procedures or follow-up visits
* Patients with diagnosed dementia or those being treated with donepezil (Aricept®)
* Patients with severe cognitive impairment defined as baseline with a CBB score of equal to or less than 80 in at least one of the 4 CBB domains
* Patients with uncontrolled psychiatric diagnoses including schizophrenia, bipolar disorder, major depressive mood disorder
* Patients undergoing a second joint replacement \& previously enrolled in this study within the past 6 months

• Results publication: Choi S, Avramescu S, Orser BA, Au S. Protocol for a prospective cohort study of assessing postoperative cognitive changes after total hip and knee arthroplasty in the Greater Toronto area. BMJ Open. 2019 Feb 24;9(2):e024259. doi: 10.1136/bmjopen-2018-024259. PMID 30804030

• Stephen Choi, MD,FRCPC,MSc, Principal investigator, Sunnybrook Research Institute