POD is among the most common postoperative complications in the elderly and is associated with increased mortality, morbidity, hospital costs, and discharge to long-term care facilities. Thus, understanding its predictors and sequelae has considerable significance.
In a prediction model of delirium in hospitalized medical patients, independent predictors included older age, severe illness, dehydration, and cognitive and visual impairment.33 This model was validated in patients undergoing elective orthopedic surgery.7 Age, type of procedure, physical status, glucose and electrolyte abnormalities, and diminished functional and cognitive status were independent predictors in a model for POD in noncardiac surgical patients.6 However, these studies used global measures of cognitive status such as the MMSE. Although sufficient for dementia screening, those instruments are not designed to detect subtle cognitive changes.
We hypothesized that lower scores on sensitive neurocognitive tests predict POD, a hypothesis supported by our results. By design, no patients included in this study had clinically apparent cognitive deficits. The neurocognitive test battery used in this study was sensitive enough to detect subtle differences in a variety of cognitive domains. Although clinically normal, patients who developed POD had decreased performance on the tests compared with those who did not, despite similar educational levels and verbal intelligence and MMSE scores. We can only speculate why lower scores on the neurocognitive tests predicted POD. Whether these patients are more likely to develop clinically significant cognitive deterioration is not known. The lower scores in the POD patients may be early signs of neurodegenerative diseases. Alternatively, they simply may be indicative of diminished baseline cognitive reserve.
Two recent studies found that tests of executive function and depressive symptoms were independent risk factors for POD in noncardiac surgical patients.9,10 Although we did not find depressive symptoms to be predictive of POD in this study, participants had low levels of these at baseline. However, history of psychiatric illness was an independent risk factor for POD, and depression was the most common psychiatric diagnosis. Together, this suggests that depression indeed has predictive value for POD.
In our study, we used the SWCT and COWAT to measure executive function and the AVLT to assess verbal learning and memory. Although lower scores on the SWCT, COWAT, and all 3 portions of the AVLT were univariate predictors of POD, only the AVLTPercent Retention was an independent predictor. The AVLTPercent Retention is a measure of short-term memory. Thus, we found that memory, not executive function, is an independent risk factor for POD. Although preoperative subjective memory complaints are predictive of POD in cardiac surgical patients,34 Rudolph et al.35 reported that lower scores on formal tests of memory are not predictive in that population. We are unaware of other studies demonstrating that memory is a predictor of POD. Greene et al.9 and Smith et al.10 found that executive function predicts POD, but neither reported scores for tests of memory. In both studies, patients were considerably younger than those in our study. In the Rudolph et al. study, patients were similar in age to our cohort, but they had cardiac surgery instead of elective lower extremity joint replacement surgery. Whether age has a role in determining which neurocognitive domains are most predictive of POD is not clear. More research is needed to determine which domains of cognitive function are most important in predicting POD and whether age or other factors alter which domains are most important.
Although the neurocognitive findings are interesting, routine preoperative formal neurocognitive testing is time consuming, expensive, and requires trained personnel. A more clinically useful predictor of POD would be helpful. In this study, the preoperative ADL score was an independent risk factor for POD. ADL scores are quickly obtained via questionnaire or allied health personnel interview, and add no cost to the preoperative examination. Thus, functional status assessment during the preoperative evaluation is feasible and could contribute to preoperative risk stratification.
Although not the goal of the project, the independent risk factors for POD found in this study (age, ADL and AVLTPercent Retention scores, and history of psychiatric illness) could form the basis of a clinical prediction rule to assess the likelihood of POD. Further study would be necessary to validate the strength of this model and its applicability to other surgical populations.
The other key finding in this study is that POD does not predict diminished cognitive or functional status 3 months postoperatively. In medical patients, delirium predicts long-term cognitive and functional decline.11–15 Similarly, POD predicts persistent cognitive impairment after hip fracture surgery.36 POD also predicts functional decline in hip fracture surgery patients. For example, POD is an independent predictor of declines in ADL scores and ambulation, and of an increased likelihood of death or nursing home placement.37 However, falls leading to hip fracture are often the result of concurrent medical illness and surgery is performed urgently, both of which may affect the pathogenesis of POD.
Cognitive decline temporally related to surgery is known as POCD. POCD is a research construct with definitions that vary by type of cognitive testing, degree of decline required for diagnosis, and time course.38 These variations in methodology make comparisons across studies of POCD difficult.
The relationship between POCD and POD is unclear. The 2 entities may be a continuum of postoperative brain dysfunction wherein POD leads to POCD. Alternatively, they may be distinct and unrelated. Two studies using a z score definition of POCD have examined the relationship between POD and POCD.39,40 In both, POD was a predictor of POCD 1 week postoperatively, but not at 3 months.
In this study, changes in neurocognitive test scores 3 months postoperatively were not significantly different between patients experiencing POD and controls. This, and the studies noted above, suggest that after elective surgery, POD may not lead to POCD at 3 months postoperatively. In fact, mean neurocognitive test scores were improved 3 months postoperatively in both POD cases and controls. We cannot exclude that practice effects may have had some role in this. However, we attempted to minimize these effects by not retesting until 3 months postoperatively and, when available, using alternate test forms at follow-up. The improvement in test scores at 3 months may have also been influenced by the timing of preoperative testing. This was usually accomplished the day before surgery. It is possible that presurgical anxiety may have resulted in poorer performance at that time.41
In normal subjects, higher levels of educational attainment are protective against cognitive decline and dementia.42 However, higher levels of educational attainment may39 or may not43 be protective against POCD 3 months postoperatively. The participants in our study were relatively highly educated compared with those in other studies. We excluded the possibility that this had some role in our inability to find a difference in neurocognitive test scores between baseline and 3 months postoperatively in POD patients versus controls.
POD also did not affect functional status 3 months postoperatively. This, combined with the neurocognitive data, suggests that, unlike medical patients or those undergoing urgent procedures such as hip fracture repair, POD after elective surgery, once resolved, is not associated with functional decline 3 months postoperatively. Taken together, the follow-up neurocognitive and functional data suggest that, in elderly patients with good baseline functional and global cognitive status, anesthesia and elective surgery are not associated with cognitive or functional decline at 3 months.
This study has several limitations. First, it was conducted at a single institution on a homogeneous group of patients. It is unclear whether the results are generalizable to other patient populations, procedures, and institutions. However, the study design attempted to maximize the reliability of the neurocognitive and functional test results and limit confounders. One potential confounder is postoperative pain. We were not able to obtain pre- or postoperative pain scores. Pain can affect neurocognitive test scores44,45 and postoperative pain is associated with POD.46 Again, the study design attempted to account for this by including a homogeneous group of patients having similar operations. In addition, policy at our institution during the period of the study was for aggressive pain management with a goal numerical pain score of ≤3 of 10. We believe that these factors mitigated the effect of pain on the incidence of POD. Second, we developed the multivariate model using a stepwise algorithm. With this approach, there is the possibility of overfitting the observed data and suppression of some covariates. To account for this, we used bootstrap resampling to identify important patient or procedural characteristics predictive of POD. Third, patients' baseline neurocognitive and functional status were relatively high. POD may predict further cognitive decline only in patients with lower baseline cognitive and functional status. Similarly, although POD did not predict cognitive and functional decline 3 months postoperatively, only 37 patients with POD were available for follow-up testing and the SDs and CIs on the tests were large relative to the mean differences (Table 6). Thus, we cannot exclude a small effect on decline or that decline occurs later than 3 months. Finally, our study does not have adequate statistical power to compare groups using a dichotomous end point (POCD/no POCD). However, based on the distributions of the change scores observed in our study, we are not convinced that a dichotomous end point is the most appropriate way to evaluate changes in cognitive function. Thus, we treated these data in a continuous manner. This approach is consistent with the literature concerning cognitive decline in nonsurgical patients.47
In summary, diminished functional status and lower scores on sensitive neurocognitive tests predict POD in elderly patients undergoing elective total joint arthroplasty. Simple preoperative functional testing may help identify those patients at risk for POD. In this study, POD did not predict cognitive or functional decline at 3 months, suggesting that in this population, POD may not lead to adverse cognitive or functional sequelae and that POD and POCD may be clinically distinct entities. Further study is necessary to more clearly define this relationship.
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APPENDIX: SUPPLEMENTAL ONLINE FIGURE LEGENDS
Figures 1–5 show the distributions of the changes between preoperative and 3-month postoperative neurocognitive test scores for patients with postoperative delirium (POD) and their matched controls. The dashed line represents a 1 SD decline from baseline. In all instances, the distributions are approximately normal and there is no difference in their means. Although for each scale there are some patients who decline by >1 SD, those patients do not appear to be outside the distribution. Given this, and literature suggesting that cognitive decline is best treated as a continuous variable,41 we believe that an analysis comparing the mean change between groups is more appropriate than one that defines postoperative cognitive decline as a dichotomous end point. AVLTLE = Learning Efficiency portion of the Auditory Verbal Learning Test; AVLT%R = Percent Retention portion of the Auditory Verbal Learning Test; AVLTDR = Delayed Recall portion of the Auditory Verbal Learning Test; COWAT = Controlled Word Association Test; SCWT = Stroop Color-Word Test.