Postoperative Delirium and Postoperative Cognitive Dysfunction: Two Sides of the Same Coin?

On the other side of this debate, the “lumpers” can point to at least four key similarities between postoperative delirium and postoperative cognitive dysfunction. First, several risk factors are common to both postoperative delirium and postoperative cognitive dysfunction, such as lower preoperative education level, poor preoperative cognitive function, and depression.⁵  Second, postoperative delirium and postoperative cognitive dysfunction (occurring between 6 and 12 weeks after surgery) are both associated with worse cognitive decline in the 3 to 5 yr after anesthesia and surgery,^4,6,7  decreased quality of life,⁸  and increased 1-yr postoperative mortality risk.⁹  Third, animal studies raise the possibility that common pathophysiologic processes such as neuroinflammation and Alzheimer disease pathology may play a role in both postoperative delirium and cognitive dysfunction.⁵  Fourth, many patients with delirium develop postoperative cognitive deficits, and conversely, many patients with postoperative cognitive dysfunction also had postoperative delirium earlier in their postoperative recovery period (reviewed in Berger et al.⁵ ).

This last point is further strengthened by the findings of Brown et al. in this issue of Anesthesiology.²  They show that in a cohort of 142 cardiac surgery patients, patients with postoperative delirium had significantly worse cognitive function at 1 month after surgery. It is unclear how much of this cognitive decline was really associated with delirium versus lower baseline cognitive function, since the results were not adjusted for baseline cognition. This is a key issue, since it raises the question of whether delirium is simply a marker for other factors that may contribute to postoperative cognitive dysfunction risk, such as lower preoperative cognitive status, versus whether delirium itself actually contributes to longer-term postoperative cognitive dysfunction. Nonetheless, the Brown et al. study²  corroborates previous work by Saczynski et al.⁷ and Inouye et al.,⁶  both of whose studies did adjust for baseline cognitive status and demonstrated that patients with postoperative delirium had worse postoperative cognitive trajectories than patients who didn’t develop postoperative delirium. Interestingly, Brown et al. found no difference in 1-year postoperative cognitive function when comparing patients who did (vs. those who did not) develop postoperative delirium, while other studies have found that patients with postoperative delirium do have worse 1-yr postoperative cognitive function than patients who did not develop postoperative delirium.^6,7  The discrepancy between these findings may reflect the use of different cognitive assessment tools, differing characteristics among these different study cohorts, or simply insufficient power in the Brown et al. study (a type II statistical error). This last point is a reasonable concern, as the studies that have shown 1-yr postoperative cognitive differences between patients with versus those without delirium had approximately 2- to 4-fold larger cohort sizes than the Brown et al.study.^6,7  Despite these limitations, the Brown et al. study demonstrates that patients with postoperative delirium have worsened cognitive function at 1 month after surgery.²  Considering that we have recently argued that postoperative cognitive dysfunction should be conceptualized as a syndrome with a continuous severity distribution,⁵  these data suggest a link between delirium and increased postoperative cognitive dysfunction severity.

So where do we go from here? The debate about the relationship between postoperative delirium and postoperative cognitive dysfunction persists partly because we have an extremely limited pathophysiologic understanding of either disorder. In order to understand the extent of similarity between these disorders and why each is associated with long-term cognitive decline, we need to understand at least three things. First, we need a full understanding of what delirium and postoperative cognitive dysfunction are at a biologic level, ranging from the levels of molecules, to cells, to brain circuits and activity patterns, and ultimately to the dysfunctional neurocognitive processes of each disorder. Second, we need to understand the perioperative factors that contribute to alterations at each of these levels. Third, we need to understand the longer-term trajectory and implications of such pathophysiologic alterations.

Elucidating these pathophysiologic mechanisms of postoperative delirium and cognitive dysfunction is a nontrivial research endeavor that will likely occupy investigators for decades. Yet, there are relatively simple places to start. One potential opportunity is to take a closer look at medical disorders such as obstructive sleep apnea that predispose patients to postoperative delirium and cognitive decline and study what specifically predisposes these patients to these disorders. For example, patients with obstructive sleep apnea have increased levels of systemic inflammatory cytokines, morphologic brain changes, and higher rates of long-term cognitive decline compared to patients without obstructive sleep apnea.¹⁰  Studying specific neuroinflammatory processes in obstructive sleep apnea patients (vs. patients without obstructive sleep apnea) before and after surgery and assessing these patients for delirium and postoperative cognitive dysfunction provides an opportunity to investigate pathophysiologic processes that may play an etiologic role in these disorders. Further, such studies could help lead to future treatments for delirium, postoperative cognitive dysfunction, and even comorbid disorders such as obstructive sleep apnea. And, since anesthesiologists are both airway experts and perioperative physicians, who else is better positioned to understand the links between a disorder that involves the airway (obstructive sleep apnea) and common perioperative complications such as delirium and postoperative cognitive dysfunction?

Regardless of whether obstructive sleep apnea or any other specific comorbid illness contributes to postoperative delirium and cognitive dysfunction risk, the findings of Brown et al. and other studies indicate that postoperative delirium is associated with longer-term postoperative cognitive dysfunction. The key questions for the field now are to understand the mechanism(s) of this association and to clarify the extent to which preventing postoperative delirium also reduces longer-term postoperative cognitive dysfunction.