Surgery and Cognitive Dysfunction

By Jamie Santa Cruz

Older adults sometimes experience a period of cognitive decline following surgery. But how long might it last—and can it be permanent?

It's been known since 1955 that some patients, particularly older adults, experience a decline in cognition following anesthesia and surgery.1 Since then, the subject of postoperative cognitive dysfunction (POCD) has been controversial, with much disagreement about how the syndrome should be defined, what causes it, and how long it lasts. However, there is little debate today that surgery can prompt transient cognitive impairment in a significant percentage of older surgical patients, and there is concern that the dysfunction may in some cases be permanent.

Definition and Prevalence
In contrast to postoperative delirium, which typically lasts a few hours to a few days after surgery, POCD is generally understood to refer to cognitive dysfunction that lasts from one week up to three months after surgery. It typically involves memory and executive function, according to Roderic Eckenhoff, MD, professor of anesthesia at the Perelman School of Medicine at the University of Pennsylvania; however, there is no established definition and no generally recognized diagnostic criteria.

Because of the lack of definition, estimates vary widely on how many patients experience the disorder. Some researchers have put the incidence of POCD at just 5%, whereas others at the opposite end of the spectrum suggest it is closer to 50%.2,3 But according to Eckenhoff, who is also vice chair of the Brain Health Initiative for the American Society of Anesthesiologists, the bulk of the evidence suggests that between 10% and 30% of elderly surgical patients will experience POCD.

It shouldn't come as a surprise that patients might experience cognitive dysfunction after surgery, says James Rudolph, MD, director of the Center of Innovation in Geriatric Services at Providence VA Medical Center. After all, many facets of the patient experience around an operation interfere with normal brain function.

To begin with, the preoperative experience can be stressful, with patients forced to get up early, fast, and cope with the anxiety of the upcoming operation. The administration of anesthesia and pain medications are explicitly designed to disrupt brain function, and the incision then prompts an inflammatory response on an abnormal scale, which may trigger inflammation in the brain in patients with a weakened blood-brain barrier.

The recovery process poses cognitive difficulties as well. Patients waking up from anesthesia are emerging from a fog, but they may be doing so without the benefit of glasses or hearing aids. Furthermore, the hospital setting typically makes it difficult for recovering patients to sleep, further inhibiting the return to normal cognitive function.

Although younger healthier patients may be able to bounce back easily from these stressors, says Rudolph, the cognitive impact on older adults, especially those who are already in a cognitively impaired state, can be profound.

Can It Be Permanent?
Typically, POCD is a transient disorder lasting up to three months. But there are questions about whether a small subset of patients may experience persistent irreversible cognitive decline.

Suspicions that POCD may in some cases be permanent derive largely from two studies, one of cardiac patients showing decline at five years, and one of noncardiac patients showing decline at one year.4,5 However, both had a relatively permissive definition of POCD, and neither included matched nonsurgical controls. A 2011 review found that in studies where surgical patients are compared to non-surgical controls, there is usually not evidence of persistent POCD.6

More recently, a 2012 prospective cohort study comparing 192 surgical patients to nonsurgical controls has provided evidence that POCD may, in fact, persist beyond up to a year or more in some cases. After tracking participants for 52 weeks, the researchers found evidence of severe POCD in 11.2% of surgical patients compared to only 3.8% of nonsurgical controls.7 In a similar vein, two other large studies with matched controls have found that patients receiving anesthesia and surgery are at higher risk for dementia in subsequent years.8,9

For the present, the subject of persistent cognitive decline remains highly controversial. According to Eckenhoff, however, the contradictory findings with respect to whether or not cognitive change persists beyond three months could be explained by the fact that only certain subgroups of patients are at risk for persistent impairment. "If you include everybody, all comers, the effect is either not there at all or it is very, very small. However, if you focus on certain subgroups [such as patients with a genetic vulnerability toward Alzheimer's Disease (AD) or those carrying the apolipoprotein E4 (APOE4) genotype], these people may have a significant decline."

Mechanisms and Risk Factors
So far, the mechanism by which surgery leads to cognitive decline is unclear. "We're all trying to understand what it is," says Rudolph. "What we're stuck with is a complex model."

When researchers first began to study POCD, the assumption was that it was an anesthetic event: the patient has to "reassemble consciousness" after surgery and might not do it correctly, Eckenhoff explains. More recent research has called this into question, however, and the best indications now point to neuroinflamation as the major player. The belief, Eckenhoff says, is that older patients, particularly those with ongoing comorbidities, have a weakened blood-brain barrier, and the inflammation kicked off by surgery leaks across that barrier, accelerating preexisting inflammation. Since some anesthetics are pro-inflammatory and some are anti-inflammatory, analgesics "could definitely play a role, [but] it's probably a modulatory or minor role," according to Eckenhoff.

Not all patients are equally at risk. Most patients who experience POCD come to the operating table with some kind of preexisting vulnerability, says Thomas Robinson, MD, chief of surgery at the Denver Veterans Administration Medical Center. Mere age represents one form of vulnerability and is the most significant predictor of POCD.10 Preexisting cognitive impairment is another major risk factor, which may suggest that lack of cognitive reserve predisposes patients to POCD.10

Recent research also suggests there may be a gender effect at work. A 2015 study in Alzheimer's and Dementia found that women are at greater risk than men for POCD.11 Although this finding is new with respect to POCD, Eckenhoff notes that it is consistent with the gender effect evident in AD literature, where women are well known to have a greater disposition to cognitive loss.

It is currently unclear exactly how POCD relates to the development of AD; however, there is evidence that patients with underlying AD pathology may be at a higher risk for developing POCD, and anesthesia and surgery may in turn accelerate the AD process.12 According to Eckenhoff, it is possible (though currently not established) that anesthesia and surgery may function as a kind of "stress test" for AD, wherein they reveal signs of AD in patients where the disease was previously unknown.

Practical Guidance for Physicians

• Discuss the cognitive risks with elderly patients who are candidates for surgery.

Particularly if patients are already experiencing cognitive decline, physicians need to discuss with them the potential for further decline. After all, according to Rudolph, many patients fear cognitive impairment more than they fear death. "I suspect a lot of patients are willing to go to surgery and if they die on the table, that's fine, but what they really don't want is to be cognitively impaired and dependent on other people," he says.

This does not necessarily mean physicians should present a picture of gloom and doom. On the contrary, Eckenhoff says, the main message to patients can be one of reassurance. "Tell patients what to expect and that it will probably get better," he says.

• Become familiar with the patient's cognitive function before surgery.

The USPSTF recommends against routine cognitive screening. That said, since preoperative cognitive impairment is an important risk factor for POCD, Rudolph maintains that physicians should get a sense of a patient's cognitive function prior to surgery. "Recognize that those patients who are more cognitively impaired may have a tougher time with surgery," he says.

• Do neuroprotective operations and give less anesthesia.

For example, says Robinson, perform a smaller operation where possible rather than opting for a more extensive one. Likewise, give less anesthesia, such as by administering a regional anesthetic block and administering less of the inhalation agent. There is some evidence, he notes, that titrating anesthesia using a bispectral index (BIS) monitor and avoiding deep sedation may lower the risk of POCD.7,13

• Minimize the stress of surgery from a psychological perspective.

Since preoperative stress may induce cognitive changes in patients even before surgery, physicians should do as much as possible to reduce anticipatory anxiety, Rudolph says. Clinicians should also ensure patients are getting cognitive stimulation postoperatively through various senses to help them become oriented as quickly as possible.

• Engage in longer-term follow up.

In many cases, Eckenhoff says, physicians—especially anesthesiologists—may not know that their patients are experiencing cognitive loss after an operation because their patients simply don't tell them. Therefore, clinicians should take the initiative to follow up, not just in the short term but over the longer term as well.

For a long time, according to Robinson, clinicians working in and around the operating room have been slow to acknowledge the existence of POCD. That situation has been changing, he says, with more anesthesiologists and surgeons becoming attuned to the issue, but the surgical team needs to continue to proactively incorporate what is known about POCD into the care pathway. "Now that we're aware that cognitive dysfunction is a major issue for older adults, we need to actively start addressing it."

— Jamie Santa Cruz is a freelance writer based in Englewood, Colorado.

References

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2. McDonagh DL, Mathew JP, White WD, et al . Cognitive function after major noncardiac surgery, apolipoprotein E4 genotype, and biomarkers of brain injury. Anesthesiology. 2010;112:852-859.

3. Abildstrom H, Rasmussen LS, Rentowl P, et al. Cognitive dysfunction 1–2 years after non-cardiac surgery in the elderly. ISPOCD group. International Study of Post-Operative Cognitive Dysfunction. Acta Anaesthesiol Scand. 2000;44:1246-1251.

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13. Chan MT, Cheng BC, Lee TM, Gin T; CODA Trial Group. BIS-guided anesthesia decreases postoperative delirium and cognitive decline. J Neurosurg Anesthesiol. 2013;25(1):33-42.