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Published on: November 12, 2018
by Women’s Brain Health Initiative:
The administration of general anesthesia (an anesthetic used to induce unconsciousness during surgery), and its potential for long-term cognitive effects, has been under intense scrutiny. Memory loss after surgery affects more than 35% of young adults and 40% of elderly patients at the time of hospital discharge.
THREE MONTHS AFTER SURGERY, APPROXIMATELY 6% OF YOUNG ADULTS AND 13% OF ELDERLY PATIENTS CONTINUE TO SUFFER FROM MEMORY DEFICITS AND OTHER FORMS OF COGNITIVE IMPAIRMENT – the kind that interfere with the ability to remember names, locate a car in a parking lot, or find a set of keys.
As early as 1955, in one of the first publications to connect anesthesia with cognitive impairment amongst elderly patients, Dr. P.D. Bedford observed that in some cases, “minor dementias and even permanent catastrophic mental impairment may occasionally be the aftermath” of having received a general anesthetic. Since then, researchers have been investigating the relationship between general anesthesia and dementia but have generated inconsistent results.
Research published in the Journal of Clinical Investigation in 2014 sought to examine what exactly occurs in the post-operative brain. “One of our fundamental assumptions has always been that once the [anesthetic] drugs were eliminated, the brain goes back to the baseline state,” says Dr. Beverley Orser, co-author of the study and Chair of the Department of Anesthesia, as well as a Professor of Anesthesia and Physiology at the University of Toronto. But what Dr. Orser and her colleagues found was that in addition to the “desired, profound anesthetic action, which is due to the drugs interacting directly with the receptors” – which is necessary for the surgery itself – “the memory blocking receptors were hanging around and causing subtle impairment” in animal models after the drugs were eliminated. Specifically, they found issues with memory and problem solving in the mice, she says. Human trials are currently being organized to explore this occurrence further.
According to research published in the journal Current Opinion in Critical Care in 2011, postoperative confusion and cognitive problems are more common in elderly patients (over 65 years old) than younger patients, and can be categorized as postoperative delirium, postoperative cognitive dysfunction (POCD), and dementia. The presentation of postoperative delirium is variable and patients may exhibit hyperactivity, hypoactivity or mixed hyper-hypoactivity.
Hyperactive patients show increased psychomotor activity, such as rapid speech, irritability, and restlessness, whereas hypoactive patients show a calm appearance combined with inattention, decreased mobility, and have difficulty answering simple questions about orientation. POCD, on the other hand, is harder to define since it “is a subtle impairment of memory, concentration, and information processing that is distinct from delirium and dementia.”
The symptoms of POCD vary from mild memory loss to an inability to concentrate or process information. “POCD and dementia appear clinically similar,” says Dr. Juraj Sprung, an anesthesiologist and professor of anesthesiology at the Mayo Clinic in Rochester, Minnesota, who has published work on this topic in Mayo Clinic Proceedings and has new research findings currently undergoing review at the British Journal of Anaesthesia, “the only real difference is that POCD is believed to be transient.” Interestingly enough, even though it has been well established that women are at a higher risk for developing Alzheimer’s disease, “there is no gender bias at all to any of the perioperative disorders, as far as we know,” says Dr. Roderic Eckenhoff, an anesthesiologist at The University of Pennsylvania.
Both postoperative delirium and POCD are “considered to be reversible processes,” says Dr. Sprung. The length of recovery from postoperative delirium or POCD varies between weeks or months, depending on the individual. However, suffering from post-
operative cognitive deficits for any length of time should not “be undervalued,” says Dr. Orser. “If we’re looking at months, those are really important decision-making times,” she says. For instance, you might be deciding whether your parent should go back home after surgery, or whether he or she should move to a long-term care facility. “So while it’s short-term, it’s a very critical part of one’s life around the time of surgery.”
CAN YOU DEVELOP DEMENTIA FROM ANESTHESIA?
Researchers are currently investigating whether lasting cognitive impairment can result from the administration of general anesthesia. “In animal models, there does seem to be a bit of a signal that anesthetics alone can enhance the pathology of some of the neurocognitive diseases,” says Dr. Eckenhoff. In humans, “we’ve known for a long time that there is a cognitive hit from having surgery and anesthesia. But the real controversy at this point is how long it lasts and does it lead to accelerated permanent neurodegeneration. That’s the real crux of the question right now, the controversy: Does it lead to long-term decline?”
To date, the results of clinical studies with human subjects have suggested that there is “no association between anesthesia and long-term mild cognitive impairment (MCI) or dementia,” says Dr. Eckenhoff. Dr. Sprung agrees: It is clear from most of the recently published literature that you do not develop dementia from anesthesia. Dr. Sprung and his team have found that
THERE IS NO SIGNIFICANT ASSOCIATION BETWEEN EXPOSURES TO PROCEDURES REQUIRING GENERAL ANESTHESIA AFTER THE AGE OF 45 AND INCIDENT DEMENTIA.
For those individuals who do not recover their cognitive abilities after surgery, there are a few explanations for this occurrence, according to Dr. Sprung. Surgery itself is stressful on the body – the body releases steroids and inflammatory cytokines during surgery, which can accelerate the death of brain cells, and dehydration can play a role too, all of which factor into the burden of disease, says Dr. Sprung. In essence, “the sicker you are, there is a greater chance that you will progress towards the state of dementia over time.”
It is also a well-established fact that a patient’s comorbidities (when an individual has two chronic diseases at the same time) and associated hospitalizations pose a risk for the progression of cognitive impairment in the elderly. In other words, “if you come in with a vulnerability to surgery – let’s say you already have MCI, or you have long-term diabetes, or vascular disease, or even sleep apnea – that puts you at increased risk of having cognitive decline caused by both the surgery and the anesthesia,” says Dr. Eckenhoff. An individual who is older (and most likely sicker), and who has preexisting conditions, may fare worse after surgery and anesthesia than a relatively healthier younger person, because the older person’s burden of disease is likely higher.
But many researchers believe that the anesthesia is a “pretty minor player,” says Dr. Eckenhoff. They believe that it is the neuroinflammation caused by surgery that actually plays a predominant role, but more research needs to be conducted. The brain is “usually protected from inflammatory assaults with a good blood-brain barrier,” explains Dr. Eckenhoff, but as we age, that barrier begins to deteriorate and “peripheral inflammatory responses can get into your brain more easily.” The ensuing inflammation caused by hip surgery, for instance, can also cause inflammation in the brain.
Other studies have suggested that the type of anesthetic that is used may play a role in how the surgery affects cognition. “Propofol, for example, appears to be a little anti-inflammatory and we do think that this has a bearing on the degree of neuro-inflammation and any cognitive decline afterwards. But even having said that, we think the anesthesia plays a small factor,” says Dr. Eckenhoff.
Dr. Sprung and his team have hypothesized that individuals who do develop cognitive decline or dementia after surgery were already on the precipice of developing dementia in any event.
UNDERGOING SURGERY MAY BE COMPARED TO A ‘STRESS TEST’ THAT UNMASKS UNDERLYING COGNITIVE DEFICIT, says Dr. Sprung. In other words, surgery and anesthesia “can uncover individuals who are on the trajectory to develop cognitive impairment anyway, either mild cognitive impairment (MCI) or pre-dementia, or even dementia.” For those who were already on the verge of developing dementia, then, the process can be accelerated by surgery.
It is important to remember, though, that dementia and Alzheimer’s disease develop over several years, as opposed to overnight. When an individual is already sick, he says, there is a higher chance that he or she will need surgical procedures and receive a general anesthetic (and then anesthesia incorrectly gets blamed for the cognitive decline). Dr. Sprung and his team examined over 1,700 individuals – approximately half with dementia and half without – and they did not find any direct association between anesthesia and dementia.
Nevertheless, Dr. Sprung still worries when he is administering anesthesia to an older patient. He understands that older patients, particularly those who already suffer from MCI, have “an increased likelihood to fare worse after surgery.” If the recovery from cognitive impairment takes longer, or if the individual dies from an unrelated disease in the interim, relatives and medical professionals may misattribute this cognitive deficit to anesthetic exposure, says Dr. Sprung.
Furthermore, researchers have found that individuals who have MCI have a greater propensity of developing postoperative delirium, which has been linked to accelerating the onset of cognitive decline – even in those who test as cognitively normal prior to undergoing surgery. Dr. Sprung believes that postoperative delirium can either accelerate the onset of dementia or, alternatively, those who were testing as cognitively normal may have actually been on the border of normality or on a declining trajectory towards MCI before surgery.
WEIGHING THE SCALE
What do you do, then, when you or a loved one requires surgery but is hesitant to receive general anesthesia?
DON’T CANCEL SURGERY THAT YOU NEED BECAUSE OF THIS, says Dr. Orser, but “do be mindful of it. Be reassured that we’re trying to work hard to identify the extent of this problem and the correctable factors, and meanwhile there’s an evolving literature that patients can turn to, to think about what supports they need.”
For instance, individuals can visit the Perioperative Brain Health Centre located at Sunnybrook Hospital. Dr. Eckenhoff says that there are quite a few things that individuals can do to prepare for a surgery. The American Society of Anesthesiologists has a new website through its Perioperative Brain Health Initiative (asahq.org/brainhealthinitiative), which is meant to help patients over the age of 65 with cognitive recovery after surgery. Individuals can also engage in “pre-
habilitation,” which means “remaining active and exercising right up to the point of surgery,” says Dr. Eckenhoff. It is also important to speak with your anesthesiologist before your surgery, as there are things that he or she can do interoperatively in order to reduce the risk of delirium after surgery (such as monitoring blood pressure and using brain vascular monitors to observe how the brain is being oxygenated throughout the procedure).
Dr. Eckenhoff also suggests minimizing the use of certain medications (subject, of course, to your doctor’s approval). For instance, elderly individuals “don’t tolerate benzodiazepines particularly well,” so it is useful to avoid those before, during, and after surgery if possible. After surgery, also ensure that you get your eyeglasses and hearing aids back quickly to orient yourself, if applicable (talk to your doctor or family member beforehand to ensure that this happens) and get sleep, as it is critical for your recovery. Finally, be your own advocate (or be an advocate for a loved one) – it is important to ask questions in order to be as prepared as possible for surgery.
Source: MIND OVER MATTER V7
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