“…we’re still looking into the black box when we look at the brain.”
By Sandra Gordon for ASA
In this Q&A, Nicolai Goettel, MD, Senior Consultant in Anesthesiology at the University Hospital Basel and Research Group Leader at the University of Basel, Switzerland, discusses his research with postoperative cognitive decline and structural MRI.
Q: Dr. Goettel, can you tell us about you and your background?
As a clinician-scientist at the University of Basel, I’ve been doing cognitive outcomes research for the past seven years, focusing on postoperative delirium (POD) and postoperative cognitive dysfunction (POCD), which are now known as perioperative neurocognitive disorders (PNDs) under a new nomenclature.
The occurrence of PNDs has a huge economic impact and leads to patient-related adverse outcomes such as loss of independence and increased mortality. Even though we have a new definition and speak a common scientific language, it’s often difficult to compare studies due to substantial differences in methodology. Ideally, there should be a more cooperative and straight-forward approach to this type of research. Most research investigations that deal with POD and POCD are hypothesis-generating. I think some of it is based on the fact we’re still looking into the black box when we look at the brain.
In any event, I chose neuroanesthesiology as my profession and neurocognitive outcomes of surgery and anesthesia as my research field, because I’m convinced that the most interesting scientific endeavors and discoveries in the years to come are going to be related to the human brain. I simply wanted to be part of that journey.
Q: Can you tell us about your recent research with POCD and structural MRI?
At the University of Basel, we looked at 70 patients over the age of 65 years undergoing major, noncardiac surgery. We administered an extensive preoperative neurocognitive assessment, as well as structural MRI to those patients before, and three months, and one year after surgery. We are fortunate to have an exceptional collaboration with the University of Basel’s geriatric hospital affiliated Memory Clinic, which is one of the most prolific memory clinics in Switzerland. For this study, we applied neuropsychological test batteries used in the diagnosis of Alzheimer’s disease to our needs, testing patients in multiple cognitive domains, such as verbal and visual memory, language, and executive function.
Patients underwent surgery under a standardized anesthesia protocol. Then, we performed longitudinal neurocognitive testing and MRI. We included a group of non-surgical controls, matched to age, sex, and education, to take into account the natural rate of cerebral atrophy in healthy adults. Every year of life, the cerebral volume, the total brain mass, decreases by about 0.1% to 0.3%, starting at a relatively young age, and accelerating with increasing age. It’s just a part of the normal aging process. The question is: Is that brain atrophy faster or more pronounced in patients who undergo surgery somewhere along the line, or not?
Q: Can you reveal the results of your study?
We haven’t finishing analyzing the results, but I had a sneak peek. The results aren’t as promising as we thought, which reflects the literature. Other studies are very heterogenous and sometimes even contradicting when it comes to anatomical biomarkers of POCD.
Keep in mind that doing those studies is extremely complex, difficult and expensive, especially when POCD is the aim. You always need a pre- and a postoperative neuropsychological test to compare, and the timing needs to be right. On top of that, with POCD, the cognitive changes are sometimes very subtle. Other large longitudinal cohort studies, such as the SAGES, BioCog, INTUIT, and TORIE projects, are on the way and may shed some light on the cerebral imaging correlates of PNDs. Perioperative cognitive outcomes research based on MRI is increasingly popular.
Q: What lessons can we learn about postoperative delirium from Alzheimer’s disease and brain imaging research?
The idea that surgery or anesthesia could have an impact on the brain’s anatomical and functional structure comes from Alzheimer’s disease research. To be honest, they’re way ahead of us in brain imaging, be it conventional or functional.
In Alzheimer’s disease, you can see structural brain changes, especially in specific brain regions such as the hippocampus, the entorhinal cortex, and the amygdala, years before the onset of clinical symptoms.
So far, there is no solid evidence that structural MRI changes are associated with either POD or POCD. What seems to be more relevant, especially when it comes to delirium, are the neurovascular changes, such as white matter hyperintensities and cerebral infarcts that you may identify on MRI.
If neurovascular changes prove to be a surrogate biomarker for cognitive changes after surgery, we could do an MRI in every elderly patient scheduled for major surgery. If the correlation between the predictor and the outcome is high, it’s probably worthwhile doing this MRI because we could then target high-risk patients with preventive interventions, or nurture a discussion with the patient about treatment goals.
For some, especially very old patients, it could be helpful to have this kind of information because they may end up with a great surgical result, but with delirium or memory loss. That’s something you have to weigh. This is where I see a place for biomarkers that may help to anticipate adverse cognitive outcomes. You can only make an informed decision about whether or not to have surgery if you see the full picture.
Q: What do you do to assess a patient’s cognitive function before surgery at your clinic?
It is important to assess cognition in older patients before surgery, and to do so in a routine fashion. We have developed our own self-administered and completely language-free perioperative cognitive assessment tool, called CogCheck, which works as an application on an iPad. You can just hand it to patients during the preoperative evaluation, and they do a series of cognitive tests by themselves. The whole thing takes about 20 minutes. At the end, you have an estimation of the individual cognitive performance of your patient. We’re currently validating the tool in patients undergoing cardiac surgery to find out if we can actually predict POD.
Q: Is the CogCheck tool widely available?
We created the CogCheck application in 2015 and have gradually refined it through extensive clinical research. It’s not commercially available, but that’s not our goal. We want to promote it as a research tool and give it away freely to every researcher and clinician who is interested.
Q: In the meantime, it sounds like the brain will continue to be a black box for the foreseeable future.
Yes, right now, advanced imaging and PNDs offers more questions than answers. But cognitive changes after surgery and anesthesia is a subject that’s increasingly important because people are getting older, and more older patients undergo surgery. The “silver tsunami” has also arrived in Switzerland. For men, we now have the highest average life expectancy in the world, approaching 83 years. As a consequence, unless you’re doing obstetric or pediatric anesthesia exclusively, you’re already a geriatric anesthesiologist. Taking care of elderly patients will be a big part of our professional life.
Current MRI technology is performing better than ever before. In the future, it will get cheaper and more accessible. In Basel, a small city of just 200,000 inhabitants, we had some 15 MRI scanners in 2019. They need to turn. We will see more patients undergoing these imaging studies before surgery, and new insights into the pathophysiology of PNDs will emerge from advanced cerebral imaging. We’re slowly poking small holes into the black box to look into the brain and see what’s going on there. It’s a long but fascinating process, I can promise you that.
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