12 minute read
The Alzheimer’s study
A new pathway for preventing dementia?
Craig Weinkauf, MD, is leading a trial looking into a connection between carotid stenosis. ‘We want to try to quantify the brain: volumes, structural connectivity, functional connectivity and other relevant findings associated with neurodegeneration,’ he tells Beth Bales
Society for Vascular Surgery (SVS) member Craig Weinkauf, MD, enrolled patient No. 1 just a few months ago in a National Institutes of Health (NIH) study to determine the impact of carotid disease on cognitive impairment and Alzheimer’s disease.
Alzheimer’s affects an estimated 5.8 million Americans and is the fifth-leading cause of death among those 65 and older. It is the most common type of dementia.
Carotid disease can be slowed or reduced though lifestyle management, medication and surgical intervention. Because it’s modifiable, finding a connection between carotid disease and Alzheimer’s could provide a new pathway for decreasing dementia risk, Weinkauf said..
He is leading the study, funded by a $4.9 million NIH grant, working with a host of other experts in neuroimaging, magnetic resonance imaging, vascular disease, Alzheimer’s disease and neurocognitive function. Weinkauf is an assistant professor in the Department of Surgery’s division of vascular and endovascular surgery at the University of Arizona College of Medicine.
Carotid disease, in which vessels carrying blood to the brain become occluded, causes 10 to 20% of strokes. Weinkauf said that many physicians might not consider it a major problem if one or two of these blood-carrying vessels are occluded because the brain still has so much collateral blood flow. The point of the study, he said, is what if this thinking is wrong?
“We’re looking into this question: does carotid disease infer specific risk for Alzheimer’s disease beyond that of baseline cardiovascular-risk factors?” Weinkauf said. “We’re looking beyond stroke, beyond general cardiovascular risk factors, at how blockages in the arteries that lead to your brain affect your brain health?”
Researchers started in March and will continue over the next five years to recruit roughly 240 patients, primarily in Arizona. Then, with advanced imaging, neurocognitive testing, and other specialized tests the researchers will investigate which specific pathological changes specific to Alzheimer’s are associated with carotid disease; how (and if) carotid disease leads to those changes; and which treatments for carotid disease are effective at preventing or improving Alzheimer’s-associated neurodegeneration.
The team will start by determining patients’ baseline cognitive function, and what constitutes a normal decline that comes with aging.
This trial continues research from an earlier project in which Weinkauf and close collaborators tried to see if they could quantify cognitive function and changes in the brain. They quantified various aspects of cognition and brain structure, including brain volumes of the Hippocampus, the portion of the brain that supports memory—especially new memories, learning, navigation and space perception. It is also thought to perhaps play a role in Alzheimer’s disease.
The brains in Alzheimer’s patients have a “quantifiably smaller” Hippocampus, said Weinkauf. “We found the same thing in patients with severe carotid stenosis (defined as >70% stenosis) compared to well matched controls with <50% carotid stenosis bilaterally.
“It’s something you can quantify to see if something’s changing. The project started by asking these kinds of questions.
“We want to try to quantify the brain: volumes, structural connectivity, functional connectivity and other relevant findings associated with neurodegeneration,” he continued. “We didn’t have these tools 20 years ago, or even five years ago in some cases, so even if someone had thought of this then they wouldn’t have necessarily had the tools to investigate.
“We’re lucky to have surgical treatments for this problem,” he said. “We will also be able to follow that population to see if they have key structural and functional brain changes that improve with intervention.” Related questions are being asked in various ways by other groups as well, including the CREST-H (hemodynamics) part of the CREST-2 trial. “It is clear that these types of questions are in the air and hopefully as a field we will be able to improve care for our vascular patients by better understanding the connection between carotid artery stenosis and brain health.”
Some carotid patients have told him that, following a procedure for carotid disease, their vision, hearing and thinking all improved, he said. “I think there’s more overlap between these two large patient populations, those with carotid and those at risk for Alzheimer’s than is currently appreciated.
The research team hopes to be able to determine if baseline factors can identify those people at increased risk for Alzheimer’s and/or other forms of cognitive impairment and dementia. In a similar fashion they will be looking to determine which baseline factors may help define who benefits from intervention. “This strategy gets at a key deficit in how we currently approach carotid disease management: there is minimal patient selection for defining subpopulations of patients with carotid disease who may benefit most from treatment,” Weinkauf added. “Risk-stratification of this population will be integral for honing/improving our vascular care and obtaining important objectives like personalization of carotid vascular care. We hope that our study can help us better understand brain health in our patients and define key, quantifiable markers that help guide our surgical care.”
CRAIG WEINKAUF
For more information or to learn about enrolling patients contact Weinkauf at cweinkauf@surgery.arizona.edu.
PUBLIC AWARENESS SVS HAS PATIENT RESOURCES AND GUIDELINES ON STROKES
May was Stroke Awareness Month, and the Society for Vascular Surgery (SVS) and SVS Foundation offer educational resources for Society members to provide as a resource to their patients at risk of the potentially devastating disease no matter the time of year, writes Beth Bales
THE SOCIETY ALSO HAS CREATED
clinical practice guidelines that evaluate the evidence in the scientific literature, assess the likely benefits and harms of a particular treatment, and enable healthcare providers to select the best care for a unique patient based on his or her preferences. SVS guidelines aid members and their patients in the decision-making process. Visit vascular.org/CPG to see the guidelines.
Patient resources include detailed information about strokes, including symptoms, causes, diagnosis, treatments and prevention. In addition, SVS offers patient fliers on carotid artery disease, cholesterol, smoking and physical activity, all of which impact vascular health and disease.
As members know all too well, smoking is a major cause of strokes and cardiovascular disease leading to strokes. Physical activity, likewise, helps prevent strokes and other vascular conditions and illness.
Members can download patient education fliers from the patient-education portion of the SVS website at vascular.org, or via the members-only Branding Toolkit; those materials can be customized with a member’s name, practice and contact information. Any of the materials can then be available in members’ offices or mailed or emailed to at-risk patients.
“We all know the numbers,” said SVS President Ali AbuRahma, MD. “We know that up to 5% of people older than 65 have carotid artery disease, which increases the risk of stroke, that cholesterol is a top factor when it comes to vascular disease, and that lifestyle changes such as quitting smoking and increasing physical activity are major preventive measures.
“Help your patients by helping educate them,” he said. “You never know what piece of information might make the difference and turn things around.”
The Branding Toolkit also includes condition fliers, including one on claudication, that can be customized and sent to referring conditions.
Artificial intelligence could make endovascular aortic repair outcomes more predictable, CX 2022 hears
By Jocelyn Hudson
AT THE 2022 CHARING CROSS (CX) INTERNATIONAL
Symposium (April 26–28) in London, England, Tom Carrell, MD, a vascular surgeon in Cambridge, England, and founder of Cydar Medical, delivered a Podium 1st presentation titled “Making endovascular aortic repair outcomes more predictable: Artificial intelligence [AI] takes on a 20-yearold challenge.”
“Given any individual patient with some anatomic complexity, do we really know—particularly with the ever-expanding range of treatment options— what is going to be the outcome for them?”
According to Carrell, this is the key question at the center of the 20-year-old challenge the speaker referred to in the title of his talk. Twenty years ago, he detailed, the pioneers of endovascular surgery recognized that anatomic severity was a major determinant of outcomes and therefore probably required reporting standards. “A scoring system would need to strike a balance between having enough granular detail to be useful and also being simple enough to be usable in everyday practice,” he said. A scoring system was built, with the expectation being that subsequent clinical investigations to test the system would be used to modify it.
In the 20 years since then, Carrell highlighted that a number of papers on the anatomic severity grade scoring system have been published, showing that it does indeed predict outcomes and complications. However, “there has not been quite so much progress in terms of using that data to modify the schemes,” Carrell pointed out.
The speaker noted that there are probably a number of reasons for this, one being that “some of the things that go into the scoring schemes turn out to be rather complicated.” For example, he said, measuring infrarenal neck angulation is “really contentious,” with “very high intraobserver variability.”
“Can AI offer both that detail and simplicity?” Carrell asked, highlighting a key question in 2022. He explained that Cydar Medical is developing an extended capability to operate with what the company calls Intelligent Maps. “The concept is that when you plan a case, you are being informed by the outcomes of previous patients with similar anatomy and disease,” he explained.
The company’s current product, which is used for planning, guiding, and reviewing endovascular surgery, uses “virtual guidewires.” Carrell elaborated: “We use [virtual guidewires] for planning, but the main function is to identify where you are going to be operating, so that your planning is rendered in the form of a map and overlaid on a live fluoroscopy. As your real guidewires deform the anatomy, the virtual guidewires deform the map so that you have an overlay that reflects the real-time anatomy.”
Carrell provided some details on where the software is headed: “What we are doing with Intelligent Maps is taking that capability with the virtual guidewires and the AI that we have in the system and the data from all the thousands of patients who have been treated with Cydar EV Maps and building tools to analyze anatomy.” He added that these tools are a combination of deterministic algorithms using the virtual wires and also using simulated neural networks, or deep learning, to not just segment the vessels, but also to label the aorta and the iliacs according to what branches are coming off at each level.
“For each patient, you bring these things together so that you have your geometry, but you have it in the context of where you are right the way along the aorta and the iliac system. This is highly deterministic, so you put the CT [computed tomography] scan in and these measures come out, put the same CT scan in or a similar CT scan in and you get the same things coming out.”
One of Carrell’s key takeaway messages was that this software has relevance for helping inform decision-making. “You take one patient that produces the analytics and then we use it to match to other patients in the database already, patients who have similar anatomy. It is literally as simple as entering in the CT scan and finding those matching patients. We can then find out what treatment those patients had, what type of approach they had.” Next, Cydar will be working on bringing in the “final steps” of the technology—the outcome metrics for the surgical strategy that was used. “We want to close that 20-year ambition to have the feedback loop in there to modify the scoring system,” Carrell concluded.
for them?” TOM CARRELL
COMPLEX REPAIR
Cloud-based fusion imaging found to improve operative metrics during FEVAR
Asingle-center retrospective review demonstrated a trend towards shorter operative times, and significant reductions in both iodinated contrast use and radiation exposure during fenestrated endovascular aneurysm repair (FEVAR) using Cydar’s EV Intelligent Maps—representing the first report of an improvement in metrics with the Zenith Fenestrated (ZFEN) graft while utilizing the fusion imaging system, according to the study authors. “Intelligent map guidance improves the efficiency of complex endovascular aneurysm repair, providing a safer intervention for both patient and practitioner,” concluded Charles J. Bailey, MD, and colleagues from the University of South Florida and Tampa General Hospital.
Results from the study were presented during the 2022 annual meeting of the Southern Association for Vascular Surgery (SAVS) held in Manalapan (Jan. 19–22).
A retrospective review of a prospectively maintained aortic database was performed to identify all patients who underwent commercially available FEVAR between 2013 and 2020, as well as all endovascular aneurysm repairs performed using Cydar’s cloud-based fusion imaging platform at the institution starting from 2018.
Being solely focused on de novo FEVARs, a comparative analysis was performed on 53 FEVAR procedures carried out without, and 63 with, EV Intelligent Maps. Cohorts were found to be similar in terms of patient demographics, medical comorbidities and aortic aneurysm characteristics. Bailey highlighted that body mass index was the same across both cohorts—”something to consider, as the larger the patient, the more radiation they will require.”
No significant difference in major adverse postoperative events, length of stay, or length of intensive care unit stay was detected between the groups, the research team noted. Use of EV Intelligent Maps resulted in non-significant decreases in mean fluoroscopy time (69.3 vs. 66.2 minutes, p=0.598), and a positive trend towards shorter operative times (204.4 vs. 186 minutes, p=0.278). Notably, a statistically significant decrease in both iodinated contrast volume (104.7 vs. 83.8ml, p=0.005), and patient radiation exposure via dose-area product (1049841 vs. 630990mGy/cm2, p<0.001) was observed in patients undergoing FEVAR with Cydar EV Intelligent Maps, the researchers reported.
Furthermore, Bailey noted the learning-curve element involved in use of the imaging platform, describing how the team took the relevant 63 patients and divided them into groups of 10. “After the 10th case, there was a significant and sustained reduction in radiation exposure,” he said.
Baily told SAVS 2022: “This is a single center retrospective review. There is a learning curve to any novel technology. Maybe there is a bias to how much attention we pay to distance from operator … practitioner to radiation source, but it’s what we have embraced to do these complex procedures safely, both to us and the patient and practitioners in the room. This is where we should be thinking with complex endovascular devices.”—Bryan Kay
