Photo caption: Dr. Raed Joundi is a Hamilton Health Sciences stroke neurologist whose research focuses on vascular cognitive impairment and dementia.
Alzheimer’s disease, caused by a buildup of abnormal proteins in the brain, has traditionally been the focus of dementia research. But there’s an increasing interest in how vascular issues play a role in dementia, says Hamilton Health Sciences (HHS) stroke neurologist Dr. Raed Joundi, whose research explores vascular cognitive impairment (VCI) and dementia.
The key to unlocking new discoveries lies in large, global, randomized clinical trials focused on vascular cognitive impairment.
VCI is the broad term for thinking and memory problems caused by reduced blood flow to the brain due to stroke, small vessel disease, or other vascular conditions. While this area of study is picking up speed with real progress up ahead, big breakthroughs haven’t happened just yet, says Joundi, a scientist with the Population Health Research Institute (PHRI), the internationally renowned joint research institute of HHS and McMaster University. Joundi was recently named the inaugural Anne Marie Brune/ PHRI Chair in Vascular Dementia. His goal is to push research forward in this field.
Alzheimer’s, VCI, and dementia
Alzheimer’s and VCI are both forms of dementia, but have different causes, symptoms, and brain changes.
While Alzheimer’s is caused by a buildup of abnormal proteins in the brain, VCI is particularly common after a stroke and can cause mild forgetfulness, trouble concentrating or larger challenges with reasoning and decision-making. In many cases, people with VCI can live independently and manage daily tasks while noticing mild cognitive issues, while in others it may lead to a loss of independence.
The most common type of dementia, called mixed, is a combination of Alzheimer’s and VCI, so treating or preventing blood vessel problems in the brain may also slow down the progression of Alzheimer’s disease.
“While treatment of vascular conditions and stroke prevention has improved, there has been a lack of therapies to specifically prevent or treat VCI,” says Joundi. “This will only come with further investigation and discovery. With the pace of research, it’s likely that we’ll discover new, game-changing treatments in the coming years.”
Challenges include a limited ability to build on, or borrow from, past successes in stroke research.
“Treatments proven to be effective for stroke, like aspirin and other medications to lower the formation of blood clots, don’t appear to be as effective in preventing covert stroke,” says Joundi, adding that these are typically smaller strokes which occur without obvious symptoms, but may lead to cognitive decline. “So there are other pathways and mechanisms that we need to explore.”
Charting the Path Ahead
The key to unlocking new discoveries lies in large, global, randomized clinical trials focused on VCI. With randomized trials, participants are randomly assigned to groups, with one group getting the new treatment being tested, and another group receiving standard treatment or a placebo. Randomized trials are considered the gold standard in clinical research.
“Large, global, randomized trials focused on VCI are sorely lacking,” says Joundi, adding that researchers have typically relied on substudies from large trials for other conditions. A substudy is a smaller research project carried out within a larger study or clinical trial.
Joundi is the magnetic resonance imaging (MRI) substudy co-lead for the OCEANIC-STROKE trial, a large international study led by HHS stroke neurologist and researcher Dr. Mike Sharma, a senior scientist with PHRI.
This trial is testing a new anti-thrombotic drug called asundexian, and includes a number of HHS patients. It’s designed to test whether adding asundexian on top of standard treatment can prevent stroke in people who have recently had a stroke or a high-risk transient ischemic attack (warning stroke), without increasing the risk of serious bleeding. The MRI sub-study which Joundi co-leads is looking at whether asundexian can reduce the number of small, hidden strokes in the first six months after a stroke. Since many people develop VCI after having covert strokes, especially if they’ve had more than one, findings could help protect brain function over time.
Joundi also leads the PROSPECT study, an international study focused on understanding what happens to people after they’ve had a stroke. The study follows participants for up to five years, including close to 100 HHS patients so far, collecting detailed information about their cognition, recovery, health, and quality of life over time.
One of the study’s main goals is to understand how stroke affects thinking, memory, and brain function, which are all central to VCI. It’s designed to uncover how and why some people develop VCI after stroke and to test new ways to help prevent or treat it, as well test new treatments. Since it’s a long-term study that follows people over time in many geographic regions, it can be used to support future large, randomized trials.
“All of the information from brain scans and cognitive testing gleaned from previous and current trials and cohort studies — where researchers follow a group of people over time to see how certain factors affect their health — will help lead to a better understanding of the pathways, mechanisms and potential treatments to prevent thinking and memory problems that can happen due to a stroke or vascular causes,” says Joundi, adding, “We’ll build on this work to develop large, global randomized trials focused on VCI.”
Power of Partnerships
Such work, and progress, is only possible due to partnerships in the research community with physicians and with patients.
“The work I’m part of as the Anne Marie Brune/PHRI Chair is really built on the shoulders of those who came before me,” says Joundi. “Without their hard work and discoveries, we wouldn’t be where we are today. And our entire research and medical community is deeply grateful to the patients who volunteer for studies that improve outcomes for people here in Hamilton and around the world.”