Drug discovery and domestic violence risk factors in dementia
December 4, 2019
The most effective way to address dementia is to tackle it from many different angles. And that’s precisely what the Director and Senior Scientist at the Krembil Research Institute at the University Health Network, Dr. Donald Weaver, does through both his basic science and clinical work.
Dr. Weaver’s basic science research is focused on designing and developing new drugs that will slow or stop dementia. Along with his 40-person research team of synthetic chemists, computational chemists and biologists, Dr. Weaver uses computers to model potential dementia drugs that can enter the brain, bind to toxic proteins, and prevent them from further clumping. Once designed, his team then develops the drugs and performs pre-clinical tests to ensure the drugs function as predicted.
Dr. Weaver and his team are focused on designing drugs that will modify the disease course of dementia. This includes targeting two proteins - β-amyloid and tau - that fold incorrectly and form clumps in the brains of people with Alzheimer's disease, which then block communication between brain cells and eventually kills these cells. Another target is the immune cells in the brain that contribute to increased inflammation in dementia.
“Looking for potential drugs to treat dementia is a much needed area of research,” Dr. Weaver points out, “We have drugs on the market for dementia but they are symptomatic not curative treatments, therefore they are of limited value. The goal is to create a disease-modifying drug that stops dementia in its tracks.”
In addition to his basic science research, Dr. Weaver also has an ongoing clinical project looking at domestic violence as a risk factor for dementia. Sparked by a patient encounter, Dr. Weaver began researching the link by asking patients with dementia in his clinical practice about domestic violence.
“Domestic violence affects 17% of relationships,” Dr. Weaver says, “People who have experienced domestic violence may go on to develop dementia pugilistica, which is similar to what boxers may experience. It’s an issue that needs to be understood and addressed better.”
Bringing together his training in medicine, organic chemistry and quantum mechanics, Dr. Weaver hopes to attack dementia from different angles – by not only looking for new drugs that can treat dementia but also understanding some of the clinical risk factors.
Although Dr. Weaver acknowledges some big challenges facing dementia researchers, such as the lack of blood tests to diagnose dementia and the lack of disease-modifying drugs currently on the market, he is hopeful about the future of dementia research and the impact that families can have in the fight against dementia: “The most important thing is to not give up hope. Despite the challenges, there is room for hope and optimism. It is important to have people with dementia and their care partners support research and if possible, participate in research studies to help us uncover new discoveries and new treatments.”
To learn more about Dr. Weaver’s research, visit: https://www.uhnresearch.ca/researcher/donald-f-weaver.
Let’s talk about the D word – dementia. What is dementia?
Dementia is the umbrella term used to describe decline in mental abilities severe enough to interfere with daily life. Dementia describes a group of symptoms including loss of memory, impaired communication, judgement and reasoning abilities among other cognitive issues. Often times these symptoms are confused with normal aging, and while it may be true that as we age our mind may not be as sharp – dementia is not a normal part of aging.
What causes dementia?
Dementia is caused by damage to brain cells. This damage affects the ability of brain cells to communicate with each other. Many diseases can cause dementia and these conditions can have similar and overlapping symptoms.
But why does dementia occur in some cases and not others?
The short answer – we’re just not sure, it’s rather complicated with multiple contributing factors from genetics to lifestyle choices. Dr. Mario Masellis, scientist and neurologist at Sunnybrook Health Sciences Centre, explains that “if you’re diagnosed with dementia over the age of 65, you’re more likely to have more than one pathology contributing to it.” The challenge is understanding the underlying mechanisms of dementia.
“Currently, the identification and development of biomarkers for dementia is in its infancy” says Dr. Masellis. Biomarkers (or biological markers) are measurable indicators that can help clinicians predict, diagnose or monitor disease. Drawing from his background in pharmacology, Dr. Masellis’ research examines the complex interplay between pharmacology, genetics, brain imaging and neurodegenerative diseases to better understand the contributors to cognitive decline.
“We need to work with the community to learn more about the pre-symptomatic stages of dementia” says Dr. Masellis, who also leads the Ontario Neurodegenerative Disease Research Initiative (ONDRI). ONDRI is a provincial research program in partnership with the Ontario Brain Institute designed to investigate the similarities and differences among dementia, particularly in the following:
- Alzheimer’s disease/mild cognitive impairment,
- Parkinson’s disease,
- Amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease),
- Frontotemporal lobar degeneration, and
- Vascular cognitive impairment (resulting from stroke).
Instead of only studying what’s unique to each disease, ONDRI’s long-term observational study is seeking out the common early indicators and risk factors of the five diseases. With over 520 participants enrolled in ONDRI, researchers can study each cohort in the same way by collecting standardized data from: MRIs, cognitive testing, optical coherence tomography (eye testing), gate & balance, and genetic testing.
But this is really just the beginning! The next phase of ONDRI is to collect data from home – participants will use wearable devices for a week and researchers will compare the results against the standardized data. Dr. Masellis and the ONDRI team are also looking to expand and combine approaches with international databases in order to better understand neurodegenerative diseases.
If you’re interested in learning more on ONDRI please visit http://ondri.ca/ or contact:
416-480-6100 ext. 6661
Dr. Michelle Greiver – a family doctor for over 30 years – is at the frontier in revolutionizing knowledge translation in the healthcare system. “As a practicing physician, I am dedicated to people and am passionate about providing quality care,” says Dr. Greiver, who does not see her patients as patients but as people.
“I became very frustrated with the current healthcare system due to the lack of knowledge translation available”. To better serve the community, “improved communications and systems must be put in place for clinicians to better access information and deliver quality care”, said Dr. Greiver.
This is the mandate of the University of Toronto Practice-Based Research Network (UTOPIAN) – to connect researchers to family care practitioners to answer important healthcare questions and translate findings into daily practice. Currently over 1400 family physicians are part of UTOPIAN. Dr. Greiver leads UTOPIAN as the Director and has plans to grow the network from a patient population of 600,000 to 2 million in the next 5 years. UTOPIAN’s large scale data has the potential to support an impressive scope of research.
Technology – particularly Electronic Medical Records (EMRs) – plays a foundational role in providing better care and improving knowledge translation across the community. EMRs provide physicians with better and more timely access to clinical information. For example, instead of searching through multiple filing cabinets for a patient’s medical history, a physician can easily download imaging reports, medication profiles and laboratory results with a click of a button. In addition, EMRs serve the broader community as clinicians have the ability to run population-based reports that can assist in supporting overall better community health.
Using data extracted from EMRs, Dr. Greiver and her team at UTOPIAN have built a researchable database of de-identified patient records called Safe Haven. “UTOPIAN is all about collaboration. Through Safe Haven we have the data and UTOPIAN provides the connections to help recruit people to research studies that will benefit the population,” says Dr. Greiver. In addition to increasing the Safe Haven database, Dr. Greiver is also looking for more opportunities to collaborate on studies in the primary care community.
The UTOPIAN and TDRA collaboration on the SARTAN-AD Study is an impactful first step in this direction. The study compares the ability of two approved medications for high blood pressure to slow down the progression of Alzheimer’s disease. Learn more about this partnership. In addition, UTOPIAN is deeply engaged with Diabetes Action Canada. Together their goal is to actively involve people living with diabetes when designing and implementing research. Learn more on UTOPIAN’s efforts in practiced-based research.
While Rome wasn’t built in a day, Dr. Greiver understands that knowledge translation take time and the biggest challenge might just be that implementing change to an existing system is very difficult. Perhaps the key to implementing this “diffusion of innovation”, as Dr. Greiver describes knowledge translation to be, is to foster and encourage change agents to come forward. At the end of the day, knowledge translation is all about communication and the change agent is someone influential who has the ability to efficiently and effectively communicate to people who can implement change into practice.
The TDRA is very fortunate to work with a vast spectrum of leaders and change agents in the fields of education, research, brain medicine, psychology, family care and beyond. We invite you to visit our blog regularly to learn more on the many outstanding individuals part of the TDRA.
Dr. Kumar is a scientist and psychiatrist at CAMH. His passion for dementia research stems from his intellectual curiosity to understand different functions of the brain. As a psychiatrist he is interested to investigate behavioural symptoms in relation to changes in the brain.
“Dementia is a major challenge for us all, particularly as dementia numbers are on the rise,” said Dr. Kumar. According to the Alzheimer Society, there are currently an estimated 564,000 Canadians living with dementia and that number will rise to 937,000 in 15 years. “Dementia not only impacts the patient but the entire family as well. The impact is that you lose your most prized possession – your sense of self and your connection to others”. It is this challenges that motivates Dr. Kumar to continue his work, particularly in research to find a cure to solve the dementia challenge.
“While the work is very difficult, the biggest misconception that surrounds dementia is that it is hopeless – it is not hopeless,” said Dr. Kumar. “We can make a tremendous difference in a patient’s life. We can treat some of their symptoms. We can put safety mechanisms in place to support patients.” Dr. Kumar stresses the importance of education about dementia, especially for family members to better understand the symptoms.
More research and data is needed to better understand the dementia patient population – this is the purpose of the TDRA Dementia Clinical Research Database which Dr. Kumar and TDRA colleagues lead. The Database Project, as it is also known, collects a standardized set of data among the dementia population and aims to help researchers understand the similarity and differences among various dementias. Learn more on the Database Project.
Dr. Kumar is also leading studies which investigate mild electric stimulation to the brain to treat agitation in dementia. Agitation affects up to 60% of Alzheimer’s disease patients. People experiencing agitation often show symptoms of anxiety and aggression. Preliminary results show that small electric charges to the brain may have positive effects on behaviour and cognition in Alzheimer’s disease patients. More details on the tTed Study. Another interesting study Dr. Kumar is working on is the S-CitAD Study which investigates the effectiveness of an anti-depressant medication, known as escitalopram, in treating agitation in dementia.
When asked the big question - how can we prevent risk of dementia? Dr. Kumar says, “What is good for the heart is good for the brain” and encourages us to adopt a healthy diet of low saturated fats with ample of fruits and vegetables and exercise. “Having a social network is also important for mental stimulation.”