Scientist Explains With Dr. Rajji: What are Inclusion and Exclusion Criteria?
May 27, 2021
The inclusion criteria for a clinical trial are carefully selected parameters used to include or recruit people into a study. Researchers may look for people with specific condition(s) (e.g., moderate to severe Alzheimer’s disease), ages, ethnicities, or other attributes to join their study.
Clinical trials also have exclusion criteria. These are carefully selected parameters that researchers use to exclude or prevent people from joining their study. There are a number of reasons why researchers may have specific exclusion criteria.
- Example of exclusion criteria based on condition(s): In clinical trials for people with Alzheimer’s disease, a diagnosis of schizophrenia may be part of the exclusion criteria because this condition can itself lead to memory problems. This makes it difficult for researchers to know what is causing the memory problem and whether the treatment may be beneficial. Instead, people with schizophrenia may look for studies with inclusion criteria of schizophrenia with or without memory problems.
- Example of exclusion criteria for safety reasons: Clinical trials exclude people who also have conditions that make it unsafe for them to receive the treatment being tested. For example, in studies testing transcranial magnetic stimulation (TMS), people are often excluded if they have metal pieces in their head as the magnetic fields generated by TMS such may shift the pieces and cause harm to the participant.
- Example of exclusion criteria based on medication(s): Clinical trials also exclude people who are taking medications that may prevent the treatment being tested from being effective. For example, anti-seizure medications may be part of the exclusion criteria for a clinical trial with brain stimulation. This is because these medications can alter the brain in a way that interferes with the effects of brain stimulation approaches such as TMS. By having these exclusion criteria, researchers can ensure that the outcomes of this study are due to the brain stimulation.
Scientist Explains With Dr. Rajji: What are Randomized Control Trials?
April 14, 2021
Randomized Controlled Trials (RCTs) are clinical studies in humans that test whether a proposed treatment is beneficial and whether its benefits outweigh the harms or side effects.
Let’s consider an example where a clinical trial is testing a treatment X. The trial will typically include two groups, group A and group B. People assigned to Group A receive the treatment X that is being tested, which might be a drug, medical device or lifestyle program. People in Group B are the comparison group, where either they receive a “placebo” (i.e., no active treatment) or another typical, well-established treatment for the condition (let’s call this treatment Y) to test whether treatment X works better than or as well as treatment Y. A placebo typically “looks” like the active treatment but has no significant effects. For example, a clinical trial testing a drug for the treatment of Alzheimer’s disease might have a placebo that is a pill with the same colouring, sizing and labelling as the active drug, but with no active ingredients.
What does “randomized” mean? This means people in the study are randomly assigned (e.g., deciding by a “coin flip”) to Group A or B. So if there are 100 people in the study, 50 people would be randomly assigned to group A and 50 to group B. This helps to ensure the groups are as similar as possible in their age, gender, and other relevant attributes.
What does “controlled” mean? These clinical trials have at least one “control” or comparison group (e.g., Group B) where participants receive a placebo or the typical care for their condition. This helps researchers compare whether the proposed treatment X is safer and more effective than what the control group receives.
What does “blinded” mean? Participants and research team members—particularly those who are assessing the participants and those who analyze the outcomes of the trial and care for participants—are blinded to the treatment conditions. This means that they are unaware of whether a participant is receiving the treatment X being tested (i.e., they are in Group A) or not (i.e., they are in Group B). Blinding ensures that this knowledge does not influence the outcomes of the study. Blinding is only broken after the trial is complete or if there are safety concerns.
Scientist Explains With Dr. Collingridge: How Are Memories Made?
February 17, 2021
The brain has about 100 billion cells known as neurons. These neurons are all connected and “talk” to one other, which makes it possible for us to do our daily activities. In the brain, the place where one neuron ends and is connected to another neuron is called a synapse. A synapse is where neurons talk to one another.
At most synapses in the brain, the neurons talk to each other using a chemical known as a “neurotransmitter.” The most common neurotransmitter in the brain is known as L-glutamate. When one neuron talks to another, the first neuron releases L-glutamate into the synapse. The second neuron has proteins on its surface (called receptors) that are ready to receive the L-glutamate. Once the L-glutamate acts on the receptor, the second neuron receives the signal and becomes activated. The receptors involved in this process are known as AMPA receptors.
Canadian psychologist Donald Hebb proposed that learning is due to the strengthening of the synapses between the neurons in the brain in response to patterns of neural activity. Tim Bliss was a graduate student at McGill and when in search of so-called Hebbian synapses. In Oslo he found them by discovering the process known as long-term potentiation (LTP).
We now understand LTP at the molecular level. The synapse gets stronger because more AMPA receptors are inserted into the synapse leading to a bigger signal in the second neuron that is “listening”. This process is known as synaptic plasticity and is responsible for our learning. For instance, this process is involved when you can pick up playing piano more quickly after practicing, since the connections between the neurons that are active when you play piano are stronger.
The NMDA receptors, a second type of glutamate receptor, do not typically contribute to this communication. Instead they stay largely inactive until there is a period of more intense activity or talking between neurons. They are then temporarily awoken where they serve as the trigger for LTP, which is the process for how we form memories. This means at the level of the synapse, we can say that NMDA receptors are for learning and AMPA receptors are for memory.
Considerable work by many groups worldwide have built upon this simple concept and have shown that this type of mechanism occurs as we learn and remember. Notably, Richard Morris showed that blocking the NMDA receptors led to learning and memory problems in mammals.
This process is also key to understanding how the drug memantine (Namenda) works. This drug is the second class of drug approved by Health Canada for the treatment of Alzheimer’s disease and works by blocking the NMDA receptor.
Research has shown that not only blocking the NMDA receptor prevented LTP but also that over-stimulating the NMDA receptor prevented LTP. This latter process seems to occur in Alzheimer’s disease. By blocking the NMDA receptor in people with Alzheimer’s disease with a drug like memantine, this can help to restore LTP when it is being prevented by over-stimulation of the NMDA receptor.
Unfortunately, however, memantine’s effectiveness is limited to a short-term improvement in thinking and memory and is only effective in some people with Alzheimer’s disease. Ongoing research is currently looking into better ways to modify NMDA receptor activity and LTP to improve thinking and memory for longer periods of time and with fewer side effects.
Virtual dementia care and the challenges of the COVID-19 pandemic
December 21, 2020
Dr. Morris Freedman has dedicated his career to tackling dementia, both through his clinical work and his research. His clinical career — which began with Medical School at the University of Ottawa, Neurology residency at the University of Toronto and a Behavioural Neurology fellowship at the Veterans Administration Medical Centre in Boston — has been dedicated to enhancing care for people living with dementia.
As the Head of the Division of Neurology and the Medical Director of Cognition & Behaviour at Baycrest, Dr. Freedman has continued this clinical work while adapting to the challenges of the COVID-19 pandemic. Throughout the pandemic, he has found ways to enhance care for people living with dementia both in his clinic and in the community.
Virtual dementia care during the pandemic
At the start of the pandemic, Dr. Freedman switched to providing virtual care to his patients in line with safety regulations. This also meant he had to adapt thinking and memory tests to be done over the computer.
One such test is the Behavioural Neurology Assessment – Short Form, referred to as the BNA-SF. The BNA-SF is a 20-30 minute test typically used for patients in the mild to moderate stages of dementia. It assesses a patient’s attention, memory, language, ability to complete complex tasks, and understanding of the space around them.
Previously, this test would be given in-person during a clinic visit, but is now done virtually. Using the Ontario Telemedicine Network, Dr. Freedman and his team first connect with patients in their own homes by computer. Then, Dr. Freedman’s clinical team will enter the patient’s responses or take photographs of written activities as the patient holds them up to the screen. The staff member enters this information using an iPad that automatically uploads it into the Dementia Clinical Research Database for research purposes, with the patient’s consent.
Dr. Freedman and his team are also looking at ways to offer the Toronto Cognitive Assessment (TorCA) virtually, a more in-depth assessment that was developed from the BNA-SF.
“The TorCA is a cognitive assessment tool designed for use by trained physicians, nurses and other healthcare professionals to be administered in any clinic setting,” says Dr. Freedman. “The TorCA was built on the Behavioural Neurology Assessment and by expert opinion, we added items that we expected would discriminate between different types of disorders.”
While working to find ways to administer the TorCA virtually, Dr. Freedman has since been successfully delivering the BNA-SF and other thinking and memory tests over the Ontario Telemedicine Network, and sharing his knowledge with fellow neurologists across Toronto to help with their own practices. Training on how to virtually administer the BNA-SF and other thinking and memory tests are available to healthcare providers by registering for the Members section of our website.
Beyond his own practice, Dr. Freedman and his colleagues have also helped to enhance clinical care for people with dementia in the community during the COVID-19 pandemic. He recently led the creation of Baycrest’s Virtual Behavioural Medical Program which is a collaborative partnership between the Baycrest Sam and Ida Ross Memory Clinic and Toronto Central Behavioural Support for Seniors Program (TC BSSP).
The goal of this program is to prevent unnecessary emergency room visits as a result of responsive behaviours (e.g., agitation and aggression) in people with dementia. The program uses a virtual platform to connect Dr. Freedman with patients in long-term care homes, acute care hospitals, and community care settings. He then provides virtual assessments and management that support staff and families in addressing responsive behaviours. To date, the program has had great success in reducing hospital admissions, providing support to clients and caregivers, and fostering collaborations with healthcare partners.
To learn more about Dr. Freedman and Baycrest’s Virtual Behavioural Medicine Program, please visit: https://www.baycrest.org/Baycrest-Pages/News-Media/News/Baycrest-Health-Sciences/Baycrests-Virtual-Behavioural-Program.
Using light technology to turn back the clock on Alzheimer’s disease
August 13, 2020
Many researchers are looking at ways to stop or slow Alzheimer’s disease using new and innovative technologies. This includes TDRA’s Clinical Research Core member Dr. Corinne Fischer, who is leading a multi-centre study testing a medical device developed by the Canadian biotechnology company Vielight Inc. The device is called the “Neuro RX Gamma Photobiomodulation Device,” and it aims to treat Alzheimer’s disease.
The device is a non-invasive headset with a nose clip that delivers low-energy, near-infrared LED light through the skull and the nose to the brain. Dr. Fischer, who is currently the Director of Geriatric Psychiatry at St. Michael’s Hospital and an Associate Professor of Psychiatry at the University of Toronto, has been leading the clinical trial to test whether Vielight’s wearable technology can improve thinking, memory and quality of life in people aged 50 and older with moderate to severe Alzheimer’s disease.
With a goal of having clinical trials running at 8 sites across North America, there are currently 2 sites that are set up in Toronto and actively recruiting patients. As part of the study, participants are asked to wear the headset for 20 minutes per day, 6 days per week for a period of 6 months, during which Dr. Fischer’s research team will reassess their thinking, memory and quality of life. The trial is being coordinated by the Applied Health Research Centre at St. Michael’s Hospital and is expected to be complete by 2022.
And what does the research say about light therapy? According to Dr. Fischer, initial studies in humans show that this non-invasive light therapy can stimulate mitochondria, the part of the brain cell that produces energy, and promote gene expression that can protect the brain. Initial studies in laboratory models have shown that light therapy can also target the amyloid-beta and tau proteins that deposit in the brains of people with Alzheimer’s disease. Two published pilot clinical studies support the potential effectiveness of the device.
Inspired to get into Alzheimer’s research to solve unanswered questions and help those with the condition, Dr. Fischer sees the potential benefits that clinical trials can have for people with Alzheimer’s disease: “This is an opportunity to determine if we can use technology and our knowledge about light therapy (photobiomodulation) to see if it will help improve cognition in Alzheimer’s patients with moderate cognitive impairment, and help address perhaps some of the behavioural symptoms associated with dementia as secondary outcomes. That’s the goal - to see if it can turn back the clock on this neurodegenerative disorder.”
Having completed medical school at the University of Toronto, her residency and fellowship training at McMaster University, and then conducting research at St. Michael’s Hospital for over 20 years, Dr. Fischer knows the ins and outs of dementia care and research. Although she admits research in the field of Alzheimer’s disease can be challenging at times, she is hopeful about the future and what research on light technology could reveal. There is currently no drug or medical device that can stop the course of Alzheimer’s disease, but Dr. Fischer hopes that her research could help provide an effective treatment option for people living with Alzheimer’s disease in the future.
Responding to the COVID-19 Pandemic
June 8, 2020
For the last few months, the world has been facing the new realities brought about by the COVID-19 pandemic, impacting nearly all aspects of life. People with dementia and their caregivers are particularly vulnerable at this time as access to both care and support services may be limited as a result of social distancing measures. We wanted to share some of the work we are doing to support people with dementia and their families during this difficult time, as well as some COVID-19 resources and services that may be helpful.
TDRA Site Clinicians and Researchers
The Toronto Dementia Research Alliance (TDRA) works together with the University of Toronto and five Toronto memory clinics located at Baycrest, Centre for Addiction and Mental Health (CAMH), Sunnybrook Health Sciences Centre, University Health Network, and St. Michael’s Hospital. Each of these organizations is helping to stop and prevent COVID-19 through care practices, including offering virtual care to patients with cognitive and memory disorders like Alzheimer’s disease, and through innovative research. Here are some examples of early adoption of initiatives that are being put into place at our partner sites to continue care and research during this global pandemic.
Dr. Morris Freedman at Baycrest, together with Behaviour Supports Ontario (BSO), is leading work with 36 long-term care (LTC) homes across the Toronto Central Local Health Integration Network (LHIN) to provide support for individuals who have responsive behaviours such as agitation and aggression. Dr. Freedman and his team are providing virtual video and phone consultations, and follow-ups on LTC clients to help manage these behaviours and prevent emergency room visits. Consultations often also include family members, who offer insights into their loved one’s behaviours and ways to help.
In addition to this work, Dr. Freedman is seeing patients by video through his memory clinic practice at Baycrest. Using the Ontario Telemedicine Network, Dr. Freedman hosts virtual visits for new referrals and follow-ups for his patients with cognitive disorders, ensuring that their care continues during the COVID-19 pandemic. He is pioneering the use of virtual care tailored to the needs of people with dementia and has provided training to neurologists across Toronto on how to carry out cognitive screening tests by video, so more patients can benefit from this innovation in care.
Dr. Tarek Rajji and his team in the Adult Neurodevelopment and Geriatric Psychiatry Division at CAMH are providing outreach support to 21 LTC homes in mid- and west- Toronto. They provide older adult psychiatry and mental health nursing expertise, both virtually and in-person, to help LTC workers address mental health problems in older adults. They also plan to offer educational sessions, tools and technologies to help staff manage behavioural symptoms of dementia; technical support to assist staff in optimizing virtual care; and virtual coaching and mental health support sessions for frontline staff.
Based on their experience, Dr. Rajji along with Drs. Eric Brown, Sanjeev Kumar, Bruce Pollock and Benoit Mulsant recently published an article on the impacts of COVID-19 for older adults with dementia, and ways to address these impacts. Their goal for this publication is to raise awareness about the needs and challenges of people living with dementia during the pandemic among researchers and clinicians alike.
In addition, CAMH researchers are planning to launch new research projects aimed at better understanding the impacts of the COVID-19 pandemic on older adults in the community and preventing COVID-19 infection among high-risk older adults.
Based on preliminary evidence that COVID-19 may invade the brain and also can cause stroke, TDRA members on investigative teams from Sunnybrook Research Institute and Rotman Research Institute have received funding from the Sunnybrook Foundation to perform Magnetic Resonance Imaging (MRI) using a protocol sensitive to subtle brain changes and stroke, as well as smell tests and sensitive neurocognitive assessments, to identify the effects of COVID-19 on the brain. Learn more about NeuroCovid19: brain imaging of survivors study.
The Canadian Consortium on Neurodegeneration in Aging (CCNA) led by Dr. Howard Chertkow, with nearly 325 researchers dedicated to finding a cure for dementia, has also been involved in a number of COVID-19-related initiatives. CCNA researchers have participated in several committees created to respond to different issues raised by the pandemic, including the effects on their current research and new research opportunities. In addition to these committees, the CCNA is also part of the COVID-19 and Dementia Task Force, which was convened by the Alzheimer Society of Canada to improve care for people living with dementia and reduce stigma and discrimination.
Although the pandemic has put a hold on in-person clinical assessments, such as MRIs, cognitive tests, and blood and saliva sample collection, some assessments using questionnaires can still be conducted over the phone. In line with safety practices, CCNA researchers are leading many COVID-19- and dementia-related research projects including:
- establishing guidelines for emergency room and intensive care unit communication and monitoring practices, including the use of telehealth (virtual) assessments and tests for patients
- researching ways to address both intensive care practices and ethical issues for people living with dementia who develop COVID-19
- studying the many impacts of COVID-19 on LTC homes, including one study that will compare the results of surveys done both before and after an outbreak
- assessing COVID-19 mortality rates in people living with dementia
- developing community guides for rural settings and Indigenous communities, which will be offered in many languages, as well as toolkits for caregivers and family members.
Learn more about CCNA’s ongoing COVID-19 initiatives.
All together, we are hopeful that these clinical and research-embedded-in-care projects will increase our knowledge about COVID-19 and the ways to prevent and treat it in the near future.
TDRA Coordinating Core
During this time, TDRA’s Coordinating Core team has continued to work virtually to ensure projects continue without delay wherever possible. The team is focused on:
- providing outreach and education about research to the public
- working with the Patient and Family Advisory Council to build trust in research
- increasing connections among Toronto neuroscience researchers
- supporting the management of dementia in primary care (i.e., family doctors)
- helping researchers across the city start their work more quickly
- supporting recruitment and engagement of participants in research.
COVID-19 Resources and Services
We would like to express our thanks to all healthcare workers for their hard work, dedication and compassion in keeping us safe and healthy during this pandemic.
With the surge in need and workload for healthcare workers, it is vitally important that healthcare workers get the mental health supports that they need. A number of resources and online services are available to support healthcare workers, including:
- Centre for Addiction and Mental Health: https://www.camh.ca/en/health-info/mental-health-and-covid-19/information-for-professionals
- Canadian Psychological Association: https://cpa.ca/corona-virus/psychservices/
- Government of Ontario: https://www.ontario.ca/page/covid-19-support-people#support-health-care-worker
- Canadian Consortium on Neurodegeneration in Aging: https://ccna-ccnv.ca/covid-19-useful-resources1/
- Hospice Palliative Care Ontario - 1‐866‐485‐4204 or https://www.hpco.ca/grief-and-bereavement-supports-for-health-care-workers/
- Public Health Ontario: https://www.publichealthontario.ca/en/diseases-and-conditions/infectious-diseases/respiratory-diseases/novel-coronavirus/health-care-resources
- University of Toronto Faculty of Medicine: https://medicine.utoronto.ca/node/3544
- University of Toronto Department of Medicine: https://www.deptmedicine.utoronto.ca/covid-19-wellness-resources-faculty-and-trainees
You do not need to go through this alone – these services are here for you, just as you are here for us. Thank you for all that you do.
People living with dementia and their care partners
This can be an especially difficult time for people with dementia and their care partners for many reasons, including social isolation and changes in access to supports. Whenever possible, it is important to stay connected virtually, stay active and get support when needed. Some resources to help you and your loved one(s) during this time include:
- Reitman Centre/Enhancing Care for Ontario Dementia Care Partners: https://www.dementiacarers.ca/learning-resources/helpful-resources-for-dementia-caregivers-during-covid-19/
- Alzheimer Society of Canada: https://alzheimer.ca/en/Home/Living-with-dementia/managing-through-covid-19
- Parkinson Canada: https://www.parkinson.ca/connexion/
- Heart & Stroke: https://www.heartandstroke.ca/articles/coronavirus-the-information-you-need
- Ontario Neurodegenerative Disease Research Initiative: https://ondri.ca/care-partner-resources/
- Canadian Consortium on Neurodegeneration in Aging: https://ccna-ccnv.ca/covid-19-useful-resources1/
- Toronto Seniors Helpline: https://torontoseniorshelpline.ca/ or 416-217-2077
- University Health Network Memory Clinic: https://www.uhn.ca/KNC/Clinics/Memory_Clinic/Documents/COVID-19-Resources-Patients-Caregivers.pdf
- The Association for Frontotempoal Degeneration: https://www.theaftd.org/navigating-ftd-long-term-care-during-the-covid-19-pandemic/
We also encourage you to connect with your local community organization(s) to find out what programs, services and resources are available during this time to support you.
Dementia Clinical Research Database
March 2, 2020
How can we better understand the similarities and differences between different types of dementias? One important way is by gathering the same health information and administering the same tests on patients with different dementias across Toronto’s academic memory clinics. This is what is currently being done through the Dementia Clinical Research Database project, co-led by Dr. David Tang-Wai, Associate Professor in Neurology and Geriatric Medicine at the University of Toronto, Co-Director of the University Health Network’s Memory Clinic, Clinical Investigator at the Krembil Brain Institute and a member of TDRA’s Clinical Research Core.
For many years, Toronto’s academic memory clinics at Sunnybrook Health Sciences, Baycrest, the Centre for Addiction and Health, University Health Network, and St. Michael’s Hospital were collecting different types of information and test results from patients with dementia. To standardize this collection, the Toronto Dementia Research Alliance’s executive and researchers ꟷ including Dr. Tang-Wai, Dr. Morris Freedman from Baycrest, Dr. Sanjeev Kumar from the Centre for Addiction and Mental Health, and Dr. Sandra Black from Sunnybrook Health Sciences and TDRA's current Executive Director ꟷ all worked together to create a standard tool to assess dementia known as the Toronto Cognitive Assessment (TorCA). The TorCA takes about 30-40 minutes to complete and detects the early stages of memory impairment by testing various aspects of thinking, such as memory, language, visuospatial abilities, multitasking and attention.
To make the TorCA results available for research purposes, these data needed to be stored and accessed electronically. With funding from Brain Canada, Dr. Tang-Wai co-led the creation of the Dementia Clinical Research Database.
As highlighted by Dr. Tang-Wai, “The database is an example of research embedded in clinical care. Where a person will come in and see us for a medical evaluation to diagnose their type of problem, but at the same time we are collecting information in real time for research.” Currently, standardized patient data – including age, gender, ethnic background, diagnosis, years of education, language, and memory test results – are being input into the database with the patient’s consent.
Most recently, Dr. Tang-Wai and colleagues developed the TorCA on the iPad, making it easier for clinicians to record and take images of cognitive tasks completed by patients. This, along with additional health care information, will be done with tablets in real-time, allowing the results to be directly uploaded to the database. This initiative, which is expected to be completed by the end of 2020, will make the collection of patient data more efficient; remove a data entry step that can create errors; and add new measures to the assessments, including the time the patient takes to complete a task.
According to Dr. Tang-Wai, the potential applications for the future are quite large. The database will help clinicians learn more about dementia and receive patient data in real-time, which could lead to a faster diagnosis. It can also provide a real world look at people with dementia, including the co-occurring disorders they experience. Having larger numbers of people with dementia within the database could also help clinicians match people with dementia to clinical trials that may be of interest.
Dr. Tang-Wai also sees the impact of this work extending beyond Toronto: “If we can demonstrate this in the Greater Toronto Area, we can then expand across Canada and even have links to the United States, United Kingdom, Japan, and beyond. This larger dataset will allow us to view differences and commonalities in dementia across geographical locations, and to make rare diseases such as some atypical dementias not as rare and easier to study.”
To learn more about the Dementia Clinical Research Database, please visit: https://tdra.utoronto.ca/studies/.
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 TDRA and UTOPIAN 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.”