Featured Researcher: Professor Paula Rochon

Dr. Paula Rochon is a geriatrician who is recognized for her work to focusing on dementia management of older adults, especially women. She is a senior scientist and the vice-president of research at Women’s College Hospital. Dr. Rochon leads Women’s Xchange, a research and exchange centre focussing on improving women’s health. She is also a professor at the University of Toronto in the Department of Medicine and Institute of Health Policy Management and Evaluation.  

We were fortunate to be able to interview Dr. Rochon about her work and ask her questions about her work.  

1. What brought up the issue of a need for dementia management research for different sexes?

It is important to consider sex and gender dimensions in all research because these factors serve an important role in affecting a patient’s health, their risk factors, how they experience health care and how health-care professionals provide care. When research studies do not report differences between women and men, we are left with a less valuable view of best practices for proper prescribing techniques, effective treatment methods and outcomes. Research that incorporates and reports data reflective of the whole population benefits everyone. As the Lead of Women’s Xchange, a knowledge translation and exchange centre based at Women's College Hospital designed to promote the development of women's health research across the province, it is a priority for myself and my team to reinforce the need to integrate sex and gender into research. With regards to dementia specifically, it is a condition that disproportionately impacts women. The burden of caregiving also falls more heavily on women, who are more likely to provide care for a parent, relative or spouse with dementia.

2. How is the care for older women with dementia different from men? What are some ways to improve the quality of care of different sexes?

Some of the work that we have done suggests that women are prescribed slightly lower doses of dementia medications relative to men. This may be because women require a lower dose to reduce the development of adverse events. Women generally live longer than men, which means that more women are living alone and may not have someone to provide care for them. This may explain in part why there are substantially more women than men in long-term care homes.

3. How have you seen the treatment of older adults improve over the years?

Over the years, there has been a growing recognition surrounding the importance of sex and gender considerations in research. Having better evidence that is tailored to women and men will result in better treatment for all Canadians. The inclusion of a sex-and-gender lens in health research creates evidence-based, effective and appropriate health-care policies for all.

4. What is the most important factor in improving the care of older adults with dementia?

Many older adults want to remain in their homes.  For this to happen, we need a lot more support in the community, particularly when it comes to caregivers. Caregiving has become increasingly taxing as many untrained people are providing medical and nursing care, assisting with daily living, and navigating the complexities of the health and long-term care system. As well, caregivers often provide financial support to their loved ones and may miss out on full-time employment, raises and other monetary benefits. Improving care for older adults with dementia starts with our caregivers.

5. What are prescribing cascades? What would you suggest doing to improve the issue of prescribing cascades?  

Prescribing cascades occur when a drug therapy leads to an adverse event that is misinterpreted as a new medical condition. This leads to the prescribing of a new drug therapy that may not be required. Prescribing cascades are particularly common in older adults, in part because they are a group that have more medical conditions and therefore may be prescribed more drug therapies. Prescribing cascades have also been identified with the drug therapies that are frequently used to manage dementia. One example is cholinesterase inhibitors, leading to incontinence, leading to the new prescription for a urinary anticholinergic.

 For more information on recognizing and managing prescribing cascades, you can access an article I co-wrote in the Lancet.

Research Update: Cognitive Impairments Reversed in Mice with Dementia

In hopes of finding effective treatments and possibly even a cure for dementia, scientists have been searching for ways to reverse memory deficits and impairments. For many years, advances in this area was challenging due to little knowledge about the cellular pathways which underlie dementia. However, promising research emerged in June 2018 when researchers at the Lewis Katz School of Medicine at Temple University were able to reverse cognitive impairments in mice with dementia. 

The study, published in the journal Molecular Neurobiology, showed for the first time in an animal model, that a drug can reverse tau pathology – the second-most important brain lesion in dementia patients. As senior investigator Dr. Domenico Praticò explains, “We show that we can intervene after disease is established and pharmacologically rescue mice that have tau-induced memory deficits.” 

The researchers discovered that dementia is related to damage to nerve cells from inflammatory molecules known as leukotrienes. The team then aimed to test if blocking leukotrienes could reverse the cognitive impairment in mice with dementia. This was done by injecting the mice with zileuton – a drug that inhibits the formation of leukotriene by blocking the 5-lipoxygenase enzyme. 

At the end of the 16-week treatment period, the mice were put into maze tests to assess their working and spatial learning memory. In comparison to the untreated animals, the tau mice that were injected with zileuton performed significantly better, suggesting that zileuton successfully reversed the cognitive impairment. 

In fact, the researchers found a 90% reduction in leukotrienes in the treated mice compared to the untreated group. As well, levels of phosphorylated and insoluble tau decreased by 50% in treated animals. Insoluble tau is known to directly damage synapses; thus, microscopic examination revealed severe synaptic deterioration in the untreated animals, while the synapses of the treated mice appeared to be undamaged. As said by Dr. Praticò, “Inflammation was completely gone from tau mice treated with the drug. The therapy shut down inflammatory processes in the brain, allowing the tau damage to be reversed.” 

More information on the study conducted by the team at the Lewis Katz School of Medicine at Temple University can be found here: https://www.sciencedaily.com/releases/2018/06/180608101905.htm

Featured Researcher: Professor Sandra Black

Professor Sandra Black is a world-renowned physician and researcher recognized for her work in dementia and stroke diagnosis and treatment. She is a University of Toronto Professor of Neurology, and a senior scientist and program director of the Hurvitz Brain Sciences Research Program at the Sunnybrook Research Institute. Professor Black is also the executive director of the Toronto Dementia Research Alliance (TDRA), and held the inaugural Deborah Ivy Christian Brill Chair in Neurology at Sunnybrook Health Sciences Center and University of Toronto (2006-2017). In 2015, she was appointed as an Officer to the Order of Canada for her contributions to stroke and dementia research. Professor Black is internationally recognized particularly for work showing relationships between silent stroke and Alzheimer’s Disease. 

We were fortunate to interview Professor Black and ask her questions about her research. 

What is the most rewarding part of being a researcher? 

One of the most rewarding aspects of being a researcher for Dr. Black is to be on the front line of new treatments and discoveries. For example, she does clinical trials, some sponsored by drug companies to test out new treatments for dementia, and some to repurpose existing drugs when they may be potentially useful in another disease, for which they were not initially intended. For example, some high blood pressure medications may be preferable for hypertensive Alzheimer’s Disease (AD) patients, so Dr Black is conducting a trial to compare the effectiveness of two commonly use blood pressure drugs that are equally good for hypertension control in slowing down brain shrinkage in AD. Dr. Black explained that as a researcher, you are always learning and collaborating with others to help understand mechanisms and improve care. She finds it rewarding to be able to “give back” adding new knowledge to the field and sharing it with others. 

What is your latest research study about dementia? 

Dr. Black is very optimistic about the future of dementia research and research for other mental and neurological conditions. She describes it as a very “interesting era” and an “exciting time” in dementia research. She is currently involved in a clinical trial that is investigating how to remove and slow amyloid protein depositing in the brain in people before they have any memory symptoms. Participants come in for a monthly infusion aimed at removing amyloid protein from the brain and preventing its accumulation, which can eventually lead to memory loss and dementia. It is a double –blind controlled trial meaning patients are randomized to active drug or placebo without anyone knowing which drug they are on, unless of course some problem arises.

How have you seen dementia treatment and research evolve in your years of working as a researcher? 

At the beginning, Dr. Black explained how the focus of research was on learning the causes and components of the dementing illness, examining the proteins in the brain, and investigating the pathology. However, as the disease has become increasingly prevalent with an aging population, research and treatment has intensified and advanced. Dr. Black in collaboration with other research colleagues and radiologists helped developed an MRI protocol in her clinic long ago which allowed them to scan the brain and quantify brain shrinkage and also small vessel disease, which shows up as small strokes or as white spots and patches on MRI scans. Additionally, she has been involved in researching the genetic and hereditary side to dementia. There have also been advancements in using PET scans to see protein deposits in the brain that previously were only able to be seen at autopsy. Now, there is also research into vascular risk factors and lifestyle choices that contribute to the development of Alzheimer’s disease and stroke. For example, hypertension control is important for preventing dementia developing, and a history of a high level of physical exercise especially in teen age and through all the decades of life was found to be associated with better performance on cognitive tests, when those same people were assessed in their 80s. 

Congratulations on receiving the Order of Canada for your research! Have you seen your research impact the way that dementia is diagnosed and treated? 

Dr. Black explained that in the past, dementia research had been focused primarily on the amyloid protein, which deposits in the brain and can be associated with dementia. However, coming from a research background in stroke and dementia, Dr. Black wanted to better understand the role of other factors, such as the brain’s blood vessels, in developing dementia. She began to explore how the brain builds resilience and tries to combat the gradual loss of functional neural networks in neurodegenerative diseases such as Alzheimer’s by careful quantitative assessments of clinical and brain imaging in a research partnership with her memory clinic patients, also including genetics, and her team’s findings have influenced other research and treatment approaches earning her the well-deserved appointment to the Order of Canada. 

            

Read more about Professor Black’s work:

 https://sunnybrook.ca/research/team/member.asp?t=10&m=28&page=1212

Research Update: Slowed Brainwaves are Early Signs of Dementia

To catch dementia and Alzheimer’s disease early on, scientists are looking for effective signs to use to diagnose dementia earlier. According to recent findings from researchers at the University of Toronto and Baycrest Rotman Research Institute, tracking a person’s brainwave activity can give clues of early signs of dementia.

The study examined the electrical activity and brain structures of 64 adults when they were in a resting state. Magnetoencephaolography (MEG) was used to measure brainwaves and their location, and magnetic resonance imaging (MRI) was employed to determine the magnitude of loss of brain cells. The participants were also evaluated for their cognitive abilities. 

The study, published in the journal Human Brain Mapping, suggested that brainwave activity tends to slow down in certain brain regions that are likely to be affected by dementia next. The team of researchers identified slowed brainwaves and subtle signs of damage in the brain areas in charge of memory and planning, in both individuals with mild cognitive impairment and those with primary progressive aphasia – a rare form of language dementia. Although these individuals were only observed to display minor memory and thinking problems, their slowing brainwaves predicted the severity of their cognitive impairment, including the degree of memory loss.

Jed Meltzer, the senior author of the study and Canada Research Chair in Interventional Cognitive Neuroscience, explains that, “By using brain imaging, we were able to pinpoint that this slowing of electrical activity occurs in specific regions that have not yet lost brain cells, but are negatively affected by the disease. This means that these areas could be more responsive to treatments since the brain cells have not died yet and are only starting to undergo damage.” In essence, slowed brainwaves can act as a sign of when brain cells begin to malfunction and may allow for new targeted brain treatments to be implemented early on.

The team aims to continue exploring and validating the use of brain activity as a reliable biomarker for early signs of dementia. More information about this study can be found here: https://www.utoronto.ca/news/u-t-study-links-slowed-brainwaves-early-signs-dementia

Featured Researcher: Professor Krista Lanctot

Dr. Krista Lanctot is a professor Psychiatry and Pharmacology at the University of Toronto. Dr. Lanctot it the executive director of MORE research group at Sunnybrook Health Sciences Centre. She has her PhD Clinical Pharmacologist and is working in the Hurvitz Brain Sciences Research Program. She is known for clinical trials involving patients with dementia and the treatment of agitation and aggression, as well as apathy. We were fortunate to be able to talk to Dr. Lanctot about her work in the questions below.

1. What sparked you interest in dementia research? Can you tell us more about the research you do?

When I first came to Sunnybrook, there were no medications for Alzheimer’s disease, and people with behavioural problems were still being given sedating medications.  With my PhD in Clinical Pharmacology, I thought that there must be a better way to help these people. I decided that the key missing pieces were understanding the underlying neurobiology of the behaviours, and personalizing treatment. I lead a large lab whose goal is to optimize drug treatments by doing just that.  We look at the behaviours, brain and biomarkers, and use that information to suggest and test new treatments for Alzheimer’s disease and other dementias.  My group also looks at early neurobiologic changes that precede dementia, and are now testing an intervention that may prevent these devasting yet common diseases.

2. What is the most challenging part about your research?

The most challenging part is the ongoing need to secure funding in this era of increasing budgets and complexity with shrinking availability of research funds.

3. Over the years, how have you seen the treatment of agitation and aggression improve? What is currently being done to treat these symptoms in people with dementia?

We are now using a wider armamentarium of medications, and no longer rely on sedation. There have been big improvements.  We are also testing new medications, but now use the more personalized and rational approach that my group and others have now championed. Our most recent discovery was that low doses of synthetic THC can help with agitation and aggression.

4. Apathy is a common issue faced when working with people with dementia. What is the underlying cause? What can be done to engage them?  

There are lots of underlying causes of apathy because whole brain circuits have to be in tact to promote motivated and goal-directed behavior.  The first step is always looking at the environment.  After that has been optimized, we also look at prescribing medications. My group showed that the deficits in the dopaminergic brain reward system were contributing to apathy, and more recently that the pro-dopaminergic drug methylphenidate could help some dementia people by improving apathy.

Read more about Dr. Krista Lanctot here: https://sunnybrook.ca/research/team/member.asp?t=11&page=172&m=102

Research Update: Using Synthetic Cannabis as Treatment for Agitated Alzheimer's Patients

In July 2018, Canadian researchers from Sunnybrook Health Sciences Centre presented some encouraging data which suggested that a synthetic form of cannabis, called nabilone, may help calm agitated patients with Alzheimer’s.

Approximately one-quarter of patients with advanced Alzheimer’s experience agitation – where they can become angry, restless, and verbally or physically abusive – and thus are often the primary reason that patients are sent to hospitals or institutions. Current treatments for agitation use anti-psychotic drugs; however, these drugs have only modest effects and are associated with a number of side effects, such as higher risks of strokes, falls, and death.

The team of scientists at Sunnybrook tested the efficacy of the synthetic cannabis in 38 patients with moderate to severe Alzheimer’s who had noticeable agitation over a 14-week trial. They found that while patients were on the nabilone, both agitation and overall behavioral symptoms improved significantly, in comparison to the placebo. In fact, “They wouldn’t strike out, they wouldn’t get stiff when care was being provided. They were easier to examine and were calmer and more comfortable,” said Dr. Nathan Herrmann – a psychiatrist and scientist with Sunnybrook and the University of Toronto. Moreover, the synthetic cannabis seemed to also have a positive effect on caregivers by reducing their stress of looking after the patient.

The Canadian researchers have said that their next steps are to plan a larger study with more patients and to determine the correct dose of nabilone for patients, in order to minimize sedation.  

More information about Sunnybrook’s research can be found here: https://www.ctvnews.ca/health/form-of-cannabis-may-have-calming-effect-on-agitated-alzheimer-s-patients-1.4025475

Featured Researcher: Professor Carole Cohen

Professor Carole Cohen is a University of Toronto Professor of Psychiatry and Head of the Division of Geriatric Psychiatry. She is an affiliate scientist in the Evaluative Clinical Sciences, Hurvitz Brain Research Program at the Sunnybrook Research Institute. Professor Cohen’s work and research is focused on helping patients, their families, and their professional caregivers manage dementia diagnoses making her an expert in dementia service care. She is well known for her involvement and advocacy for dementia patients in legal capacity and consent issues. 

We were fortunate to have the opportunity to interview Professor Cohen about her work: 

1. Can you tell us about your research with dementia caregivers? 

My research started out with a study examining risk factors for individuals with dementia moving from home into another care setting. As part of this study, I had the opportunity to visit people with dementia living at home and talk with those assisting them. I became interested in the caregiver’s experience and how it affected not only their health but the experience of those they cared for. It became clear that not all caregiver experiences were negative and many found great comfort and meaning from their caregiving role. I worked with others to better understand these positive effects of caring and how they might influence caregiver decisions. I was also part of a team that studied pathways to diagnosis for families from different cultural backgrounds across Canada.

2. What is the most rewarding part of your work in this field as a scientist? 

For me personally learning from individuals with dementia and their families and being able to share my knowledge with others is the most rewarding aspect of my work. I enjoy translating research findings into accessible language to help clinicians, policy-makers and other researchers better understand the dementia experience. 

3. How has dementia management evolved in your years of working as a researcher?

Dementia management has evolved dramatically since I started practising. Whereas it was initially difficult to find dementia specific services, they now exist everywhere in Ontario. They are more likely to put the individual with dementia at the centre of care planning with programs for those with special needs (such as early-onset dementia) and focus on personhood and dignity. Support groups and advocacy groups for individuals with dementia are relatively new. Holistic approaches that focus not only on anti-dementia medications but diet, exercise, appropriate activities are more readily available. Programs also provide assistance for longer periods of time with earlier diagnosis and increased attention to needs at the end of life. 

4. Dementia is an illness that not only impacts the individual, but it also impacts family members. From your experience, what advice would you give to our readers who have a loved one with dementia?

Family members play a vital role in supporting individuals with dementia. It can be a rewarding and exhausting role. In dementia care families have to simultaneously optimize the current situation and plan for a future when the disease will progress and the person with dementia needs will change. I would urge family members to be mindful of three major areas they should address. Firstly, they need to understand what dementia as an illness means, how it affects their family member and how it is likely to progress. Education and knowledge are important if one is to understand why a relative is behaving in certain ways and how to best support them. Secondly, family members need to address their own psychological and physical needs – caregiving can be stressful and caregivers need to take time for themselves and learn how to cope with these demands. This may mean learning new techniques such as Mindfulness, accessing individual or group counselling and paying attention to their physical health, diet and exercise. This leads to the last part of the triad which is asking for help and ensuring that caregivers have adequate social support. Caregivers need to build a support team of professionals, family and friends and learn how to effectively ask them for help. 

Read more about Professor Cohen here: 

https://sunnybrook.ca/research/team/member.asp?t=10&m=47&page=527