Big sister Debbie has always been there for Cindy; this time, as they scurry through hospital corridors, a little late for their first appointment of the day.

Together, the siblings navigate traffic, banter over the long drive from Brantford, and keep on top of appointments. Debbie is a little on edge, given the circumstances. She takes her support role seriously, as she – more than most, due to her career in nursing – understands its importance to patients; her sister, in this case. Cindy, as a result, comes across as laid back and has an energetic spring in her step.

Despite having left early as they always do, the heavy fog and wet morning meant road conditions were heavier than usual. But nothing was going to get in their way…

Cindy is part of a clinical trial, or research study, that is testing an investigative drug therapy for the prevention of Alzheimer’s disease. It is one of many dementia research trials from the Brain Lab in the Dr. Sandra Black Centre for Brain Resilience and Recovery at Sunnybrook Health Sciences Centre.

A volunteer participant for the study, Cindy is required to come in to hospital for regular visits – twice a month in her case, for now. This trip marked a year of visits; expected to continue another four years, for the duration of the five-year study.

Why would someone like Cindy – who shows no symptoms of Alzheimer’s disease – need or want to take that time to participate in such a research study?

When I first heard about this study, I knew right away I wanted to be a part of it. My mother had dementia, Alzheimer’s disease (AD). Seeing mom deteriorate mentally, it was difficult. She would have been in her late sixties, when she started manifesting confusion. She deteriorated; it was tough to see her go downhill. I wanted to learn what my risk was, to see if I could get more information, and what I could do about it”

Cindy Greatex,
clinical trial research participant,
68 years old 

Dementia is a term for several diseases that affect memory, thinking, and the ability to perform daily activities, with Alzheimer’s being the most common, contributing to about 60 to 70 per cent of dementia cases.

According to the World Health Organization, the illness gets worse over time and mainly affects older people. Having a family history of Alzheimer’s disease – in particular, if a biological parent or sibling has the disease – increases the risk of developing it.

As a part of the study, Cindy had the option to have her genes tested; she didn’t hesitate. The results showed that she has the strongest genetic risk factor for AD – which means she has a 15 times higher risk of developing the brain disorder than the average person.

As a medical doctor, Sunnybrook cognitive neurologist and brain scientist Dr. Sandra Black knows too well the devastating effects that diseases of the brain can have on patients, their quality and length of life, and their impact to families and loved ones.

Recognized internationally for her contributions to the diagnosis and treatment of vascular dementia, Alzheimer’s disease and stroke, Dr. Black has been compassionately providing care to patients and their families for most of her career, while working to advance research into what we know about the brain. This includes leading 88 clinical trials and training 110 trainees – new generations of clinicians and brain scientists, who have gone on to be leaders in cognition, stroke and dementia across the country.

While there are drug therapies available to help treat some of the symptoms of AD or other dementias (once those symptoms have already developed), there are limited medical options to address prevention, before the disease takes hold.

Yet Dr. Black has never been more optimistic.

Never before did we have the option or possibility of altering the pathway in which dementia develops. Now we’re actually looking at the pathology itself that leads to brain cell damage and cognitive decline. This is an emerging field and we’ve learned the sweet spot in preventing or slowing down Alzheimer’s disease is well before symptoms start.

Sandra Black,
Scientific Director, Dr. Sandra Black Centre for Brain Resilience and Recovery,
Sunnybrook Research Institute (SRI) and
Officer of the Order of Canada

She explains how the focus of therapies in their clinical trial research now is to intervene before the toxic processes behind the disease begin to form – a minimum of 10 to 15 years before symptoms kick in and “have a life of their own”, spreading in the brain.

“If we can do that, then you’re going to avoid it (dementia developing). It’s like stroke prevention: you get worked up, and put on prevention therapies, so you don’t have a stroke.”

The comparison should not go unnoticed, considering that she and her colleagues at Sunnybrook’s stroke clinic were one of the first to provide stroke prevention therapies in Canada in the 1990’s.

For the time being, volunteering to participate in a clinical trial is often the best option for patients like Cindy to access therapies that are not yet available “clinically”; in this case, a drug therapy in an effort to prevent or offset the very start of the disease process.

Receiving the drug, however, is not a guarantee as clinical trials are often randomized and blinded, which means volunteer participants are either selected for the drug therapy itself, or a “placebo” instead – the latter usually is just a saline solution – so Cindy and the research team don’t know which group she falls in.

“There has to be this placebo comparison in order for the study to be controlled, in order to validly test for any effects and differences – good or bad – of a drug being studied,” explains Halil Akbulut, clinical research coordinator in the Hurvitz Brain Sciences Program at Sunnybrook.

Without people like Cindy and her study support partner, we wouldn’t make any progress at all. They’re contributing to our understanding.

Cindy will continue to be closely monitored and tested for the duration of the study. Her sister Debbie is her “study partner”. In addition to providing a supportive role to Cindy, Debbie is part of her “team”, sharing any cognitive, physical or emotional changes she observes while outside the hospital setting. Changes to cognition can include thinking processes such as attention, learning and memory, language, remembering, reasoning, and problem solving.

If Cindy’s cognition or overall health declines, she will be pulled from the study. If it’s found that she was on the placebo, she will be offered the drug therapy as part of the agreement as a participant of the study. If she was on the drug arm of the study, she will continue to be offered it, for as long as she and her care team decide to use it.

I’m learning so much through this study, I’m learning how to eat better, how to sleep better, interacting more with people; so it’s giving me a lot of tools that I can put into place now while I’m going through the study, and I know it will make a difference in my life, to a better quality of life.

When asked if she had any advice to offer others who may be considering a clinical trial, Cindy added:

“If there are clinical studies available, sign up. It helps to find out as well genetically whether you have a predisposition – a higher probability of getting the disease – so there’s so many good points about being part of a study. I encourage people to find out if anything is happening in your community – I’m commuting myself – it’s worth the while to do that.”

The post Igniting Discovery: Can we stop dementia in its tracks, before it starts? appeared first on Your Health Matters.

With no cure for the disease, scientists around the world are conducting research that is leading to breakthroughs in the diagnosis, progression and prevention of Alzheimer’s. Dr. Julie Ottoy, scientist in the Hurvitz Brain Sciences Program, is one of the many researchers at Sunnybrook Research Institute, studying the pathophysiology of Alzheimer’s and what impacts it has on patient outcomes.

Dr. Ottoy’s interest in researching the causes and progression of Alzheimer’s disease started from her personal experiences. Like many Canadians, she has seen firsthand how the disease can impact the lives of family members and friends. Her experiences with her own loved ones and conversations with individuals with lived experience have played a pivotal part in shaping her work.

They remind me time and again that the research we do is about people, their families and their futures.

Dr. Ottoy’s research is working to answer some of the most fundamental questions surrounding Alzheimer’s. Who is most likely to develop Alzheimer’s? In what cases does the disease progress faster? Can we detect changes in the brain before symptoms appear?

Her work specifically focuses on better understanding mixed dementia. This is when Alzheimer’s disease occurs alongside vascular brain damage, which occurs when the blood vessels in our brain are affected and the blood flow to the brain is disrupted. Although mixed dementia is common, it’s not fully understood, making diagnosis and treatment challenging.

Using advanced neuroimaging techniques, like PET and MRI scans, blood-based biological markers, computational biology and AI-based analysis tools, Dr. Ottoy’s research focuses on two overarching themes:

• Mechanisms: To better understand how changes in our blood vessels and immune system contribute to brain changes seen in Alzheimer’s and mixed dementia.
• Biomarkers: To investigate novel biological markers that can aid researchers and clinicians in predicting the progression of these disorders in their early stages.

Her research looks for signs of vascular damage on brain scans, patterns of inflammation and the presence of toxic proteins that form into amyloid plaques and tau tangles. By combining this information, researchers can group patients into more specific subgroups based on the biological changes driving their disease, in turn driving more targeted intervention.

Photo illustration. Kevin Van Paassen/Sunnybrook Health Sciences Centre.

“Alzheimer’s is a very heterogeneous disease, meaning there is a number of different contributing factors and causes for the disease,” explains Dr. Ottoy. “By identifying different subgroups of patients using biomarkers, we are a step closer to creating more tailored treatments that match the individual needs of each patient more closely.”

Another area of her research investigates how well different brain regions connect with one another. The abnormal buildup of tau, one of the toxic proteins in Alzheimer’s disease, leads to cognitive decline in Alzheimer’s disease. Some studies suggest the way brain regions connect with each other is a key mechanism for the spreading of tau. Dr. Ottoy’s work studies these highly-connected regions and tau epicentres, to predict where the tau will build up next.

By studying the interface between the vascular system, immune cells and the spread of Alzheimer’s-specific toxic proteins throughout the brain, scientists can identify novel treatment targets, determine the best time and approach for disease intervention and develop new biomarkers that can inform future clinical trials and potential treatments. Understanding immuno-vascular contributions to dementia is important because both vascular and immune factors are modifiable.

With the advent of disease-modifying treatments, we are closer than ever in meaningfully slowing the progression of Alzheimer’s disease.

Today’s research lays the groundwork for larger-scale initiatives, including multi-site collaborations, like Toronto’s first 7-Tesla MRI, housed at Sunnybrook and part of the Toronto Neuro-Immunology/Imaging Consortium (TONIIC), a multi-site collaborative research initiative focused on neuroimmunology and neuroimaging for diseases such as Alzheimer’s. These research efforts will deepen understanding of disease mechanisms and aid in identifying new biomarkers and therapies.

“My hope is that these advancements will drive the development of combination treatment strategies that reach the clinic and accelerate progress toward precision medicine for neurodegenerative diseases.”

Dr. Ottoy’s research in immune-vascular contributions to dementia is funded by the Alzheimer’s Association and BrightFocus.

The post Understanding the causes and progression of Alzheimer’s disease: Scientist spotlight on Dr. Julie Ottoy appeared first on Your Health Matters.

Alzheimer’s disease is a brain disorder that affects memory and behaviour and interferes with everyday life. As the disease progresses, individuals experience more cognitive difficulties, and can lose their ability to read, walk or recognize loved ones. Some risk factors include age, genetics and sex, however anyone can get it in their lifetime. People with dementia have different experiences, but the effects of the disease are felt by many – patients, family members and friends alike.

While there is currently no cure for Alzheimer’s disease, efforts are being made worldwide to manage the disease. At Sunnybrook, scientists are driving the innovation and treatment of brain health and creating hope for the future.

Improving diagnosis and treatment

Much of the international criteria we have now for Alzheimer’s disease and other dementias is thanks in part to contributions from The Sunnybrook Dementia Study, a 25-year observational study measuring and monitoring changes in patients with dementias, vascular disease and other neurodegenerative diseases. Led by Dr. Sandra Black, cognitive neurologist and senior scientist at Sunnybrook, this study began in 1995 and is applying advanced MRI, genetic testing and cognitive and functional assessments at yearly intervals to measure and monitor changes in patients with neurodegenerative diseases.

The study has been a success thanks to its multidisciplinary team and importantly, the more than 1600 patient participants explains Dr. Black. “We learn from our patients, engage them in a partnership — it’s research embedded in care.”

Some of these patients may go on to participate in one of the many Alzheimer’s clinical trials at Sunnybrook. There are currently participants in several pharmaceutical studies that are working toward potentially modifying the disease by testing antibody therapies that can remove amyloid plaques in the brain. One example is the AHEAD study, which is exploring whether an investigational treatment can slow or stop the earliest brain changes due to Alzheimer’s disease. Researchers can detect changes in the brain of those with Alzheimer’s disease up to 20 years before symptoms begin. The goal of the AHEAD study is to prevent the development of memory loss and other symptoms, before the plaques cause too much damage to the brain.

While not yet approved in Canada, researchers and clinicians are also excited about new blood tests, available through research trials, that are being used for screening those at higher risk of developing Alzheimer’s disease. In addition to this screening process, amyloid PET scans are done using Sunnybrook’s Cyclotron facility, Health Canada’s only approved tracer for detecting amyloid deposits in the brain.

“Thanks to rapidly advancing precision medicine technologies, Alzheimer’s disease may soon become a preventable and treatable condition,” says Dr. Black. “This is a very exciting time in research, given the increasing prevalence of Alzheimer’s disease in Canada’s aging population.”

Addressing changing dementia demographics

In the past 20 years, Canada’s population has changed, but much of our scientific understanding of dementia risk factors is based on populations of European descent. As the population profile of dementia patients is projected to change, more research is needed to address the unique needs and experiences of diverse communities. The Canadian Multi-Ethnic Research on Aging (CAMERA) study aims to understand the risk factors of Alzheimer’s disease in diverse ethnic groups in Canada.

The study, led by Dr. Jenny Rabin, scientist in the Hurvitz Brain Sciences Research Program at Sunnybrook Research Institute, is following 300 participants, free from significant cognitive impairment, across three different ethnic groups: individuals from European, South Asian and Chinese descent. The study will allow researchers to study the earliest changes associated with Alzheimer’s disease and other cognitive disorders. CAMERA is the first study in Canada that brings together brain imaging and cognitive measures to investigate risk factors for dementia in a multi-ethnic cohort.

“This knowledge will ultimately allow us to develop more effective dementia prevention and intervention strategies for Canada’s diverse communities,” says Dr. Rabin.

Changing the course of the disease

The biggest risk factor for Alzheimer’s disease is age. Most individuals diagnosed with dementia are over the age of 65, however about one per cent of people with Alzheimer’s will have the genetic form known formally as autosomal dominant Alzheimer’s disease (ADAD). Also referred to as early-onset familial Alzheimer’s disease, the condition is genetically inherited or passed down through families. Individuals will begin to experience cognitive decline as early as their 30s. In Canada, there are more than 25,000 people under the age of 65 living with dementia.

“In the prime of your life, you’ll begin to experience memory loss, then develop changes in behaviour, such as trouble controlling emotions. You may lose your inhibitions. Eventually, you will lose the ability to communicate,” says Dr. Mario Masellis, neurologist and associate scientist at Sunnybrook.

In Alzheimer’s diagnosis and treatment, time is of the essence – the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) drug trial, is working toward slowing down, even potentially stopping, dementia symptoms in those predisposed to the Alzheimer’s gene. Dr. Masellis is leading the trial at Sunnybrook, one of the few Canadian sites taking part in the global study. The trial is testing two drugs that aim to lower the levels of the substance that causes amyloid plaques in the brain, which play a central role in Alzheimer’s disease.

Because early-onset dementia makes up a small number of dementia cases, there are fewer support systems for those patients, who may begin to experience cognitive decline while they’re still raising a family or growing their career. Research from the DIAN-TU trial can lead to the development of early intervention and prevention therapies to help people with early-onset Alzheimer’s disease.

The Garry Hurvitz Brain Sciences Centre

Sunnybrook’s new Garry Hurvitz Brain Sciences Centre, currently under construction, is a collaborative, state-of-the-art facility that will bring together clinical and research spaces to continue to advance Alzheimer’s diagnosis and care.

There may not be a cure yet, but the future of Alzheimer’s treatment is promising, thanks to the work of dedicated scientists and healthcare professionals at Sunnybrook and around the world.

The post How Sunnybrook is creating hope for patients living with Alzheimer’s disease appeared first on Your Health Matters.

In the early stages of these devastating diseases, symptoms may be subtle. Individuals may be more forgetful than usual or have trouble learning new things.

As their disease progresses, they experience greater cognitive difficulties and memory loss. They may lose their ability to find their way home, to pay bills, to read, write or complete everyday tasks. They may exhibit confusion, erratic behaviour and personality changes. Eventually, they may no longer recognize their loved ones.

This loss of cognitive functioning is a reality for the estimated 600,000 Canadians living with Alzheimer’s disease and other dementias. Since age is a leading risk factor and our population is aging, that number is expected to climb to more than 1.7 million by 2050, meaning there is a growing and urgent need for therapeutic options.

Having witnessed the ravages of these diseases in countless patients, renowned Canadian neurologist Dr. Sandra Black now sees a light at the end of the tunnel.

In fact, it’s an exciting time to be working in the field, she says.

“We could be entering a whole new era,” says Dr. Black, senior scientist and director of The Dr. Sandra Black Centre for Brain Resilience and Recovery at Sunnybrook Research Institute.

“We may be very close to having some treatments for Alzheimer’s disease that would be disease-modifying,” she says. “I hope we’re going to be in a similar situation as what happened in acute stroke, which has been transformed into a treatable condition if caught early enough and is often preventable if risk factors are managed.”

During her nearly 40-year career, Dr. Black has been at the forefront of advances in understanding and treating stroke, Alzheimer’s disease and other neurodegenerative diseases. One of the country’s most accomplished scientists, Dr. Black has received numerous awards for her work, including being appointed as an Officer to the Order of Canada and the Order of Ontario.

With more than 600 publications to her name, Dr. Black is renowned clinically and scientifically in Canada and is an influential leader and collaborator in international initiatives.

As the inaugural scientific director of the Dr. Sandra Black Centre for Brain Resilience and Recovery at Sunnybrook Research Institute, Dr. Black leads some of the top minds in stroke, Alzheimer’s and dementia research. Now, as life-changing therapies for these pernicious disorders are becoming available, the leading-edge work she and her colleagues are doing is especially important.

A life-long desire to help others

Dr. Black helped usher in the modern era of stroke care. During her training, stroke was still a “dead-end” disease, she says. But in the 1990s, as the first woman to head a division of neurology in Canada, she made sure that Sunnybrook was among the first Canadian hospitals to implement the revolutionary clot-busting medication tPA.

“Gradually, the need to treat early led to important system changes in Ontario and other provinces and a whole new way to change the future of stroke,” she says.

Recognized as one of the world’s leading experts on dementia and Alzheimer’s disease, Dr. Black hopes to see the same progress happen in dementia prevention and treatment.

“As we get into what I think is going to be a transformative period in our field, my dream is that we will have treatments for Alzheimer’s disease that are disease-modifying and meaningfully slow disease progression,” she says. “We are very close to that now with a number of promising ongoing clinical trials.”

Dr. Black inherited her desire to help others while growing up in Sault Ste. Marie, Ont. Her father was a physician. Her mother, who was a community activist supporting social services and promoting music and the arts, was appointed a member of the Order of Canada in 1985. Dr. Black and her three siblings (two physicians and a choral director and teacher) are similarly motivated, she says. “Our parents modelled duty of care.”

In fact, Dr. Black’s prestigious research career grew out of her work as a physician caring for people with stroke, Alzheimer’s, Parkinson’s and other degenerative nervous system diseases.

“I do what’s called research embedded in care, [which means] learning from patients by studying them as consenting partners and correlating behavioural patterns with changes in the brain seen on imaging, now enhanced by advances in genetics and blood biomarkers,” she says.

This concept was the genesis of the landmark Sunnybrook Dementia Study of more than 1600 patients, which contributed to developing international consensus criteria for Alzheimer’s and several different types of dementia. This study has proven to be valuable to other researchers in the field, generating and contributing to more than 190 peer-reviewed publications in highly regarded international journals.

As a teacher and mentor, Dr. Black has also nurtured the talents of dozens of scientists and researchers. Her prowess in this area has earned outstanding mentorship awards from U of T’s Institute of Medical Sciences and department of medicine.

Dr. Jennifer Rabin

Dr. Jennifer Rabin, a neuropsychologist and scientist in the Harquail Centre for Neuromodulation and also the Dr. Sandra Black Centre for Brain Resilience and Recovery in Sunnybrook’s Hurvitz Brain Sciences Research Program, says she returned to Toronto from Harvard Medical School in part “because it’s the home of Dr. Sandra Black.”

Dr. Rabin credits her colleague with helping guide her through the complicated process of setting up her own research program, where she is currently studying dementia risk factors in people of South and East Asian origin. Dr. Black is “a luminary in the field, and also the warmest and nicest person you will ever meet,” says Dr. Rabin. “No matter how busy she is, she will always find the time for you.”

Dr. Maged Goubran

Dr. Maged Goubran is a Sunnybrook scientist who specializes in medical biophysics, computational neuroscience and artificial intelligence (AI). Since joining Dr. Black’s lab as a research associate from Stanford University, he has become one of her close collaborators, applying machine learning techniques to quantify magnetic brain imaging data in correlation with cognitive deficits and outcomes. These AI models are “trained” using patient data meticulously collected and processed as part of the Sunnybrook Dementia Study and can give key regional brain measures in a matter of minutes.

“I don’t think I’ve ever worked with anyone who has the same level of dedication, genuine care and support for her trainees and patients,” says Dr. Goubran. “It’s so inspiring.”

A new hub for multidisciplinary expertise

As a lifelong proponent of collaboration and cooperation, Dr. Black has high hopes for what will be accomplished at Sunnybrook’s under-construction Garry Hurvitz Brain Sciences Centre, a state-of-the-art facility for patient care and research that is quite unique in Canada.

In bringing together experts across disciplines – from Alzheimer’s disease, ALS, dementia and stroke to mental health and mood disorders – the Garry Hurvitz Brain Sciences Centre will be well positioned to develop the next generation of novel treatments, she says. “By housing our clinics and some research space together in one building, it will allow us to interact more often and more closely.”

Dr. Black points out that “none of this would have been possible without philanthropy.” While the active industry-sponsored trials cover their costs, donations are needed to help support the teams needed for numerous investigator-driven studies that are typically underfunded.

“For example, philanthropic donation to our cognitive neurology unit allowed us to accelerate the development of our very unique, personalized brain imaging pipeline,” she adds.

With so many promising developments happening at Sunnybrook in the field of dementia research right now, philanthropy is more crucial than ever, says Dr. Black. She’s encouraged by the generosity of those who are supporting the Garry Hurvitz Brain Sciences Centre and the work she and her team are doing at the Dr. Sandra Black Centre for Brain Resilience and Recovery.

It’s the kind of work that could be life-changing for thousands of Canadians in the years to come.

“I think donors [appreciate] the optimism I have about the future,” she says. “I’m still very active, and we’ve attracted some brilliant young leaders in the fields of stroke and cognitive and movement disorders, some early and mid-career and others still in training, poised to become very talented, next-generation clinicians and research scholars.”

To learn more on how you can support Sunnybrook’s Garry Hurvitz Brain Sciences Centre and help invent the future of brain health, visit Sunnybrook.ca/brain

The post ‘A whole new era:’ Why we may be getting closer to treatments for Alzheimer’s disease and other dementias appeared first on Your Health Matters.

“You can’t deal with it by denying it,” says Ron. “It’s important to get real about what’s happening. If you’ve fallen and broken your wrist, you’re not afraid to get help. It is a bit like that. Get real, get help and get ready. Find out how your life is going to evolve. Be prepared, not scared.”

Through his involvement with the Alzheimer’s Society, Ron was introduced to the Driving and Dementia Roadmap (DDR), a free online resource that was developed by researchers at Baycrest, Sunnybrook and the Canadian Consortium on Neurodegeneration in Aging (CCNA). Its goal is to empower older adults living with dementia to make informed decisions about when to stop driving.

Ron and his wife, Sandy, were watching one of the video resources about driving, dementia and safety in the community from the DDR website in preparation for a workshop, and that video helped Ron come to a decision.

“I decided right then and there that I was going to stop driving,” he says.

While the decision was swift, it was not insignificant. Ron says he has always loved driving, describing himself as a very active driver who first learned by driving farm equipment when he was young.

“I competed in rally driving early in my 20s; I was an airplane pilot. Driving has always been a large part of my life,” Ron says, adding driving has been part of his and Sandy’s relationship and experiences together as well: they’ve driven across the country several times, and all through Europe.

But Ron has known, since he was diagnosed with dementia, that he was going to have to stop driving eventually.

“To me, it has always been a question of when am I going to stop, not if,” he says. So, when he and Sandy were watching one of the DDR resource videos on how dementia can impact one’s driving and how the risks will inevitably increase, it resonated strongly.

“I decided to stop driving because I couldn’t stand the risk of possibly being responsible for hurting somebody when I was driving,” he says.

Planning Ahead

Doctors say driving is about much more than getting from point “A” to point “B.”

“Driving gives an individual a sense of identity,” says Dr. Mark Rapoport, geriatric psychiatrist, acting head of Geriatric Psychiatry at Sunnybrook and one of the researchers behind the DDR website. “Driving helps a person be more independent, enables them to be a part of social circles, and go to activities they enjoy.”

Dr. Rapoport says the DDR provides strategies that can help individuals and their families plan ahead.

“It may be that a person gets around with the help of family, friends, rideshare, or various transportation support services,” says Dr. Rapoport. “We want people to keep living their best lives, even after they stop driving.”

Ron says one thing that, for him, has made the decision more manageable is that Sandy drives, and he has several friends who live nearby and can drive him places as well. Sandy says it’s required some adjustment to their schedule, but overall, it’s been a smooth transition.

“We had to start thinking, whenever we scheduled things, one driver. Our scheduling has changed considerably — booking appointments so both of us go at the same time, or doing the groceries together instead of Ron doing them alone,” she says. “It’s working out quite well, though. Nothing to worry about, just small changes.”

Dr. Rapoport adds that: “The DDR encourages people with dementia and their families to have a more robust transportation plan that avoids having all the driving taken over by one family member.”

Sandy says she found the DDR resources for family members and loved ones of individuals with dementia an accurate reflection of what individuals and families are going through during this decision to stop driving.

“There are excellent suggestions in the videos for how people can approach this conversation about driving with a loved one who has dementia,” she says. “How a friend can do it, how an adult daughter can do it. And all the frustration that the person with dementia can experience as part of the process — I think that’s good for anyone in the family to see.”

The DDR has also been recognized by the World Health Organization (WHO) as a dementia resource on the WHO’s Global Dementia Observatory Knowledge Exchange Platform.

“Among many other topics, the Driving and Dementia Roadmap helps users understand how dementia can impact driving; identify when it becomes unsafe for individuals living with dementia to drive; deal with the emotional aspects of driving cessation; and adjust to life without driving once the decision has been made,” says Dr. Gary Naglie, geriatrician, researcher and Vice-President, Medical Services & Chief of Staff at Baycrest.

Dr. Mark Rapoport says this resource meets a need for patients and families that wasn’t there before.

“In my work in the field of geriatric psychiatry, over time I found that patients and families identified the need for easily accessible and credible information about driving and dementia and driving cessation,” he says, adding the DDR is the first time helpful materials have been curated into a one-stop-shop website that includes resources useful for all provinces and territories in Canada.

Making the decision to stop driving

“Driving is part of my identity, not just in terms of my independence, which is very important, but also, I’ve always thought of myself as a good driver,” says Ron. “I’ve enjoyed driving and it did become part of who I am. That’s a huge issue for me, and for other people.”

When he thinks of advice that he would offer about how to make the decision to stop driving, he says there isn’t an easy answer, but he does say individuals with dementia need to acknowledge that it’s “when, not if” they will have to stop driving.

Ron says part of what makes the DDR website such a “phenomenal resource” is that it’s helping people understand and make personal choices about their own driving ability in a way that’s non-threatening and supportive.

And he says, in addition to the DDR website, the Alzheimer’s Society of Canada provides excellent support for people with dementia as they navigate their diagnosis. 

Where to find more information on the DDR website resource

People with dementia, as well as family members or other loved ones, can access the resources available on the DDR website for free, but should also be in contact with their healthcare provider for guidance, advice and support in making the decision about driving and their overall dementia journey, as the website is for educational and informational purposes.

Ron and Sandy are grateful to the team of researchers who created the resource and helped them come to the decision that it was time for Ron to stop driving.

The Posnos add they continue to enjoy life and their daily activities. Ron says, they simply plan ahead.

“What we do now is focused on what we can do.”

To learn more about the DDR website resource: drivinganddementia.ca

Read: Driving and dementia: How to know when it’s time to stop driving

The post How the Driving & Dementia Roadmap helped Ron make an important decision appeared first on Your Health Matters.

In a recently published preclinical study, Dr. Isabelle Aubert, senior scientist at Sunnybrook Research Institute and postdoctoral researcher Dr. Kristiana Xhima successfully used focused ultrasound to non-invasively deliver a therapeutic in the brain, targeting brain cells affected by Alzheimer’s disease and improving cognition.

The study has been published in the journal BRAIN.

This is the first study to demonstrate that repeated focused ultrasound blood-brain barrier modulation in the basal forebrain is safe in the presence of Alzheimer’s pathology, and when combined with a growth factor-related therapeutic, can lead to therapeutic effects. Focused ultrasound harnesses the power of sound waves to transiently open the blood-brain barrier, a protective barrier that prevents toxins or potentially helpful therapeutics in the bloodstream from entering the brain.

This promising research comes at an urgent time. It is estimated that more than 600,000 Canadians are currently living with dementia. According to a recent report from the Alzheimer’s Society of Canada, rates of dementia, including Alzheimer’s disease, are projected to rise to nearly 1 million people in Canada by 2030. Below, Drs. Aubert and Xhima discuss how their breakthrough research is an important advancement on the road to developing effective therapeutic approaches for the disease.

Dr. Aubert and Dr. Xhima

What was the impetus behind your study?

Dr. Aubert: This preclinical study was a follow-up to our previous proof-of-concept study that used MRI-guided focused ultrasound to non-invasively deliver a type of growth factor-related therapeutic (D3) to brain cells called cholinergic neurons, which are important for learning and memory and most vulnerable in Alzheimer’s disease. D3 stimulates important signaling mechanisms in brain cells that are related to the tropomyosin receptor kinase A (TrkA) pathway. The TrkA pathway is critical for neuroprotection, plasticity and survival of cholinergic neurons; engaging it with D3 promotes the resilience of brain cells against Alzheimer’s pathology.

In our first proof-of-concept study, we had found that D3 combined with focused ultrasound efficiently stimulated key survival and neuroprotective pathways, and in the short-term, helped to restore brain cell communication (also known as neurotransmission). Yet for clinical translation and impact, it was critical for us to study whether focused ultrasound combined with D3 could rescue cognitive function – the rationale and goal of the current study.

What did your current study find?

Dr. Xhima: In this preclinical study, we demonstrated the therapeutic potential of D3 in a preclinical model of Alzheimer’s and showed its impact on learning, memory and cognitive flexibility. The D3 therapeutic agent, like many promising therapeutics, does not have the properties required to efficiently cross the blood-brain barrier (BBB) and reach its targets deep in the brain. To overcome this challenge, we coupled the intravenous administration of the therapeutic drug D3 with MR-guided focused ultrasound to non-invasively, locally and transiently increase BBB permeability in key brain regions for the effective delivery of D3 from the blood to the brain.

Following brain delivery of the therapeutic agent with focused ultrasound, performance in cognitive tasks was improved. The treatment of focused ultrasound with the therapeutic D3 led to enhanced neurotransmission in cholinergic neurons, which are highly vulnerable to injury in Alzheimer’s disease. We also observed beneficial effects on brain regeneration – new brain cells were formed in the hippocampus, an area of the brain that plays a major role in learning and memory, and amyloid plaques, common in Alzheimer’s, were reduced in targeted brain areas.

What could these results mean for patients and clinicians in the future?

Dr. Aubert: Although still early-stage, this work is an important and fundamental step in the development of potential treatments for the disease. The results also open the door for many other regenerative agents, that normally do not cross the BBB, to be tested and delivered using this drug-delivery platform. This is the first study to demonstrate that a growth-factor related agent delivered to the basal forebrain and associated cortical and hippocampal areas repeatedly using focused ultrasound BBB modulation is safe and can lead to therapeutic effects in the presence of Alzheimer’s pathology. These results provide a major step forward in terms of drug delivery that can be very promising for clinical translation.

Dr. Xhima: Another key feature of this preclinical research is that we tested focused ultrasound delivery of a TrkA-stimulating agent in the presence of established Alzheimer’s pathology. In contrast to many previous studies, here we showed that this therapeutic approach rescued cognition and improved Alzheimer’s related pathologies once they were already established, similar to how patients would present in the clinic. The beneficial effects of the treatment were also broad with respect to several key systems affected in Alzheimer’s disease. This makes us very hopeful about this therapeutic approach because it certainly represents an important step forward for potential clinical development.

What’s the next step in this work?

Dr. Xhima: The improvements in cognitive function we saw in the preclinical models studied lasted for several weeks, which raises the question: how often will treatment need to be repeated for therapeutic effects that can last over months and years?

Dr. Aubert: In addition to this, we’re interested in taking an exploratory approach to look at other molecular pathways in the brain that could also be affected by this treatment, since our results went beyond what was expected with target engagement on cholinergic neurons alone.

It’s important to note that this research is still at an early stage and has not yet moved to clinical trials. We are hopeful that this fundamental research will translate into the clinic in the near future, as we continue to explore therapeutic options to stop degeneration and promote regeneration in Alzheimer’s disease and dementia.

Hear Dr. Aubert and Dr. Xhima discuss their findings in further scientific detail on the BRAIN podcast, the official podcast of Brain and Brain Communications.

The post Behind the research: New study finds focused ultrasound enhances delivery of brain therapeutic and improves cognition in Alzheimer’s appeared first on Your Health Matters.

Despite the statistics, innovative research is underway at Sunnybrook to help bring hope to the fight against Alzheimer’s and dementia.

“We may be entering a new era with possible effective treatments for this disorder which affects whole families and is increasingly prevalent with populations aging,” says Dr. Sandra Black, director of the Dr. Sandra Black Centre for Brain Resilience and Recovery. “Continued research is critical as we aim to develop and discover meaningful treatments and prevention strategies for Alzheimer’s and dementia.”

Here are just some of the innovative ways that Sunnybrook clinicians and researchers are on the leading edge of research in the detection, prevention, and treatment of Alzheimer’s and dementia.

Apathy and Agitation in Alzheimer’s

At Sunnybrook, clinical studies are underway on apathy and agitation in Alzheimer’s patients, where researchers are exploring ways to help decrease apathy in patients. This can help increase their interest in activities and their emotional responsiveness, which may help improve their quality of life, as well as their caregivers’.

Early on-set dementia

In a world-first study, a team of Sunnybrook scientists are trying to identify biomarkers, or biological clues in the brain, such as blood flow, that could demonstrate an early-onset frontotemporal dementia in people who have a genetic predisposition to the disease.

 

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Innovative technology

Researchers are also looking for innovative ways to deliver medicine or therapeutics directly to the areas of the brain involved in Alzheimer’s disease.

Preclinical research is exploring the delivery of gene therapy to treat Alzheimer’s and help improve memory and boost brain health.

One of those methods uses focused ultrasound technology, where ultrasound waves are precisely directed to a targeted area of the brain to help open the blood-brain barrier (BBB), which can allow potentially helpful medications to reach brain regions involved in Alzheimer’s and dementia, without having to use scalpels. Research teams have shown evidence that the BBB can be temporarily opened safely using focused ultrasound, an exciting first step in exploring a new way for therapeutics to be delivered to the brain.

Who will get Alzheimer’s disease?

Sunnybrook scientists are also using artificial intelligence and machine learning to try and detect early signs and symptoms of dementia to improve treatment and prevention of the disease.

Research is also underway to learn more about risk factors for dementia among diverse ethnic groups including individuals of South Asian and Chinese descent, as these groups are often under-represented in dementia studies.

The latest Sunnybrook research has also demonstrated that having poor vascular health may accelerate cognitive decline in patients with dementia and small vessel disease.

Preventing Alzheimer’s

Researchers are finding out how lifestyle can protect individuals from dementia.

While it is critical for cutting edge studies to continue in the search for new treatment and care for patients with Alzheimer’s and dementia, it can also be helpful for individuals to take action themselves to learn more about dementia and how activity can help boost brain health in more ways than one.

From prevention to diagnostics and potential treatment innovations, “We’re at the forefront of discovery for dementia and Alzheimer’s at Sunnybrook,” says Dr. Black. “There’s a lot to be optimistic about.”

The post Advancing Alzheimer’s research appeared first on Your Health Matters.

“The main theme of both studies is that people who have both Alzheimer’s disease and poor vascular health decline much more quickly than people who have only one of these conditions,” says Dr. Rabin, a scientist at SRI in the Hurvitz Brain Sciences Program.

There is growing evidence that vascular health and Alzheimer’s disease are closely intertwined, and that poor vascular health may promote the build-up of amyloid and tau in the brain, the two abnormal proteins associated with Alzheimer’s disease. “Preventing vascular disease may also help to prevent Alzheimer’s disease,” says Dr. Rabin.

The findings of the first study were published in Brain and the results of the second study were published in Neurology. Both are highly prestigious journals. Dr. Rabin, who was the only Canadian researcher involved in the studies, collaborated with U.S. colleagues to conduct the research.

Scientist Dr. Jennifer Rabin

What did you learn about the connection between CAA and Alzheimer’s disease?

The Brain study looked at a cerebrovascular condition known as cerebral amyloid angiopathy (CAA), which results from the build-up of amyloid in the blood vessel walls of the brain. When there is accumulating amyloid in the vessel walls it can cause vascular brain changes, such as small hemorrhages and blood flow problems. Although amyloid plays a central role in both CAA and Alzheimer’s disease, the two conditions are considered distinct.

The study is titled, “Cerebral amyloid angiopathy interacts with neuritic amyloid plaques to promote tau and cognitive decline.”

Dr. Rabin and colleagues from multiple U.S. centres asked the question: What influence does CAA have on the build-up of tau (the more detrimental hallmark pathology of Alzheimer’s disease) and cognitive decline, either alone or in combination with amyloid burden?

They analysed data from 1,722 autopsied subjects recruited from one of three long-running medical studies. Data included annual clinical and cognitive evaluations, along with neuropathology. The researchers tested associations between CAA, tau burden and cognitive decline, both independently and together with amyloid burden.

They found that the combination of CAA and higher amyloid levels were associated with the greatest tau burden and the fastest rates of cognitive decline.

“Not everyone with CAA has Alzheimer’s disease and not everyone with Alzheimer’s disease has CAA. But they do co-occur at a high rate,” says Dr. Rabin. “We found that if you have both of these conditions, you were much more likely to have tau burden and faster cognitive decline.”

How do classic vascular risk factors affect the brain?

The study in Neurology looked at whether classic vascular risk factors, such as obesity, high blood pressure, smoking and diabetes, leads to faster brain tissue loss and faster cognitive decline when they co-occur with amyloid.

The study is titled “Association of β-Amyloid and Vascular Risk on Longitudinal Patterns of Brain Atrophy.”

Dr. Rabin and colleagues from Massachusetts General Hospital analysed clinical and neuroimaging data from 196 subjects in the Harvard Aging Brain Study, a long-standing, community-based study.

They found that people who had multiple vascular risk factors and high levels of amyloid had greater rates of brain tissue loss and cognitive decline over time. “The take away,” says Dr. Rabin, “is that managing vascular risk factors may slow the progression of Alzheimer’s disease dementia.” This includes controlling blood pressure, lowering cholesterol, maintaining a healthy weight, and refraining from smoking. A good rule of thumb is that what’s good for the heart is good for the brain.

What do these results mean for patients and care providers?

These two studies provide greater support for the idea that vascular health and Alzheimer’s disease interact in ways that increase the likelihood of a dementia diagnosis. “These findings have implications for developing treatments for Alzheimer’s disease,” says Dr. Rabin, “because they suggest that vascular health should be taken into account. Treatments that target poor vascular health and Alzheimer’s pathology are likely to be the most effective.”

How you can get involved

If you are interested in getting involved in Dr. Rabin’s research studies, please send an email to cbhlab@sunnybrook.ca.

The post Behind the research: Studies provide more evidence that poor vascular health speeds up cognitive decline in Alzheimer’s disease appeared first on Your Health Matters.

By developing advanced machine learning and artificial intelligence (AI) models and applying them to some of the largest data sets in the world, Dr. Goubran’s team is learning to detect, with greater precision than ever before, cognitive decline years before symptoms arise. Also at the heart of this work is discovering what minute structural and functional changes and network breakdown within the brain can be used as biomarkers, or early/accurate indicators, of neurodegenerative disorders.

“A key missing piece in neurodegeneration research are the algorithms that learn from large amounts of individual data from magnetic resonance imaging (MRI), PET scanning, genomic analysis, and demographics, combined with results from cognitive testing, that can be applied in the clinic,” says Dr. Goubran, a scientist in the physical sciences platform at SRI. “This work is of critical importance because it can provide urgently needed guidance on prevention and personalized treatment decisions.”

[mks_pullquote align=”left” width=”300″ size=”20″ bg_color=”#ffffff” txt_color=”#000000″]“This work is of critical importance because it can provide urgently needed guidance on prevention and personalized treatment decisions.”

Dr. Maged Goubran
Scientist
Sunnybrook Research Institute

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Alzheimer’s disease is one of Canada’s greatest healthcare challenges, currently having a devastating emotional and physical burden (directly or indirectly) on more than 1.1 million people. This number is expected to rise dramatically in the next 20 years. The disease has an estimated health care cost of $10.4 billion annually.

A big focus of Alzheimer’s research and care has been on preventing symptoms earlier in the progression of disease. This tactic relies on identifying healthy adults at high risk of future cognitive decline; these people may have small changes in their brains starting a few decades before the first symptoms appear. While much research has been done in this area, Dr. Goubran and his team are improving on previous approaches in several ways: by building more powerful computational models than in the past, by using larger, more robust population data sets, by focusing on individual rather than group-level predictions (to address the large patient variability) and by pinpointing Alzheimer’s progression in asymptomatic rather than only symptomatic individuals.

Tracking progression of disease

Dr. Goubran is building on earlier research that establishes shrinkage of the hippocampus as a possible early sign of dementia. The hippocampus is the brain’s centre for memory and navigation; it is often one of the first areas to be impacted by Alzheimer’s disease.

The team is developing AI algorithms to map changes in not just the volume but also the shape of the hippocampi (and its subdivisions), as well as other important structures and vascular lesions of the brain during aging. The models are informed by hundreds of brain MRIs from multiple studies including the Sunnybrook Dementia Study led by Dr. Sandra Black, senior scientist and director of the Sandra Black Centre for Brain Resilience and Recovery at SRI. The researchers will use these imaging biomarkers and a normative population of thousands of Canadians to track and predict patient progression.

Others around the world will benefit from these AI techniques, as the team will validate and share them as open-source tools. “We plan to make our algorithms publicly available and easy to use for the research community,” says Dr. Goubran. For patients and clinicians, this could mean improved diagnosis, customized treatments, and better ways to monitor disease-modifying therapies currently being studied.

Mapping network changes

Another area of his research involves studying how well different brain regions are connecting with one another. Altered connectivity could signal problems down the road. “In neurodegenerative diseases like Alzheimer’s, a network disorder, there are a lot of changes in function and structure of brain networks, so we’re doing also a lot of work on that front, trying to develop novel signatures of network dysfunction,” says Dr. Goubran.

This research direction has two foci. One is preclinical work in the laboratory to develop newer signatures (read-outs) of network dysfunction in Alzheimer’s models. The other is developing new computational techniques to analyse functional and diffusion MRI scans in order to better understand and map network changes in-vivo and develop biomarkers. Dr. Goubran was recently awarded a New Investigator Grant from the Alzheimer Society of Canada to help support this work. He collaborates closely on these projects with Dr. Bojana Stefanovic, Dr. JoAnne McLaurin, Dr. Jennifer Rabin, and Dr. Black, as well as groups at McGill and Harvard universities.

The hope is that when altered connectivity between brain regions is detected, a combination drug treatment that targets abnormal buildup of two proteins involved in Alzheimer’s disease – amyloid and Tau – will slow deterioration of key cognitive networks or, if caught early enough in the pre-symptomatic stage, may be able to restore normal connectivity and cognition.

“We’re hoping our work will lead to larger scale efforts to develop combined therapies that will eventually get to the clinic and really push the development of personalized medicine for neurodegenerative diseases,” says Dr. Goubran.

The post Who will get Alzheimer’s? Sunnybrook scientists advancing research to answer this question appeared first on Your Health Matters.

As a volunteer with St. John Ambulance Therapy Dog program, Jenny and Wilson have dedicated time in Sunnybrook’s Dorothy Macham Home with Veterans who have advanced dementia. When the pandemic hit, she and Wilson pivoted to providing virtual visits to those in Sunnybrook’s inpatient psychiatry unit.

“I was a little worried about how Wilson and the patients would interact on camera, but with some tips from other St. John handlers, decided to try it. I discovered if I placed a treat in front of the iPad, Wilson sat patiently, optimistically looking directly into the camera. After the first session, I could see how well it was working. Someone who was really struggling on the other side of the screen was interacting with us and smiling. I provide a list of questions for patients to promote conversation, show them pictures of Wilson as a puppy and Wilson does a few tricks. One of the favourite questions is, ‘what is something funny Wilson has done?’ When they find out he has helped himself to an entire pizza that was left on the counter for my son’s lunch, we share a good laugh. At the end of the visit, I hear from many patients that we have made their day. In turn for mine, I feel the same.”

Jenny says volunteering with Wilson allows for a unique point of connection. “The patients and I often talk about their own pets, or sometimes one they have lost which can evoke a lot of emotion. We talk about how having a dog can help their path to recovery by getting them out for walks and opening them up social interaction with other dog owners or dog lovers that stop for a visit. Many are interested to learn how they can become involved in volunteer therapy dog programs with their own pets.”

Jenny usually spends between five to 15 minutes with each patient, and volunteers weekly. With a love of art, Jenny also draws sketches of Wilson on postcards and sends them to patients she has connected with as a touching memento of their time together.

“I’m trying to give someone a positive break or moment in their day. Personally, I feel volunteering has also improved my own happiness.” Jenny says National Volunteer Week is a reminder that the time and efforts of volunteers everywhere are impactful and worthwhile. “I get a lot of satisfaction by helping others.”

Sunnybrook is grateful to have wonderful, dedicated volunteer therapy dog teams working with patients and residents on all our campuses from St. John Ambulance and Therapeutic Paws of Canada. 

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