“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.

FNP is a free service that pairs youth aged 13 to 26 with mental health and/or addictions challenges to clinically trained navigators who connect them and/or their families to the services they urgently need.

“We’re running for all the youth we’ve helped. And we’re running for those who need help,” says Kailey, who was one of the first navigators hired at FNP when the program began and has been a keen participant in the race from the beginning.

Navigators are clinically trained mental health professionals who conduct a thorough assessment of concerns, client needs, and provide expert navigation of the health care and social service system to guide youth and their families to the specialized care that is right for them.

“I’m grateful when I think of the thousands of youth and families we’ve been able to help, who were lost without a path,” says Kailey. “They contacted us. We welcomed them. We had their back. And we stayed in the boat with them.”

The need is great. As many as 1.2 million Canadian youth are struggling with mental illness and 30 per cent of Ontario families are caring for at least one youth with mental illness and/or addiction. Statistics only tell part of the story. “If one person is not doing well, it has a trickle-down effect on the whole family,” says Kailey.

Over the COVID-19 pandemic, she adds, the need has intensified. More than twice as many youth are reaching out directly to FNP. They are dealing with anxiety, depression and addiction, and they and their families are worried about where to find help.

Since its launch in 2013, FNP has seen a 70 per cent growth in the number of youth who have reached out to FNP for help. FNP’s expansion has been made possible by private donors and the more than 60,000 people who have participated in the race, contributing more than $18-million since the first RBC Race for the Kids was held on the grounds of Sunnybrook.

When Kailey first started at FNP, she was one of only two part-time navigators. Now, there are 10 full-time navigators, an intake coordinator, a parent advocate with lived experience and three consulting psychiatrists.

Kailey has witnessed the success of FNP in many forms: from a youth accessing peer support or a live-in program, to a parent feeling less overwhelmed, or a family finding a service that is a good fit.

“Without the RBC Race for the Kids and the support of donors, we would not be able to provide this lifeline for youth and their families,” she says.

This year’s race takes place on September 17.  Participants can join in person at Mel Lastman Square or virtually. To register click here.

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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.

When a person has ventricular tachycardia, faulty electrical signals in the ventricles of the heart cause their heart to beat too fast or irregularly, impeding proper blood flow to the body. “This is a very urgent problem,” says Dr. Fumin Guo, a postdoctoral fellow working in the cardiovascular imaging lab of Dr. Graham Wright at SRI. “Most of these events occur, without previous symptoms, at home or in a public space, not in hospital. And they can be fatal within minutes. We are trying to improve diagnosis and therapy to prevent sudden cardiac death.”

One of the current treatments for ventricular tachycardia is radiofrequency ablation, which involves guiding a device into the heart and using an electrical current to heat up and destroy a small area of tissue that may lead to the abnormal electrical signals (arrhythmia). But about 35 per cent of ablation procedures result in either initial failure or later recurrence.

Preclinical work by Dr. Guo and others in Dr. Wright’s lab is focused on improving the outlook for those with VT in three ways: identifying the underlying structural and functional issues in the hearts of individuals, pinpointing damaged tissue with greater precision, and delivering treatment with more accuracy and efficiency.

The lab has demonstrated success using 3D magnetic resonance imaging (MRI) to guide radiofrequency ablations with improved precision. “Imaging, and in particular MRI, shows great promise in helping to improve management in this patient population, and we are working at the state of the art to look at all aspects from identifying those at risk, to improving the effectiveness of procedures,” says Dr. Wright, who is a senior scientist in the Physical Sciences Platform and Schulich Heart Research Program at SRI.

Dr. Guo recently won the prestigious Polanyi Prize in Physiology and Medicine for his significant contribution to this work. With his background in biomedical engineering, he is developing, using artificial intelligence and computer vision methods, automated image analysis systems that map the heart and pinpoint the damaged tissue. He is also advancing computer algorithms to plan, guide and assess VT treatment.

“Fumin’s work means the image analysis needed to guide procedures will be more repeatable, faster, and hopefully more accessible to others,” says Dr. Wright. “The Polanyi Prize is very prestigious. Winning the prize is emblematic of the clinical relevance of the work and the excellence of Sunnybrook’s program in image-guided, personalized, precision therapy.”

Dr. Wright adds that his lab is collaborating with clinical heart programs and partnering with industry to ensure the preclinical work can be translated to patient care as quickly as possible.

For his part, Dr. Guo is enthusiastic about what lies ahead. “Our ultimate objective is to cure patients with ventricular tachycardia conditions. We want patients to live longer, healthier and happier.”

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