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Researchers profiles

Discover exciting new avenues of research in the field of cognitive diseases currently being explored by recipients of the Alzheimer Society Research Program (ASRP):

Alex Mihailidis
Putting technology to work for people with cognitive disease

Dr. Alex Mihailidis is looking to improve computerized devices for people with cognitive disease, which could increase the quality of life and help them live as independently as possible.

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According to Alex Mihailidis, a biomedical engineer, the technology to help people with cognitive disease is currently limited to mobile applications to manage medication, or to GPS tracking devices for people subject to wandering.

But Mihailidis, who is also a professor of occupational therapy and computer science at the University of Toronto, dreams of all kinds of computerized devices to help people with cognitive illness to live as independently as possible.

Funded in part by the Alzheimer Society Research Program, Dr. Mihailidis leads a team of computer scientists, gerontologists, psychologists, bioengineers and speech-language pathologists in hopes of developing all kinds of advanced devices. . The “talking bathroom”, one of their achievements, detects the person who shows signs of confusion and speaks to him in a soft voice if he forgot the soap or did not open the tap. Sensors and videos are also installed in front of the sink to demonstrate the proper way to wash your hands.

The team is also working on the development of an interactive robot called Ed, which looks like a vertical hoover crowned by a face formed by a flat video screen. The robot can follow the person in the kitchen and give them voice messages on how to proceed to perform daily tasks, such as preparing a cup of tea.

Preliminary testing at the Toronto Rehabilitation Institute suggests that people with cognitive illness are willing to interact with Ed and follow what he says. Future trials will determine how well robot services help people with cognitive disease perform specific tasks.

“We are still at the research stage. These technologies are complex, says Mihailidis. Our goal is to work with users to validate the relevance of these devices, and take them out of the lab for use in the real world. “

But before that happens, we need to change the way we think about these new technologies.

“They should no longer be considered as medical devices, but as devices among others in the electronics market,” he continues. You have to be able to buy them in the same place where we find all the other consumer electronic devices. “

Barry Greenberg
Focus on the prevention of cognitive diseases
Dr. Barry Greenberg is exploring ways to prevent the disease before clinical symptoms occur.

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The old adage that prevention is better than cure is very relevant to Alzheimer’s disease, according to Dr. Barry Greenberg, Director of Strategy, Toronto Dementia Research Alliance.

“At the risk of discouraging many, I must say that we should not expect to find a cure soon,” says Dr. Greenberg. It is more realistic to focus on prevention. Once the diagnosis is made, brain degeneration is already at an advanced stage. “

“Doctors can only manage the symptoms,” says Dr. Greenberg, who is also Director of Drug Discovery and Development at the Department of Neuroscience at the University Health Network in Toronto.

Redundant networks of the brain compensate for the effects of neuron death, which is why it is estimated that it takes 10 to 20 years for cognitive disease to become evident. But if we can detect people in pre-symptomatic phase, according to Dr. Greenberg, it will be possible to delay or even stop the progression of the disease through medication and changes in lifestyle.

The specialist continues: “The irony is that if this assumption is correct, there may already be drugs that have not been conclusive in clinical phase, but could have played a preventive role s’ they had been administered in presymptomatic stages. But we have not been able to track these people. “

For this reason, Dr. Greenberg has high hopes for research into presymptomatic risk markers, including genetic mutations, cerebrospinal fluid biomarkers, and brain scintigraphy, to uncover sticky aggregates that may play a role development of Alzheimer’s disease. This also includes other biomarkers, which, if validated, could provide accessible, inexpensive and non-invasive means of risk assessment.

Researchers, many of whom work in Canadian research centers, are experimenting with an experimental drug to prevent cognitive decline in participants who still have no symptoms of the disease.

“The ultimate goal is to prevent disease before clinical symptoms occur,” says Dr. Greenberg. This seems to me much more feasible in the near future than to cure the disease once appeared. “

David Stock
The impact of brain damage on menopause and memory
Dr. David Stock investigates the links between brain trauma and early menopause in the hope of finding preventive treatments for Alzheimer’s and related diseases.

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Early and sudden menopause may increase the risk of cognitive disease. Studies suggest that brain damage can have the same effect. The researchers are now studying the possible links between the two phenomena likely to lead to preventive treatments.

Dr. David Stock, a postdoctoral researcher at the Acquired Brain Injury Research Laboratory at the Toronto Rehabilitation Institute, is investigating whether and how brain injury can affect the age of menopause.

According to previous research, the menstrual cycle of women who experience brain injury can be disrupted or interrupted for a long time. Dr. Stock wants to determine if a brain injury can also lead to early menopause.

During menopause, estrogen levels decrease. This is important because the regions of the brain involved in the formation of new memories, such as the hippocampus, are filled with estrogen receptors. In fact, this hormone is one of the keys to the functioning of the hippocampus, and this region of the brain is often the first to be targeted by cognitive diseases.

On the other hand, estrogen in the brains of men does not undergo such a pronounced decrease. The male sex hormone, testosterone, is turned into estrogen in the brain. Since testosterone levels do not decline much in men as they age, their hippocampus continues to function.

Funded in part by the Alzheimer Society Research Program, Dr. Stock will recruit women in Toronto hospitals who have suffered brain injury. He will then closely monitor their hormone levels and menstrual cycle to discover markers of early menopause.

If they discover a pattern that seems to indicate a link and subsequent studies confirm it, hormone replacement therapy may be considered.

“I know that hormone replacement therapy is controversial,” says Dr. Stock. According to large clinical trials conducted in the early 2000s, it may be a risk factor for cognitive disease. But the problem may be the timing of the start of treatment.”

If women with brain injury who had been involved in early menopause could be screened for, they could start hormone replacement therapy before their bodies adjust to lower levels of estrogen.

Dr. Stock hopes to present his results within three years.

Donald Weaver
How to make a medicinal molecule for Alzheimer’s
Dr. Donald Weaver uses computer-aided design to develop drug-based drugs that could stop the progression of Alzheimer’s disease.

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Wanted: A small molecule that mixes well with water and fat. Must be of perfect size and shape to bind to beta-amyloid molecules in the brain and prevent them from forming toxic aggregates.

This molecule is a bit like the holy grail of pharmaceutical research in the world of Alzheimer’s, because it has the extraordinary potential to prevent beta-amyloid from aggregating and killing brain cells.

The problem is that even if this molecule already exists, researchers have not found it; and if it is possible to synthesize it, we must discover how. But Dr. Donald Weaver, director of the Toronto Western Research Institute, is hopeful of getting there.

“Many labs around the world are trying to find drugs for Alzheimer’s disease. One day or another, one of these labs will succeed, “he says.

With support from the Alzheimer Society Research Program, Dr. Weaver is leading a laboratory specializing in the computer-assisted design and development of molecule-based Alzheimer drugs. Dr. Weaver and his team use computers to map the three-dimensional shape and size of beta-amyloid receptors. Receptors are structures on the surface of a molecule that bind to other molecules.

By knowing the shape and size of the receptors, Dr. Weaver will be able to search for or synthesize the binding molecules, which will make toxic aggregation of beta-amyloid impossible.

But these drug molecules must first cross the protective blood-brain barrier. This is the reason why you first have to mix them with water and fat. The barrier is difficult to break because our blood is water-based and our brain is fat-based. Most molecules are soluble in one or the other.

“You have to incorporate that delicate balance,” says Dr. Weaver. The molecule must have some solubility in the blood and in the brain. It can then cross the barrier by passive diffusion. “

His laboratory is now testing three promising molecules while continuing work on several others.

“We are all looking for the next generation of compounds for Alzheimer’s disease. We will do it one day and I hope it will be the work of our laboratory, “concludes Dr. Weaver.

Eva Vico Varela
Optimize the potential of deep brain stimulation
Eva Vico Varela is studying the effect of deep cerebral electrical stimulation on Alzheimer’s disease and the most effective approach to applying it.

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For more than twenty years, deep cerebral electrical stimulation has helped control tremor in people with Parkinson’s disease. Researchers now believe that electrical stimulation could also improve the memory circuits of people with Alzheimer’s disease.

However, there is a problem. Physicians know the frequency, interval, and duration of electrical stimulation needed to control tremors most effectively, but not how to use them to affect memory.

Eva Vico Varela, a doctoral student in neuroscience at McGill University, wants to find out.

Funded in part by the Alzheimer Society Research Program, Dr. Vico Varela will study, in the coming year, deep brain stimulation in genetically engineered mice as a model of Alzheimer’s disease. She will study their brain by digital scanning by simultaneously doing various tests of electrical stimulation at several frequencies, intervals and durations.

“I want to see if changes in the frequency and strength of brain waves are associated with recovery or memory consolidation in mice,” she says.

Vico Varela will also have a series of memory tests for the mice before and after the deep brain stimulation.

It will apply impulses to the fornix, which is a C-shaped structure buried deep in the brain. The fornix consists of axons, which are long fibers that unfold from the brain cells and carry the outgoing messages.

The fornix serves as the main link between the hippocampus and the rest of the brain. This is a crucial link since the hippocampus plays an important role in short and long-term memory consolidation and spatial memory..

An earlier study of healthy rats treated with electrical impulses demonstrated improved memory. The work of Dr. Vico Varela will demonstrate whether it is possible to obtain the same results with mice with Alzheimer’s disease and, if so, how exactly these impulses should be applied.

“This treatment will not provide a cure. It may not be able to improve memory either. But it could help slow down the decline and improve the quality of life for people with cognitive disease, “she says.

Sarah Atwi
Strengthen brain networks after a silent stroke
Sarah Atwi is investigating whether exercise can strengthen weakened connections in the brain due to a silent stroke.

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One in ten 63-year-olds have had a silent stroke, which doubles the risk of cognitive disease. Most will not realize it since none of the symptoms of a typical stroke will manifest, such as numbness or speech disturbance

Typical strokes occur in brain regions of the gray matter that control specific functions, such as movement or speech. Silent stroke, on the other hand, usually attacks the white matter, which acts as a highway in the cerebral connection of the various regions of the gray matter. Therefore, no faculty is compromised.

However, silent strokes weaken the connections necessary for general functioning. In many cases, they cause problems in planning, decision-making and speed of reasoning.

While there is no known cure for these symptoms or the risk of cognitive disease, researchers believe that exercise is the key, says Sarah Atwi, a doctoral student in neuroscience at the University of Toronto.

This is because exercise helps to keep the blood vessels healthy and increase the flow of blood that circulates oxygen and nutrients to the brain. Exercise is also believed to help increase the level of a protein called neurotrophic factor derived from the brain, known to contribute to neuronal growth.

“It is therefore possible to combat age-related cognitive deficits,” says Atwi. I would now like to know if exercise can strengthen weakened connections in the brain due to a silent stroke. “

Funded in part by the Alzheimer Society Research Program, Dr. Atwi currently recruits 60 people who have had silent strokes, as determined by brain scans. Ms. Atwi will use magnetic resonance imaging devices to scan participants’ brains during various cognitive tasks after a six-month and one-year physical activity period. Imaging devices will measure signals indicating blood oxygen levels in brain networks commonly used for cognitive tasks. The higher the signals, the more active these networks are.