Against the Dying Light

CHAPTER 2

Research

Close your eyes




Close your eyes and picture the brain as a large network.

That network is constantly communicating between various regions in order for you to simply say, 'I'd like to play the ukulele,' or, 'I'd like to remember a piece of music,' and then from that music, be able to play the ukulele. That process involves everything from visualizing the notes, to capturing the rhythm, to manipulating your fingers just so.

All that work involves multiple regions of the brain. That's an entire network that needs to collaborate to enable something to happen. And that goes for everything you do - from the most complex motor and thinking tasks, to your seemingly simple daily routines.

So, when we talk about dementias, we are talking about these vital networks being fundamentally destroyed, making all tasks more difficult or impossible.







564,000

Canadians currently living with dementia.

937,000

The number of Canadians who will be living with the disease in 15 years.

1,100,000

The number of Canadians affected directly or indirectly by the disease.




It is important to keep in mind that 'dementia' is not a specific disease - it is a term describing a range of symptoms associated with a decline in thinking skills. Alzheimer's disease accounts for 60-80 per cent of dementia cases. Vascular dementia, which occurs after a stroke, is the second most common type. But there are many other conditions that can cause symptoms of dementia, including some that are reversible, such as thyroid problems and vitamin deficiencies.

All of them, however, can destroy lives.

At Western, researchers are working across the spectrum of dementias - from its roots at the cellular level to its inevitable ending at the bedside, from patient behaviour to caregiver support, from early small signs for detection to big questions about end of life. In the crowded field of Alzheimer's research, Western has carved a niche with its collaborative, optimistic spirit that permeates the pursuit, with hopes their work may reveal keys to combating the disease in the future, while simultaneously easing the burden on those in the present.





Meet Some of the Team




Dr. Rob Bartha is a professor in the Department of Medical Biophysics (Schulich School of Medicine & Dentistry) with cross appointments in Medical Imaging and Psychiatry.

Dr. Michael Strong is Dean of the Schulich School of Medicine & Dentistry. He holds the Arthur J. Hudson Chair in ALS Research.

Dr. Greg Dekaban is a professor in the Department of Microbiology and Immunology (Schulich School of Medicine & Dentistry).

Dr. Jane Rylett is a professor in the Department of Physiology and Pharmacology (Schulich School of Medicine & Dentistry).

Dr. Marco Prado is a professor in the Department of Anatomy and Cell Biology (Schulich School of Medicine & Dentistry), with a cross appointment in Physiology and Pharmacology.

Dr. Vania Prado is a professor in the Department of Anatomy and Cell Biology (Schulich School of Medicine & Dentistry), with a cross appointment in Physiology and Pharmacology.

Susan Hunter is a professor in the School of Physical Therapy (Health Sciences).

Nárlon Boa Sorte Silva is a PhD student in the Department of Kinesiology. Dr. Robert Petrella is a professor in the departments of Family Medicine (Schulich School of Medicine & Dentistry) and Kinesiology.





The Problem is Simple - Yet Complex




The problem is simple - yet complex. Physicians do not treat the fundamental causes of Alzheimer's disease because they do not know what they are. And because they do not know what they are, they are not certain what to look for at the earliest stages. So symptoms creep across patients, slowly, often unnoticed or unconnected by loved ones, allowing the disease to progress unchecked until a diagnosis is made a decade or more later. By then, the damage has been done.

That is the foe.

There are many approaches to Alzheimer's disease research worldwide, however, much of that research focuses on the later stages of the disease. This is primarily due to an inability to accurately diagnose Alzheimer's early in its development. Western researchers are on the other end of the disease, looking to identify the earliest changes in the brain, including:

  • Studying Alzheimer's disease progression in cells, tissues and intact areas of the brain;
  • Investigating mechanisms that regulate amyloid peptide (a protient fragment found in the brains of Alzheimer's patients) production and deposition in the brain in order to understand the consequences these processes have on neuron function and communication;
  • Advancing imaging of the pathological hallmarks of the disease through the use of established animal models;
  • Developing new models that will mimic the neurochemical deficits in Alzheimer's disease, allowing the detection and imaging of metabolic markers related to early neurochemical dysfunctions;
  • Translating basic discoveries in biology and imaging into clinical practice to benefit patients with Alzheimer's disease; and
  • Evaluating therapeutic effects on in vivo models (inside a living organism) and in patients.

If we can get to the disease sooner, we're likely to make a meaningful impact on changing its course. On one hand, we often talk about actually stopping it, right dead in its tracks, and then there wouldn't be any further progression. That's certainly a Holy Grail every researcher speaks about. But even if we could significantly slow the rate of the progression of the disease, that would be a gain because it would create time.





Strength lies not necessarily in numbers


It is in communication, collaboration and connection.

The scientific community has faced a lot of challenges in Alzheimer's disease, particularly on the treatment side. But there is hope as researchers are working together to create change.

Over the last 10-15 years, the amount of collaboration has increased - not just at Western, but across the city, and on national and international levels. We're starting to see groups coming together to answer really tough questions.

For instance, recruiting patients is always difficult in studies. Some sites are excellent at recruiting patients for studies, others struggle, but when 10, or 15, or even 100 sites work together to recruit people to studies, we can answer questions much more quickly and much more effectively. Western is continually gaining strength and momentum in this collaborative research effort.

When those familiar with Western speak of our Alzheimer's research, their minds turn to the Schulich School of Medicine & Dentistry, Robarts Research Institute and the Faculty of Health Sciences as logical stops. And that would be safe as much of the university's work is centred there. However, there are dozens of researchers across nearly every faculty working on some aspect of the disease.

Western brings together a broad range of researchers focused across the spectrum. The work ranges from understanding the basic biology of what goes wrong at a cellular level, to using imaging as a means of looking deeper into the brain than we ever have, to translating that work into animal models to look at different treatments, to working at the bedside with patients and caregivers. Western researchers are interested in so much: How you walk. How you move. How you exercise. How you learn. Where you live. How you age.

Ask any researcher on this campus; no one is able to be an expert in all areas. So, Western employs a team of investigators that come together to tackle a problem that one of them, alone, simply wouldn't have enough expertise to tackle. Collaboration, at that level, is absolutely essential to making progress.




50,000,000

The budget the Canadian Institutes of Health Research invests in dementia research.

$1,400,000,000

The annual cost to Canadians to care for those living with dementia.


Written by Jason Winders
Director, Editorial Services in Communications and Public Affairs at Western.


Challenges of mobility aids and dementia explored


It seems counterintuitive that the use of a mobility aid, such as a cane or a walker, can actually increase the risk of falls in older adults. Yet in individuals with dementia, that's exactly the case. In fact, people with dementia are three times more likely to suffer a fall when using a mobility aid versus not using one at all.

"One of the theories is that having to use a mobility aid is multi-tasking," Physical Therapy professor Susan Hunter explained. "Using a mobility aid means you need to have a lot more cognitive finesse and capacity to use the aid; you need to be able to maneuver around obstacles."

Hunter often makes a comparison with texting and driving. "How many things can you do at the same time and not cause an accident?"



Susan Hunter

Previous research completed by Hunter looked at how much extra cognitive work is required when using a mobility aid. In healthy older adults, using an aid increased one's cognitive burden only slightly. But for people with dementia, the increase was substantial - upwards of 35 to 40 per cent.

Now, Hunter is leading an U.S. Alzheimer's Association-funded study to dig deeper into why this is so.

Hunter and her team of researchers, which includes two Western colleagues, as well as partners at the University of Montreal and Curtin University in Perth, Australia, are conducting a series of walking tests with three distinct groups of people - individuals with mild-to-moderate dementia, a healthy older adult group (50 years and older), and a cognitively young adult group (individuals in their 20s). Of the 30 'novice' participants - those who are not currently using a mobility aid - half will use a cane during the walking tests, and half will use a four-wheeled walker.

The 30 experienced mobility aid users with Alzheimer's disease will similarly be broken into two groups - half with more than six months experience using a cane, half who have used a four-wheeled walker for more than six months. The individuals with Alzheimer's disease will be recruited from the McCormick Home in London, a long-term care facility which has the largest day program in southern Ontario for people with dementia.

Participants will complete straight-path walking tests of six metres in length, as well as complex-path walking tests, which include walking in figure-eight patterns and around obstacles. They'll also experience multi-task conditions - talking and walking at the same time while using a mobility aid, for instance. The complex-path walking conditions are of particular interest, Hunter said, because there is limited research on the relationship between complex walking conditions and cognitive load in people with Alzheimer's disease.

"If I have people walk in a straight line, there isn't much difference between the person who has dementia and cognitively healthy people," Hunter said. "But if I ask somebody to walk around obstacles, that's where the two groups spread wide apart. It's much harder for somebody who has dementia to walk in a complex pattern, as well as maneuver around obstacles."

Various measures will be used in quantifying the results, including the participants' gait velocity, cognition, vision, balance, strength and fear of falling.

"We're actually quantifying what their walking looks like and what changes happen," Hunter said. "We know it takes more cognitive burden to use an aid. But is that associated with markers of instability? Do people actually become more unsteady?"

The study represents a shift in thinking about fall prevention and challenges the current rehabilitation practice by seeing the use of a mobility aid as a complex cognitive task. In a pilot survey with physiotherapists, none indicated they included executive function or cognitive load in their assessments with a patient. The immediate benefits of Hunter's study, then, will be to show the importance of taking those factors into account when prescribing a mobility aid to an individual with dementia.

"The goal is to develop an assessment protocol that can be used in clinical practice and that is specifically designed for people who have dementia, accounting for factors unique to those individuals, like cognition and vision changes," Hunter said.

"There's a knowledge gap where, on the one hand, you're providing a person with dementia with a mobility aid that can provide physical support. But then you're giving somebody potentially new complex tasks. Do we follow people long enough to say that they're safe? Can we train people better in using the aids?"


Written by Todd Devlin






Mind-body maximizes benefits of exercise to seniors


By 2035, a third of the Canadian population will be over 60 years old. And Kinesiology PhD student Nárlon Boa Sorte Silva wants to make sure every one of them stays active and engaged in life via exercise.

In a recent study, Boa Sorte Silva showed that mind-motor training - an activity that simultaneously engages both cognitive function and movement - used in association with regular exercise helped older adults stave off the effects of dementia more than just regular exercise alone. These findings could open the door to new physical activity programs and approaches for older adults.

"When we think of older population's needs, in terms of overall health, it is exercise. But we also need to think of cognition," Boa Sorte Silva explained. "We want to target cognitive health as well as overall health."



Nárlon Boa Sorte Silva and Robert Petrella

Originally, Boa Sorte Silva arrived at Western in 2014 for a three-month research project with Schulich School of Medicine & Dentistry and Kinesiology professor Dr. Robert Petrella. He has since been fast-tracked for his PhD in Kinesiology.

In his recent research project, conducted in association with Petrella, Boa Sorte Silva followed two groups taking part in exercise programs: One group focused on exercise alone. A second group focused on exercise combined with mind-motor training, in this case, a square-stepping exercise on a gridded floor mat.

With the mind-motor training, subjects performed stepping patterns that slowly got more complicated. They watched a pattern and then attempted to repeat it.

Boa Sorte Silva recently presented his research at the Alzheimer's Association International Conference this past month in London, England.

The study found the group that combined exercise and mind-motor training showed greater improvement in cognition, global cognitive functioning and memory. As a side benefit, Boa Sorte Silva said group participants were more socially engaged, as the mind-motor training required participants to encourage and help each other out.

"They become more self-aware of the importance of training cognition and mobility," he said.

Petrella agreed. Earlier studies showed that older people who are more socially engaged tend to be more cognitively intact and enjoy life more.

"It's not just about exercise. We know epidemiologically exercise is associated with having better cognitive function. But if you can think about other ways people improve their cognitive ability in the long term - such as puzzles and dancing - all those things may have an impact," Petrella said.

In certain regions of the brain, mobility and cognitive functions co-exist. If you can make a change to that part of the brain, you could can get dual benefit. "And we're finding that," Petrella said.

Dementia numbers facing Canada are daunting. While 564,000 Canadians are currently living with dementia, that number will grow closer to a million within 15 years. Almost seven in 10 of those diagnosed with dementia over the age of 65 are women. Current, dementia-related expenses to the Canadian economy stand at $10.4 billion.


Written by Paul Mayne
Reporter, Editorial Services in Communications and Public Affairs at Western.