Paving the Way

From comparing the effectiveness of therapies used in care homes to mapping the way metals interact with the brain, these Canadians are making waves in dementia research

Dr. Jennifer Watt

Clinical research is important in the world of dementia care: having data based on how people respond to various therapies and methods of care gives medical professionals and caregivers real-world insight into how to best serve people living with dementia. But with so many researchers testing different approaches in different studies, it’s nearly impossible to get a real handle on which therapies produce the most consistent results.

This is a problem that Dr. Jennifer Watt, a geriatrician at St. Michael’s Hospital in Toronto and an assistant professor at the University of Toronto, set out to solve with a study that amalgamated data from 189 different research projects from around the world. Watt is the lead author on an October 2019 paper that compares the efficiency of both pharmacological and non-pharmacological interventions that deal with the complex behavioural and psychological symptoms of dementia. Specifically, Watt’s systemic review looks at how effective each strategy is at addressing the symptom of agitated or aggressive behaviour in people living with dementia, which is often the result of an unmet need.

“Both myself and many of my colleagues have seen first-hand how different types of interventions can lessen symptoms of aggression or agitation, but we didn’t have any good studies comparing the outcomes of medication and non-medicated treatments,” Watt says. “That’s why we embarked on the study that we did.”

Watt’s paper ranked the effectiveness of several potential interventions ranging from animal therapy (which ranked quite low) to outdoor therapy (the highest-ranking method on the list). Several drug treatments, like antipsychotics, ranked in the top third of the list. Still, given the potential side-effects of many of the listed medications, the ultimate finding is that caregivers should prioritize the high ranking non-pharmacological interventions such as massage, touch therapy and spending time outdoors.

Dr. Zahra Goodarzi, a fellow geriatrician and assistant professor at the Cumming School of Medicine at the University of Calgary, worked with Watt on the study. She designed an infographic depicting each treatment’s efficiency so that caregivers can easily discern which interventions have had the most success, statistically speaking.

“We wanted to create something that would be useful,” Goodarzi says. “The best part of it is that this is our best evidence. This is all of our knowledge distilled together and ranked.”

Based on their clinical experience, both Watt and Goodarzi say they weren’t surprised by how effective the non-pharmacological interventions ranked in the study. Based on first-hand experience, many care professionals have long advocated for a shift towards addressing the root causes of agitation and aggression by providing a sense of comfort and security through non-pharmacological therapies rather than eliminating those symptoms through drug interventions. But this is the first time that data has shown how effective these therapies are in comparison to medications. Watt is pleased that her study will validate what many caregivers have already been practicing.

“People have long believed that these non-medicated interventions work, we just never had the evidence to support what we believed,” Watt says. “We can use this study to make a case for why we need to be using these non-pharmacological interventions clinically and why we need the resources to implement them successfully.”

Kelly L. Summers

Kelly L. Summers doesn’t specialize in matters of neurology, but she’s working on research that may have a tremendous impact on the brains of people living with dementia. The PhD candidate from the University of Saskatchewan is most interested in the ways that metals interact with the human body, including how a metal imbalance can affect and impair brain function.

Summers’ work is focused on the amyloid β peptide, a specific amino acid chain that can become misfolded in the brain, forming clumps on the outside of brain cells. These sticky clumps can trap metals, specifically copper, within them. Under the supervision of Drs. Ingrid Pickering and Graham George, professors at the University of Saskatchewan and Canada Research Chairs, Summers is studying how copper interacts with these peptides and how that interaction might contribute to the development of Alzheimer’s disease.

Last year, Summers published a paper titled “X-ray Absorption Spectroscopy Investigations of Copper(II) Coordination in the Human Amyloid β Peptide.” Summers and her team’s findings may further our understanding of how the amyloid peptide binds to copper, which could indirectly predict how to remove the copper with drugs.

“One avenue that we explored is looking at how we could use some small molecule or drug that would be able to remove the copper where it’s bonded with these peptides in the brain,” Summers says. “There’s been some promising results in mice where these drugs we’ve looked at seem really effective.”

Summers isn’t suggesting that the copper that binds to the peptides is completely responsible for Alzheimer’s, but it could be part of a host of problems that contribute to the disease. Since the copper that sticks to the peptides is leached from other parts of the brain to create an imbalance, part of the research is to figure out how that imbalance may contribute to the disease.

“This is one of the pieces of the puzzle and we know that the peptides shouldn’t be there and the copper should not be stuck there,” she says. “Whether that’s happening because other things are going on or if it’s the root cause of the disease, we don’t yet know.”

The ultimate goal is to develop a drug that either stops the copper from binding to these peptides or pulls the copper from the peptides to restore it to other parts of the brain.

In the lab, Summers is now working with an Alzheimer’s model mouse and spectroscopy equipment, mapping out the copper in the animal’s brain before and after it is treated with copper binding drugs. She is hopeful that the evidence from the mouse trials will help lead to a similar drug suitable for human use.

“There’s some really interesting new evidence that shows that metals might have a role in how we store and form memories, so it makes sense to me that metals would have a significant role in the disease,” Summers says. “If we can get those metals under control with some relatively simple drugs, it could have a fairly significant impact on slowing disease progression and making some of the cognitive symptoms less severe.” [ ]