Mind Matters

Dementia isn’t one specific disease, but a way of describing a set of symptoms that are caused by disorders affecting the brain. While Alzheimer’s disease is the most common form of dementia, there are others, including vascular dementia, Creutzfeldt-Jakob disease and dementia with Lewy bodies.

Both short- and long-term memory loss are primary symptoms of dementia, but almost 40 per cent of people over 65 experience some form of mild memory loss, most of whom don’t develop dementia, indicating that it isn’t the only symptom. Other signs include changes in mood or behaviour and challenges with thinking, problem-solving or language that interfere with one’s ability to perform everyday activities.

As for why most people living with dementia are over the age of 65, there are a host of reasons, says Natalie Phillips, a Department of Psychology professor and Concordia Research Chair in Sensory-Cognitive Health in Aging and Dementia.

“It could be years of subtle vascular changes or inflammatory processes in the brain that just take time to manifest themselves,” she says. “And then the natural mechanisms that the brain has to combat these kinds of insults start to weaken as people get older. You also start to develop other health conditions in later age that can amplify the problem.”

Communication breakdown

Habib Benali, a professor in the Department of Electrical and Computer Engineering, describes those potential inflammatory processes in the brain as “cascades.” The Canada Research Chair in Biomedical Imaging and Healthy Aging thinks they could begin decades before an Alzheimer’s diagnosis.

A large part of Benali’s current work at Concordia involves simulating the neurodegeneration of individuals’ brains. His lab does this using artificial intelligence and other highly sophisticated mathematical and computational tools.

The idea is to model the changes or potential changes to the brain long before a possible diagnosis so that doctors can tailor individualized preventions and treatments.

One of the changes that Benali and his team are modelling is the cascade of beta-amyloid, a protein in the brain that is connected to Alzheimer’s. When it clumps together between brain cells, it can eventually form into amyloid plaques large enough to block signals from being transferred between brain cells. This can slow or stop communication between brain cells and may play a role in causing those cells to die, leading to cognitive decline.  

Another protein that is likely key to the development of Alzheimer’s is called tau. Benali and his team are building it into their model as well. In healthy brains, tau regulates the assembly and maintenance of the structural stability of microtubes (known as axons). But in unhealthy brains, it collapses and twists, forming tangled clumps of fibres that prevent nutrients from reaching brain cells. This eventually leads to cell death and, ultimately, to neurodegeneration.

The unhealthy development of beta-amyloid and tau likely starts decades before an Alzheimer’s diagnosis, says Benali. The problem is that by the time a diagnosis is made, it’s often too late to remedy

“This is exactly what I don’t want,” he says. “I want to predict when this degeneration starts because we have enough medications — even today — to stop these processes early.” 

Inner workings

Early detection is also a big part of Stéfanie Tremblay’s work. She currently studies the MRI biomarkers of declining brain health in aging as part of her research at the Department of Physics.

Tremblay is particularly interested in those linkages — or axons — between different brain regions that are important to Benali’s brain-simulation work. They form portions of the brain’s white matter, and she likens them to streets in a city

“There is some evidence that white-matter changes may be a very early marker of dementia,” Tremblay says. “But I’m not looking at its gross loss of volume. It’s more that I’m looking at the state of those streets: Is it a nice road with several lanes or is it a narrow street with a lot of potholes? We can imagine that this has an impact on the speed of transmission, which then impacts brain function.” 

In one of her main PhD projects, Tremblay uses MRI to look at white-matter health within patients with cardiovascular issues but without dementia. Cardiovascular problems are good predictors of developing dementia later on, so Tremblay wants to see if these patients displayed early brain changes associated with dementia.

In her other PhD project, Tremblay uses MRI to look at the axons within people with a family history of Alzheimer’s who don’t have the disease themselves. 

Her projects are ongoing, but she does see changes in white-matter health in both groups, and these changes are associated with some cognitive deficits. “This is important for early detection,” she says. “If we can find which MRI measures are most helpful in detecting early brain changes, this can hopefully be used to intervene earlier and prevent the development of dementia.”

Connecting sensory and cognitive abilities

As important as MRI is in spotting the early signs of dementia, researchers and clinicians also use other detection tools. Natalie Phillips, for instance, typically uses cognitive tests to assess language, learning, memory, problem-solving and multitasking skills in older adults.

In 2005, Phillips played a key role in designing the Montreal Cognitive Assessment, a screening tool that is now considered the world standard for detecting the dementia-risk state known as mild cognitive impairment (MCI). 

More recently, as one of the associate scientific directors of the Canadian Consortium on Neurodegeneration in Aging (CCNA), she has been involved in Canada’s largest study of dementia, called the Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND). It collects a huge range of data on participants at risk for or living with dementia. 

Of particular interest to Phillips is sensory function. Some of her more recent research has looked at why olfactory or auditory loss seems to increase the likelihood of developing dementia. She doesn’t have any answers quite yet, but there are hypotheses.

For smell, one theory is that the brain area that mediates this sense is the same where Alzheimer’s pathology starts. 

For hearing, it’s no doubt quite different, says Phillips.  

“There are probably some common biological causes, but we also know that if you have a hearing loss, your brain is going to be working much harder when you communicate and will need to recruit additional areas to compensate,” she says. “Over the long term, that may start to be a problem if the brain is continually trying to compensate.” 

Those with hearing loss also tend to limit their social lives, says Phillips. “Going out becomes more effortful, it’s harder to hear people at parties, so you might not do those things as often. And we know that social engagement is really important for helping older adults maintain their vitality.”

Exercising the brain

Karen Li, a Department of Psychology professor, is also interested in developing non-MRI methods to detect neurodegeneration. Her research largely focuses on how our ability to be attentive when multitasking changes with age.

Some of her lab’s studies involve getting people to perform an exercise, such as walking on a treadmill, while doing a cognitive task, such as subtracting by threes.

A common conclusion to come out of Li’s lab is that a multitasking test can actually pick up the beginnings of neurodegeneration with more sensitivity than a test that involves only a cognitive task or only a physical activity. This may be due to the overlapping demands for frontal brain regions during walking and cognitive processing.

“So, then we kind of turn that around and say: ‘Okay, if these are the neural circuits that are getting weaker in aging and in neurodegenerative conditions, then we’re going to find ways to strengthen those circuits,’” says Li, who is a member of the CCNA like Phillips.

Li’s multidisciplinary CCNA team looks at interventions to improve cognition and mobility in older adults. They are currently recruiting for a large clinical trial assessing the impacts of moderate aerobic exercise and resistance training, as well as computerized brain training in people at risk for developing Alzheimer’s.

The hope is to build on her own research and that of others to underscore just how important physical and cognitive exercise is to healthy aging brains. “The new clinical trial also brings in additional factors, such as healthy sleep and dietary practices,” says Li. “This helps acknowledge that supporting and improving brain health to reduce the risk of dementia is multifaceted and multidisciplinary.”

Additional risk factors

The kind of collective work that Li’s team is engaged in is vital when trying to detect and prevent such a complicated umbrella of diseases, says Tremblay. “Especially because we know that dementia is more prevalent in populations that are underprivileged and from ethnic-minority communities. We need a stronger collective approach to try to deal with this.”

The good news is that more researchers are recognizing this, she adds.

Take the brain simulation work that Habib Benali and his team have been doing. Benali says that none of it would have been possible without the expertise of Canadian and international scientists working in artificial intelligence, neuroimaging, computational biology, digital health, genomics, Alzheimer’s research, statistics, epidemiology and other disciplines.

Now his team is even trying to include individuals’ environments in brain simulations, which requires a whole other suite of collaborators.

“If I want to follow a person for 10 years and predict if they are going to develop the disease, I have to include their environment within their physiology,” Benali remarks. “That’s a big, big problem, but this is exactly what my team is developing today.”

Those environmental risk factors can be significant. According to a 2020 report published in The Lancet, 40 per cent of dementia cases can be attributed to 12 potentially modifiable risk factors, including air pollution and low social contact. The other risk factors include less education, hypertension, hearing impairment, smoking, obesity, depression, physical inactivity, diabetes, excessive alcohol consumption and traumatic brain injury.

“The main advice as we get older is to remain physically and cognitively engaged, and to find activities that are motivating for you so that you can minimize your cardiovascular risk factors,” says Phillips. “Do everything your grandmother would have told you to do — stop smoking, eat more vegetables, go outside and get more exercise.”

It’s also important to stay hopeful, she adds. Yes, the raw number of dementia cases is going up, but that is also because there are more people over the age of 65 than there were decades ago.

“In Western countries, the percentage of individuals with dementia in that older age range is actually going down compared with 20 years ago,” notes Phillips. “That’s probably because of a lot of the public-health messaging around cardiovascular risk factors and general increases in education and quality of life. So that’s a good-news piece of the puzzle that we have to remember and keep building on.”

Read this cover feature's sidebar “Wide awake: A growing body of research connects poor sleep with dementia”.