Alzheimer's disease Brain Sunnybrook Magazine Sunnybrook Magazine - Fall 2019

Gathering clues about early onset dementia

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In a world-first study, researchers are working to identify when dementia is imminent in people with a genetic predisposition to the disease.


Imagine watching your family members develop cognitive and behavioural decline in their 40s and 50s and die prematurely from dementia. Now, imagine learning that you carry the gene mutation for this dementia, and the same fate awaits you.

“In the prime of your life, you’ll develop changes in behaviour, such as trouble controlling emotions. You may lose your inhibitions. You may shoplift or insult strangers. Eventually, you will lose the ability to communicate,” says Dr. Mario Masellis, clinician-scientist at Sunnybrook and associate professor of medicine at the University of Toronto.

“It’s gut-wrenching to know that your father had this and that your grandmother had this – and now you have the same gene mutation,” says Dr. Brad MacIntosh, neuroimaging scientist, Canadian Partnership for Stroke Recovery at Sunnybrook. “The clock is ticking.”

Dr. Mario Masellis, associate scientist at Sunnybrook’s Hurvitz Brain Sciences Research Program, wants to change that future. That’s why a team of scientists by him is analyzing the characteristics of patients with an early-onset, familial form of frontotemporal dementia in a world-first study.

Frontotemporal dementia is a term for a group of brain disorders that affect the frontal and temporal lobes of the brain, which are associated with behaviour, personality and language dysfunction.

While scientists have been able to pinpoint three major genes responsible for the development of frontotemporal dementia, there’s not a lot known about what happens in the years before symptoms become apparent, Dr. Masellis says. “The whole point is to study people in the pre-symptomatic phase. If you wait too long, the changes [will] have firmly taken hold in the brain.”

In his study, known as the Genetic Frontotemporal Dementia Initiative,  Dr. Masellis and his team are attempting to identify clear brain indicators, also known as biomarkers, that may show the onset of dementia is imminent. Through MRI, the team is tracking blood flow in different regions of the brain. They’re witnessing changes in cerebral blood flow as early as 15 years before expected disease onset.

“We’re seeing potential evidence that certain areas [in the brain] are disrupted,” he says.

Dr. MacIntosh says that during the screening, 20,000 different measurements are taken. Through a procedure called arterial spin labelling – an MRI technique – cerebral blood flow can be measured and labelled as it flows throughout the brain. It offers a very precise look at exactly what is happening on an arterial level.

“The whole focus of the study is on understanding the natural history of the disease and the way the disease progresses over time,” says Dr. Masellis.

As researchers learn more about the variability and progression of the disease, it can help them better design clinical trials for potential treatments. For example, they may have more insight into when drug therapies should be started in a patient or how they should measure the response to treatment.

The study is unique in that it involves a special group of individuals who are at risk of developing frontotemporal dementia.

“The powerful thing here is that unlike other brain disorders, we have the opportunity to study people we know will develop dementia,” Dr. MacIntosh says. “We can learn so much from these people.”

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Anna Sharratt