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Shedding light on the Alzheimer’s brain

Thursday, October 11, 2012

ROBARTS SCIENTIST ROBERT BARTHA BELIEVES IMAGING IS KEY TO EARLY DETECTION AND PREVENTION

By Hailey Eisen

As anyone who knows a person living with Alzheimer’s disease can attest, the disease has devastating implications for the individual who slowly slips away into confusion and memory loss, and for the family and caregivers who carry the weight of this irreversible diagnosis. It’s with this in mind that Robert Bartha, PhD, a scientist with Robarts Research Institute and Associate Professor of Medical Biophysics, Schulich School of Medicine & Dentistry, works fervently within the Imaging Research labs at Robarts. With a primary focus on diseases of the brain, and a particular interest in Alzheimer’s disease, Bartha anticipates a day when early
detection through advanced imaging techniques followed by drug treatments will be successful in bringing this debilitating disease to a halt.

Currently, Alzheimer’s is only diagnosed through clinical and neurocognitive assessments (i.e., memory testing, problem solving, etc.) and a definitive diagnosis is only possible after death through an autopsy.

According to the Alzheimer’s Society of Canada, if there is no medical breakthrough within the next 25 years, more than four million Canadians will have developed Alzheimer’s disease or a related dementia. This will be a dramatic increase from 2010 when 500,000 Canadians were reportedly living with the disease. The economic implications are equally as shocking: with
2010 reports indicating the cost of dementia in Canada at $22 billion annually, and predictions climbing to approximately $153 billion annually within a generation, if nothing changes.

Things will change, if Bartha has any say in the matter. For years, Bartha and his team have been collaborating with Dr. Michael Borrie, Professor, Schulich Medicine & Dentistry and geriatrician at St. Joseph’s Parkwood Hospital in London, to examine normal elderly adults in comparison to those individuals with mild cognitive impairment (MCI) and those with Alzheimer’s disease. In developing and utilizing new magnetic resonance imaging (MRI) methods, Bartha is
able to observe disease in the human brain and investigate how it progresses.

“We study the anatomy of the brain and how that changes with MCI and Alzheimer’s,” he explains, “we’ve also gone beyond that to look at the metabolism and chemistry of the brain using magnetic resonance spectroscopy (MRS).”

The ultimate goal: establish a noninvasive technique to identify subtle changes in the brain, which indicate the presence of Alzheimer’s long before an individual experiences cognitive decline or memory loss. “Unfortunately, now, by the time someone experiences symptoms of Alzheimer’s, irreversible damage has already taken place,” Bartha explains. “The disease takes
hold decades before the first symptoms appear.”

Bartha and his team continue to receive accolades for their groundbreaking work. In 2008 they utilized MRI scans obtained through the Alzheimer’s Disease Neuroimaging Initiative sponsored by the National Institutes of Health , to track anatomical changes to the brain based on high precision techniques they had developed in-house. In doing so, they identified clear evidence that increases in the size of the brain ventricles (fluid filled cavities in the brain) can be directly associated with cognitive impairment and Alzheimer’s disease. “Those findings gave us hope that a technique like the one we developed could help predict which patients experiencing
MCI would go on to have Alzheimer’s disease.”

More recently, Bartha and his team were able to take brain imaging to the next level by utilizing MRI and MRS technology to examine the brain’s metabolic function. Their most significant findings, published in the journal Neurobiology of Aging in 2011, showed reduced levels of hippocampal glutamate (the major excitatory transmitter in the brain) in individuals with MCI and Alzheimer’s. “From this we were able to hypothesize that neurons in the brain’s hippocampus
were actually becoming dysfunctional before dying,” he explained. “Going forward, the  measurement of glutamate should help us predict, more accurately than anatomical imaging, which patients are at higher risk for Alzheimer’s disease than others.”

All of this forms the basis for even more exciting research using Robarts’ 7.0 Tesla MRI machine, the only one of its kind in Canada. Providing higher magnetic field strength than the 1.5 or 3.0 Tesla machines typically used in hospitals, the 7.0T scanner makes it possible to view the entire brain with increased clarity, allowing them to better visualize of areas such as the hippocampus
where metabolic change is taking place. “When you’re not sure what you’re looking for, the increased resolution is extremely beneficial,” says Bartha. “But, once we identify glutamate as a biomarker, we’ll be able to develop techniques that enable clinicians to measure for it using a
3.0T scanner, which they’re more likely to have access to.”

Translating his research efforts to the clinical setting is a key component of Bartha’s work. His group is working to develop a user-friendly interface that can be utilized by doctors to improve patient care. The goal of this tool would be to enable physicians to enter patient data (derived from MRI scans) then retrieve an analysis based on key markers and compare those to the average for that population. “We are hoping to work with the Centre for Imaging Technology Commercialization (CImTeC), an initiative that helps imaging scientists converge with small and medium-sized Canadian enterprises.”

Bartha’s team is also involved in clinical drug trials attempting to identify, via imaging techniques, drugs that may be able to successfully stop the progression of the disease. Finally, they are also working to develop a new class of contrast agent that would work with MRI scans to identify early changes in Alzheimer’s disease within the brain. “The success of this project is still many years from being realized, and the outcome remains high-risk because we are not sure if it’s going to work,” he says.

Still the group forges ahead, keeping in mind the ultimate goal of a future without Alzheimer’s disease. “There is a great feeling of personal satisfaction that is achieved with each new discovery and problem that is solved particularly those that lead to the potential for a
positive impact on health care.”


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