Different Clues, Same Urgency

How New Science is Helping Spot Risk Before Memory Fades.

It was listening to people with Alzheimer’s disease (AD) that gave Dr. Natasha Clarke the inspiration for her research. She was conducting assessments and leading group therapy sessions, and she noted how her patients would at times struggle to find words or to express thoughts coherently, a trait that veteran clinicians told her was common in cases of dementia.

“And you might talk to someone’s family member, and they would say something like, ‘Oh, looking back ten years, we could see that they had word finding problems.’ But they wouldn’t know if that might be indicative of some kind of problem, because it wasn’t well understood,” said Dr. Clarke in an interview with Mind Over Matter®.

She wondered whether a deeper exploration of speech patterns might have the potential to diagnose AD earlier.

THE IDEA THAT WE CAN USE SPEECH AS A KIND OF WINDOW TO THE BRAIN IS JUST FASCINATING TO ME. BECAUSE IT’S SOMETHING THAT, WHEN IT WORKS WELL, IS EFFORTLESS. BUT WHEN IT STARTS TO GO WRONG, IT CAN GREATLY IMPACT PEOPLE’S LIVES. IT’S SO IMPORTANT.

Now Dr. Clarke has the opportunity to continue pursuing that fascination, with a study of speech, aging, and cognition. It is thanks to a post-doctoral fellowship of $60,000 a year for two years, awarded through the Canadian Consortium on Neurodegeneration in Aging (CCNA) Phase II Women, Sex, and Gender in Dementia (WSGD) cross-cutting program (now called the Sex and Gender Hub), supported by Brain Canada.

The post-doctoral research associate at Université de Montréal is using artificial intelligence (AI) tools and functional MRI (fMRI) to conduct a detailed analysis of the speech patterns of thousands of Canadians who are part of a massive dataset called COMPASS-ND. 

Women tend to do better than men on verbal memory tests, which measure how well people can recall specific words. Dr. Clarke is examining connected speech, which refers to free-flowing, spontaneous speech, as when someone tells a story. It is a subject that has not been studied in detail and so it is not yet clear whether there is a difference between the sexes.

AI tools allow her to rapidly analyze the transcripts of people interviewed in the COMPASS-ND dataset, searching for features that could signal signs of cognitive decline. 

“It’s so rich, because we can extract hundreds of features from speech and then try to find out which are important.”

DR. CLARKE HAS PRELIMINARY FINDINGS INDICATING THERE ARE DIFFERENCES BETWEEN THE SEXES, WHICH WOULD SUGGEST THAT MEN AND WOMEN MAY NEED TO BE TESTED DIFFERENTLY TO GET MORE ACCURATE RESULTS. 

She hopes that her research can pave the way for a simpler, cheaper means of diagnosing AD long before other symptoms appear.

“So, it really opens up opportunities to improve equity in access to care and ultimately to find those individuals who are suffering from the disease earlier. And we need to spot these people as early as possible, so that we can try different disease modifying therapies before it’s too late.”

Dr. Clarke is grateful to Brain Canada for the support, and for the focus of the CCNA’s cross-cutting program that catalyzes explorations on sex differences.

“I think in the past, women have unfortunately not been considered in research as much as they as they should. So this opportunity has been really, really meaningful to me.”

THE GENETIC FACTOR

Dr. Rikki Lissaman received a $60,000 post-doctoral fellowship under the same program. He is also exploring the possibilities of early diagnosis for AD, in his case focusing on the gene APOE. We all have that gene, but for those of us with one copy of the APOE4 variant, the risks of developing AD rise, even more so for those with two copies. In fact, the prevalence of this variant is much greater in women than men.

He has been drawn to studies of that particular gene, and cognition more broadly, since his days as an undergraduate student.

“I’ve always been interested in aging and memory. How does the brain store our memories? How accurate are those memories and how does that change with age? How is that related to changes in the brain? These are questions that I still find fascinating now and probably will when I’m part of a study myself,” he said in an interview with Mind Over Matter®. 

Dr. Lissaman received the funding while a post-doctoral fellow at McGill University and has now moved on to a position as a lecturer in the Department of Psychology at Royal Holloway, University of London.

He is focusing his research on a cohort of mid-life women (defined as between ages 40 to 65) who participated in the Brain Health at Midlife and Menopause Study (BHAMM), which was launched at McGill University. Most of them provided blood samples that could be sent out for genetic analysis, ultimately allowing Dr. Lissaman to compare women who have the risk factor with those who do not. 

Looking for differences in AD biomarkers as well as differences in memory performance and brain function, and employing fMRI to scan brains while participants are doing memory tests is enabling Dr. Lissaman to achieve the goals of his research.

WHAT WE’RE INTERESTED IN SEEING IS WHETHER PEOPLE WHO HAVE THE APOE4 VARIANT RISK FACTOR ARE SHOWING DIFFERENCES IN THE BRAIN YEARS BEFORE THEY WOULD GET A DIAGNOSIS OF AD.

“The more that we understand the nature of that risk, the more likely we are to be able to do something about it.”

He told Mind Over Matter® that preliminary results are showing differences in memory performance between those with the risk factor and those without, and added that it is particularly important to be focusing on women in this study, given that risks related to the APOE4 variant are so much higher for them. 

“The research in this area has the potential to help us better understand aging and the trajectories that lead to dementia, and hopefully interventions that could help delay or prevent it.”

Dr. Lissaman said he was grateful to Brain Canada for the funding support, saying it allowed him to not only conduct interesting, valuable research, but to also maintain a level of independence.  

“It was incredibly valuable. But more broadly, it’s so important that there is funding available for early career researchers to explore questions around sex and gender. It’s been so overlooked for so long.”

The President and CEO of Brain Canada, Viviane Poupon, hailed the work of both Dr. Lissaman and Dr. Clarke.

“Supporting innovative post-doctoral fellows is central to Brain Canada’s mission, because their curiosity and drive push the boundaries of brain science,” said Dr. Poupon.

“Dr. Clarke and Dr. Lissaman’s work underscores how critical it is to integrate sex and gender considerations into research, especially as we deepen our understanding of women’s brain health. By investing in studies like theirs, we’re helping to shape a future where Alzheimer’s can be identified earlier, and care becomes more precise and equitable for all.”

Source: Mind Over Matter 22