Diversity Matters
by Mind Over Matter V 13:
Update on Canada’s Largest Collaborative Research Into Neurodegenerative Diseases
Until recently, the scientific research community showed little interest or inclination in understanding why women are more likely to develop Alzheimer’s disease (AD) than men. Indeed, females (both human and non-human) have historically been excluded from clinical research and trials, in part due to the common belief that females were more “complicated” than males. However, both sex (biological attributes) and gender (sociocultural factors) affect our risk of developing certain diseases, how well we respond to medical treatments, and how often we seek health care.
Importantly, studying sex and gender differences is no longer an outlier, but rather has become an essential component in Canada’s largest research study of neurodegenerative diseases.
“There’s lots going on. In fact, sex and gender research is teeming with activity,” said Dr. Gillian Einstein, who holds the Wilfred and Joyce Posluns Chair in Women’s Brain Health and Aging, and is the lead of the Women, Sex, Gender and Dementia (WSGD) cross-
cutting program in the Canadian Consortium on Neurodegeneration in Aging (CCNA).
“I think the consciousness is really raised, and that’s exciting,” Dr. Einstein told Mind Over Matter®.
THE MANDATE OF THE WSGD CROSS-CUTTING PROGRAM IS TO ENSURE THAT EVERY CCNA RESEARCH PROJECT EXPLORES HOW AGING AND NEURODEGENERATIVE DISEASES AFFECT WOMEN AND MEN DIFFERENTLY, AND ENDEAVOURS TO LEARN MORE ABOUT THE UNDERLYING REASONS FOR THE DISPARITIES BETWEEN THE DIVERSE GENDERS.
As a dramatic measure of the progress, there were 20 publications from the CCNA group in 2020 that addressed sex and gender disparities in dementia, compared to 11 the previous year.
Across the breadth of different research projects, the scientists uniformly observed that the field had been neglected.
Dr. Nadia Gosselin found this to be the case in her studies of the relationship between sleep apnea and dementia.
“Because sleep apnea is more prevalent in men, all of the literature has been more focused on men than women. In fact, women tended to be excluded from the literature altogether,” said Dr. Gosselin, a neuropsychologist who is an Associate Professor of Psychology and Director of the Center for Advanced Research in Sleep Medicine.
Poor sleep has been identified as a risk factor for dementia. Dr. Gosselin’s research specifically examines the impact of sleep apnea, a disorder in which a person’s breathing pauses or becomes more shallow than normal during sleep. While younger men suffer from this disorder at a higher rate than women, this gender disparity disappears after menopause.
Notably, women with the disorder (unlike men) seem to exhibit changes in brain structure and a decline in cognition. Women also present different symptoms, and their doctors are therefore less likely to detect the disorder. While men are more likely to report the classic symptoms of sleep apnea, such as snoring and gasping, women tend to report atypical symptoms like difficulty falling asleep, night sweats, and morning headaches.
“Women are not well diagnosed, so they are more at risk than we thought,” said Dr. Gosselin.
She and her team are trying to learn more about the relationship between sleep apnea and dementia and, crucially, the differences between women and men. Through observations of research participants who suffer from the disorder, they will monitor oxygen saturation and measure the link with cognitive decline, hoping to determine whether women’s cognition declines faster than men.
“If we want to understand the role of poor sleep quality with dementia, we need to study the sexes separately,” Dr. Einstein noted.
“It will impact how we manage or diagnose dementia or conduct intervention programs,” added Dr. Gosselin. “If women are more at risk, we’ll need to be more aggressive in our interventions to prevent cognitive decline and dementia.”
For Dr. Teresa Liu-Ambrose, a better understanding of the differences between women and men could help inform an intervention that we can all benefit from for our brain health: exercise.
“THE REASON WHY SEX AND GENDER ARE CRITICAL IN THESE ASSESSMENTS IS THAT THERE IS EVIDENCE TO SUGGEST THAT OLDER FEMALES AND MALES RESPOND DIFFERENTLY TO EXERCISE TRAINING.”
Dr. Liu-Ambrose is a Professor in the Department of Physical Therapy at the University of British Columbia, and a Canada Research Chair in Physical Activity, Mobility, and Cognitive Health. She and her team have been leading older adults in the Vancouver area through monitored exercise programs and measuring their responses. Their findings to date suggest that aerobic exercise may provide greater brain benefits to women than men.
The researchers are exploring potential explanations for this occurrence, with a focus on BDNF or “brain-derived neurotrophic factors.” BDNF plays a key role in neuronal survival and growth, serves as a neurotransmitter modulator, and participates in neuronal plasticity, which is essential for learning and memory. Blood tests that were performed on the female participants revealed increased levels of BDNF after aerobic training.
“I’d call BDNF fertilizer for your brain or brain vitamins,” explained Dr. Liu-Ambrose. “Neurotrophic means literally growth of neurons, so these factors when they are released within the brain promote cell growth.”
She cautions that much more research is needed, particularly on the potential benefits of resistance training and how the impacts differ between women and men. The recommended forms of exercise may be different and should be targeted. “Exercise is helpful, but to have the maximum benefit for the individual, we need to know specifics.”
WHILE EXERCISE IS BELIEVED TO HAVE A POSITIVE IMPACT IN STAVING OFF DEMENTIA, HEARING LOSS HAS BEEN IDENTIFIED AS A RISK FACTOR.
A major report published in The Lancet in 2017 (with a 2020 follow-up) described hearing loss as the single largest risk factor for dementia that had the potential to be modified. In other words, if an individual takes action to cope with declining hearing, she or he may reduce the risks.
However, The Lancet report did not touch on the differences between women and men; rather, it was a review of the existing literature that did not account for sex and gender.
“It’s the same story as in many aspects of health – men’s problems are better understood and better dealt with,” said Dr. Kathy Pichora-Fuller, a Professor Emerita in the Department of Psychology at the University of Toronto.
She told Mind Over Matter® that individuals often delay getting treatment for hearing loss because they fear that wearing a hearing aid will make them look or feel old, which can lead to a cascade of negative effects. People who have difficulty hearing (or vision problems) may choose to withdraw from social activity rather than seek help.
“Social isolation and inactivity in socializing also isn’t good for your brain,” said Dr. Pichora-Fuller. “It’s good for your brain if you are active, socially active, mentally active, cognitively active. And sooner or later, if you’re inactive, then your brain can be under stimulated, it’s kind of a downward spiral.”
SEX AND GENDER COME INTO PLAY WITH THE TYPES OF SUPPORT THAT ARE AVAILABLE FOR INDIVIDUALS WITH HEARING LOSS.
According to Dr. Pichora-Fuller, men more frequently work in industries where noise is a known hazard and where union contracts and workers’ compensation programs provide access to hearing care, including hearing aids if needed.
“So, working in noise puts men on a fast track for developing hearing problems, but they can get help for occupational hearing loss and their wives tend to be very supportive. Conversely, hearing loss in women may not be picked up at work; their hearing problems frequently develop later in life and may not be identified or treated as early as hearing problems in men. Additionally, women tend to not receive much social support from their husbands when they do get help for hearing problems.”
Dr. Pichora-Fuller’s project is aimed at developing programs to challenge the stigma and negative attitudes associated with getting help for vision and hearing problems. “Our research will provide training about ageism and how to not fall prey to the negative stereotypes about hearing so that aging adults do not delay taking advantage of the treatments that are available and known to be effective.”
More broadly, she said that CCNA researchers are exploring sex and gender differences related to hearing and dementia, filling the gaps from past research that overlooked these critical differences.
WHETHER IT IS HEARING, SLEEP, OR EXERCISE, DR. EINSTEIN BELIEVES THAT THE GROWING RECOGNITION OF THE IMPORTANCE OF SEX AND GENDER CONSIDERATIONS IN AGING AND DEMENTIA RESEARCH IS HAVING A SIGNIFICANT IMPACT.
“It’s terrific! People see how important it is and are applying it to their own areas of expertise,” she said.
Dr. Einstein is also encouraged that new funding is on the way. A call recently went out for three new proposals, each of which would be eligible for $90,000 for sex and gender research, with funding from Women’s Brain Health Initiative, Brain Canada, and the Canadian Institutes of Health Research.
“I’m proud of the Women, Sex, Gender, and Dementia cross-cutting program. It’s got a life of its own, which is wonderful.”
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The Canadian Consortium on Neurodegeneration in Aging (CCNA) is a national initiative to foster broad collaboration and knowledge sharing among researchers who study neurodegenerative diseases that affect cognition in aging.
Based on their area of specialization, CCNA’s researchers are divided into 19 teams throughout Canada, and are working in the areas of prevention, treatment, and quality of life. They draw on the data of national platforms, and are supported by cross-cutting programs that assist teams in overarching aspects of research such as considerations of sex and gender.