The Canadian Consortium on Neurodegeneration in Aging (CCNA) is a national network that integrates multiple disciplines and approaches to dementia research.

The consortium catalyzes research on the conditions that bring about dementia, seeks new treatments, and explores ways to improve the quality of life of people living with dementia.

CCNA Phase III

Theme 1: Primary prevention

Multinational assessment of risk factors and vascular disease in elders with dementias using longitudinal cohort studies: The MARVEL Project

Principal Investigators: Amy T. Hsu, Andrew R. Frank, Ann-Marie Julien, Wallis Lau, Hao Luo and Davide Liborio Vetrano

The prevalence of multimorbidity increases with age. In Canada, about one-third of seniors have at least 2 of the 10 most common chronic diseases, including heart disease, stroke, cancer, asthma, chronic obstructive pulmonary disease (also known as COPD), diabetes, arthritis, dementia, mood and anxiety disorders. The prevalence of multimorbidity increases to 70 to 80% among seniors living with dementia. Specifically, people living with dementia are more likely to experience cardiovascular diseases, such as hypertension, diabetes, stroke, coronary artery disease, and congestive heart failure. Dementia and cardiovascular disease share several common risk factors. In addition to the numerous lifestyle-related modifiable risk factors (for example, smoking, physical inactivity, poor diet, etc.), several blood biomarkers (such as cholesterol level) might be predictive of stroke, post-stroke complications, cognitive decline, as well as dementia. A better understanding of these blood biomarkers and how they are related to the onset of cardiovascular diseases and cognitive decline could improve our understanding of how dementia develops and support earlier identification of both cardiovascular disease and dementia risk. In this project, we will use several large healthcare administrative databases and longitudinal cohort studies in Canada and abroad to comprehensively examine the parallel trajectories of changes in the concentration of these blood biomarkers, cardiovascular events, and cognitive decline over a person’s life course.

Perimenopause & exercise: moving for a stronger and resilient brain by the EPIC Team

Principal Investigators: Teresa Y. Liu-Ambrose, Cindy Barha, Liisa A. Galea and Lindsay S. Nagamatsu

Each year, millions of females around the world experience the menopause transition (i.e., perimenopause), when hormones levels change rapidly and cause many symptoms including hot flashes, weight gain, sleep problems, depression, anxiety, and brain fog. Importantly, perimenopause may increase the risk of dementia for females and contribute to the fact that 2/3 of those living with Alzheimer’s disease are females. Many perimenopausal females experience challenges with their thinking abilities that impact their capacity to work and function. Research also shows detrimental changes occur in the brains of perimenopausal females. Thus, perimenopausal females need strategies to bolster their brain health. What modifiable factors (e.g., sleep) are associated with poor thinking abilities in perimenopausal females is not well understood. The World Health Organization strongly recommends physical activity interventions to reduce the risk of decline in thinking abilities. However, whether exercise can specifically improve thinking abilities and brain health in perimenopausal females has not been examined. We also don’t know how exercise improves thinking abilities or if it could make the female brain more resilient in the longer term. Our research team aims to address these important knowledge gaps in female brain health. Our team will first identify modifiable factors that are related to thinking abilities among perimenopausal females. We will then study the effects of a 6-month exercise program on thinking abilities and brain health in 150 physically inactive perimenopausal females, aged 40 to 55 years, who are experiencing difficulties with their thinking abilities. We will also explore how exercise improves thinking abilities. Given the number of perimenopausal females globally, our proposed study could have major impact. Our research will also reduce the stigma that prevents perimenopausal females from seeking care and support for their brain health.

Effects of GLP1 agonist-induced weight loss on cerebral and blood markers of neurodegeneration in individuals with obesity and genetic risk for Alzheimer’s disease

Team Lead: Alain Dagher

Obesity in mid-life is a significant risk factor for dementia and Alzheimer’s disease. However until recently there were very few safe and effective weight loss treatments available. This situation has changed in the last few years with the advent of a class of medications called GLP1 receptor agonists. These medications were originally developed to treat diabetes however it was realized that they could also cause significant weight loss in people without diabetes. We plan to recruit 120 individuals with obesity and genetic risk for Alzeimer’s disease aged 30-55 and administer a medication called tirzepatide to them for one year. This is expected to cause a 15 to 20% loss in body weight and ameliorate metabolic measures. We will then use magnetic resonance imaging to see if weight loss is associated with concomitant changes in brain health. Participants will have extensive clinical evaluations. We will then be able to see if improvement in metabolism is associated with improvements in brain and cerebrovascular function and anatomy.

Theme 2: Secondary prevention and treatment

Developing novel brain imaging and blood testing against a major early driver for timing diagnosis and effective treatment of age-dependent tauopathies

Principal Investigators: Kun Ping Lu, Robert Bartha, Ting-Yim Lee, Guillaume Paré, Stephen H. Pasternak, and Xiao Zhen Zhou

Debilitating dementia is projected to affect 6 million Canadians and cost 3T CAD over the next 30 years. Alzheimer’s disease (AD) is the most common dementia, while traumatic brain injury (TBI) is one of the best-known risk factors. Despite dementia developing over decade, current diagnostic tools-like brain imaging for tangles, cerebrospinal fluid analysis, and blood tests-are delayed, invasive or prohibitively expensive, limiting their clinical uses. We’ve identified Pin1, a stress-responsive protein that protects the brain from AD and TBI by preventing the toxic transformation of tau into cis P-tau, which causes death of brain cells. Cis P-tau is a central early driver and biomarker of AD and TBI. We’ve also developed a unique antibody that captures and removes only cis P-tau, halting cell death and dementia progression in animal models, and it is also safe in human trials. While antibody treatments are costly and patient responses vary, no test currently exists to detect cis P-tau. Leveraging our discoveries and proprietary antibody, we have assembled a multidisciplinary team with the requisite expertise to pioneer early, non-invasive and cost-effective brain imaging and blood tests uniquely designed to detect cis P-tau in AD and TBI. 1) We will label our antibody with a safe, traceable substance so we can use brain scans to see and measure cis P-tau induction and antibody-mediated clearance in the brains of TBI and AD animals. 2) We will further improve our cis P-tau blood tests and figure out if its levels correlate with injury severity and treatment in TBI and AD animals and can spot early signs of dementia and predict outcomes in TBI and AD patients. Our studies will develop early, non-invasive and affordable brain imaging and blood tests against a key early driver of dementia. These innovations could transform patient risk identification, disease prediction, treatment selection, and monitoring-especially with the antibody already in clinical trials.

A novel approach to dementia prediction and prevention by integrating cognitive, mobility, and exercise interventions to combat neurodegeneration in aging

Principal Investigators: Manuel M. Montero Odasso, Cindy Barha, Robert Bartha, Sylvie N. Belleville, Jennifer M. Bethell, Louis Bherer, Michael J. Borrie, Amer M. Burhan,  J. Richard M. Camicioli, Jodi D. Edwards, Frederico P. Faria, Sarah A. Fraser, Karen Zown-Hua Li, Teresa Y. Liu-Ambrose, Laura E. Middleton and Maria N. Rajah

As people age, they may experience memory and movement changes that can increase their risk of dementia. Our team, the Mobility, Exercise, and Cognition (MEC) team, has spent a decade working to identify factors that help predict who might develop dementia. We focus on using motor skills, such as walking while talking, to create better, more accessible tools to help predict dementia, particularly for people with Mild Cognitive Impairment (MCI). MCI is a condition where memory problems go beyond normal aging, yet not everyone with MCI will develop dementia. Current prediction methods, like brain scans and genetic tests, are limited in accurately assessing dementia risk because they do not fully capture the role of physical and vascular health. However, we demonstrated that walking while completing a mental task-a measure called “dual-task gait”-is a powerful marker of brain health and future dementia risk. Our project has two main goals: to improve dementia risk prediction and to develop exercise and mental training guidelines to delay dementia. While research supports that exercise and mental training improve cognition, there are no clear, practical guidelines for Canadian healthcare providers on how to prescribe these interventions. With the help of individuals with lived experience and clinicians, we will develop patient-centered prediction tools and guidelines for exercise and mental training. Using data from two major studies, we will create a model that includes walking ability, cognitive tests, brain imaging, genetics, and vascular health to make more accurate predictions. Also, by identifying individuals most likely to benefit from exercise and mental training, we can target interventions to those at greatest risk. We expect these tools to help people maintain cognitive and physical health, potentially lowering dementia rates and healthcare costs, and providing healthcare providers with practical, research-backed guidelines to support brain health in aging.

Wearable sensing and stimulation of sleep physiological features related to resistance and resilience to dementia-associated brain changes

Principal Investigators: Andrew Lim and Thanh Dang-Vu

It is now clear that people who sleep well have a lower risk of dementia. Moreover, among people with dementia, it is a common experience a night of “good” sleep is often followed by a good day whereas a night of “bad” sleep is followed by a bad day. But what about a “good” night of sleep is most important to preventing dementia and supporting memory and concentration? Duration? Quality? Dreams? Depth? This is a key question as we now have the ability to improve not only sleep duration, but also sleep quality and depth, using gentle sound stimulation, lifestyle interventions like exercise, and new medications. In this study, we will use wearable technologies to allow older adults to measure their own sleep duration, quality, depth and other characteristics, and we will relate this to brain scan measures of dementia-associated brain changes and to thinking and concentration. We will identify what aspects of good sleep are most important to preventing dementia and supporting cognitive resilience in the face of dementia. Then we will use wearable headbands that play soft auditory tones to enhance these features, with an ultimate goal of preventing dementia in those who don’t yet have it, and promoting cognitive resilience in those who already do, so that every day is a “good” day.

Investigating cellular biomarkers of vascular white matter injury in neurodegeneration

Principal Investigators: Amanpreet Badhwar, Eric E. Smith and Shawn N. Whitehead

Vascular issues in the brain are major contributors to cognitive impairment and often co-occur with neurodegenerative diseases like Alzheimer’s. Research suggests that damage to the brain’s white matter (WM)-a network of nerve fibers connecting different brain regions-may link small blood vessel disease to cognitive decline. This damage, seen on brain scans as “white matter hyperintensities” (WMH), likely results from issues with vascular cells (e.g., endothelial), the blood-brain barrier, and brain immune cells (e.g., microglia). However, direct evidence of how these processes cause white matter damage in living individuals is still needed. New technologies now allow us to detect brain-specific markers in blood, helping with diagnosis, prediction, and treatment guidance. One promising source is tiny particles called extracellular vesicles (EVs), released by brain cells like blood vessel (endothelial) and immune (microglial) cells. These EVs carry proteins into the bloodstream that may reflect brain health. In this study, we aim to find blood markers linked to white matter damage and cognitive decline. By analyzing EVs from brain blood vessels and immune cells, we hope to discover markers that predict brain imaging-detected white matter damage, cognitive decline, and the risk of progressing from mild cognitive impairment to dementia. Our team combines expertise in neuroscience, biomarker development, and clinical research to analyze blood and brain imaging data from over 1500 participants in the pan-Canadian CCNA-COMPASS-ND study. This project aims to uncover new biomarkers and pathways that could lead to early diagnosis and treatment for vascular-related brain diseases. Our findings will contribute to the broader understanding of age-related cognitive decline and be shared with the research community to enhance efforts in prevention and intervention.

Theme 3: Quality of life

Strengths-based approaches to assessing and measuring cognitive impairment, dementia, and frailty in older First Nations people in Canada and Australia

Principal Investigators: Jennifer Walker and Dina LoGiudice

The overall goal of this collaborative project between First Nations in Canada and Australia is to understand frailty among older people, in the context of cognitive impairment, in ways that are grounded in First Nations and strengths-based perspectives, and informed by clinical understandings of frailty, cognition, and dementia. Culturally-grounded measures are important for First Nations’ self-determined organization of care for older people. However, existing measurements are rooted in deficit-based approaches, both in population research and in clinical assessment. To address this gap, we will build on previous First Nations-led research and established First Nation community priorities in both Canada and Australia to co-create strengths-based and culturally-informed 1) measures of frailty for use in population datasets, 2) clinical tools for individual assessment of frailty, and 3) community interventions for frailty for those with cognitive impairment. We will also determine the extent to which there are common contexts and approaches in First Nations in Canada and Australia. This research will have a substantive impact on strengths-based clinical practice and community programming to delay frailty and promote strengths in First Nations people who are experiencing cognitive impairment or dementia, and it will support international collaboration on First Nations dementia research.

Co-design, implementation, and evaluation of a trauma-informed care framework to enhance trauma-informed practices in long-term care

Team Leads: Kim A. Ritchie, Sophiya Benjamin and Margaret McKinnon

Trauma is common among older adults, with many experiencing at least one traumatic event in their lifetime, often leading to a number of psychological symptoms that reduce their quality of life. Moving to a long-term care home (LTCH) can add additional challenges for older adults who have experienced trauma, as the intensity of care can inadvertently re-traumatize them. The COVID-19 pandemic exacerbated feelings of vulnerability among LTCH residents who were socially isolated from family and friends for prolonged periods of time. However, trauma-informed care (TIC) practices-which emphasize safety, autonomy, and respect-can reduce these risks by providing an organizational framework and care practices which are sensitive to trauma. This study aims to co-design a TIC framework for LTCH to reduce trauma symptoms and increase quality of life among the LTCH residents. This project is expected to take place over four years. In the first phase, interviews and a survey will be conducted with residents, family/friend care partners, staff care partners, and leadership to learn more about their experiences and attitudes towards TIC. In the second phase, the TIC framework will be piloted in one LTC facility. In the third phase we will compare the impact of the TIC framework among residents in 4 LTC facilities. The fourth phase will involve widespread dissemination of the framework to other LTCHs across Canada. We anticipate that implementing TIC in LTC will reduce challenging symptoms, decrease potentially inappropriate medication use and improve quality of life for residents, along with contributing to improved workplaces for staff. This project will also produce a TIC framework and training resources which can be shared with LTC facilities across Canada, supporting other facilities to adopt trauma-sensitive practices.

Co-design of Indigenous dementia resources in Canada and AustraLia (CIRCLE): Enhancing health communication for Indigenous peoples along the dementia journey

Principal Investigators: Pamela Marie Roach and Kate Smith

Indigenous peoples are experiencing disproportionate rates of dementia due to ongoing colonization, yet culturally safe health communication to improve the dementia assessment process for Indigenous peoples remains under-resourced. Therefore, our proposed research aims to address this gap by co-designing culturally-centred resources to strengthen health communication for Indigenous people in Canada and Australia along the dementia assessment journey, specifically for risk reduction and cognitive assessment. Our research uses an Indigenous adaptation of participatory action research while ensuring Indigenous Ways of Knowing, Being, and Doing are woven throughout. Furthermore, our research will be informed by an ecological systems theory, providing a holistic lens for considering interconnectivity and relational interactions. First, we will collaboratively identify and map health communication pathway strengths and resource needs to inform community resource priorities for dementia risk reduction and cognitive assessment. This will be completed using yarning (Australia) and talking (Canada) circles with Elders and community members. Simultaneously, an international scoping review will be completed to determine what is available in the published and grey literature. In the second phase of the work yarning and talking circles will again be completed to co-design, develop, and translate community-prioritized, culturally-centered resources to strengthen health communication pathways for dementia risk reduction and cognitive assessment. The involvement of co-researchers and a participatory approach embeds integrated knowledge translation in the methodological approach. Moreover, this work and the ethical, strengths-based, and Indigenous-centered approach that adheres to ethical principles is highly applicable to other contexts and other underrepresented groups in dementia care settings by providing a process to undertake this developmental work.

Determining mechanisms of sensory-cognitive links in aging and dementia to inform interventions and public health: A multi-disciplinary team approach

Principal Investigators: Natalie A. Phillips, Amanpreet  Badhwar, Jennifer L. Campos, Britt I. Drogemoller, Ingrid Ekström, Raheleh Haji Gholam Saryazdi, Zahinoor Ismail,  Karen Zown-Hua Li, Paul Mick, Joseph B. Orange, Margaret K. Pichora-Fuller,  Marie Y. Savundranayagam and Walter Wittich

Sensory loss (hearing, vision, smell) is strongly associated with cognitive decline and dementia and is important for the quality of life and functional capacity of older adults with or at risk for dementia. Our national research team will conduct innovative research that will produce an integrated model of relationships between sensory health and cognitive outcomes and will lead to new knowledge with the potential to improve the quality of life of older adults. Our interdisciplinary team spans psychology, audiology, otolaryngology, low vision, genetics, gerontology, neurology, brain imaging, and epidemiology. Our research will test possible pathways linking sensory loss, cognitive decline, and dementia, in the general population and in persons living with dementia. We will investigate three possible reasons: a) common biological causes (e.g., genes), b) that sensory loss causes cognitive and/or brain changes due to poor quality sensory input, and c) that social, physical activity, and/or mental health changes due to sensory loss result in poorer outcomes. We will examine how sensory loss is related to activities important for maintaining the social participation of older adults, including a) effective communication between individuals living with dementia and their care partners, b) driving behaviours, and c) changes in mental health. We will examine potential differences between men and women. We will provide education on managing modifiable sensory risk factors for the public and health-care providers and we will provide interdisciplinary training for the next generation of dementia researchers. Our work is guided by collaboration with knowledge users and patient partners with lived experience with cognitive decline and/or sensory difficulties, who will contribute to the research design and the communication of relevant and effective knowledge. Together, this work has the potential to enhance approaches to personalized medicine and public health.

Advancing equity in dementia care in Canada: An intersectional and participatory approach

Principal Investigators: Claire Godard-Sebillotte, Howard Bergman, Ngozi F.  Iroanyah, Zahinoor Ismail, Sathya Karunananthan,  Kimberlyn M. McGrail and Isabelle Vedel

Canadians with dementia often face barriers to getting the care and support they need. These challenges can be even greater for those who are disadvantaged by factors like their gender, socioeconomic status (meaning education, income, and type of job), race, or the language they speak. When these factors overlap, they can create even larger obstacles to accessing services and living a good quality of life. Unfortunately, little research has focused on understanding “intersectionality”, or how these overlapping factors affect people living with dementia. Our team is working to address this gap. We have extensive experience in researching health services and equity, along with strong partnerships with health organizations, community groups serving people from equity-seeking groups, clinicians, and people living with dementia and their care partners. Building on this foundation, we will: 1) Create a list of national and provincial health databases that include information on social factors, and evaluate how useful they are for studying equity and intersectionality in dementia care, 2) Use this data to create provincial portraits for Quebec, Ontario, Alberta, and British Columbia, showing how gender, income, race, and language interact to influence the healthcare use and outcomes of people with dementia, and 3) Work with community organizations, clinicians, and people affected by dementia to identify and prioritize steps to improve care for those facing the greatest challenges. Through this team grant, we plan to uncover the unique challenges faced by people living with dementia from equity-seeking groups, identify ways to reduce health inequities, improve care and quality of life, and train the next generation of leaders in dementia equity research and practice.

Innovating driving assessment in adults with cognitive impairment: A person-centered approach leveraging artificial intelligence and digital technology

Principal Investigators: Sayeh Bayat, Gary Naglie and Mark J. Rapoport 

Deciding when someone with dementia should stop driving is a major challenge in dementia care. While dementia can impact driving safety, a diagnosis does not automatically mean someone must stop driving-many individuals in the early stages can continue to drive safely for some time. Currently, the most depended on way to assess driving safety is through on-road driving assessments at specialized driving assessment centres. These tests are often unavailable, expensive, and may not accurately represent everyday driving behaviour. Our research seeks to create better tools for assessing driving safety in people with memory and thinking challenges. To do this, first, we will collect real-world driving information using easily installed sensors in a person’s own car. This will allow us to analyze how driving behaviour varies among adults without memory and thinking issues, those with mild memory and thinking concerns, and individuals in the early stages of dementia. We will also monitor changes in driving over time to track how they change in relation to changes in memory and thinking. Additionally, we will explore whether walking tests that challenge both movement and thinking, which can be done in doctor’s offices, offer clues about driving skills. Finally, we will also study whether real-world driving information is consistent with information from existing tools that predict crash risks in older drivers. By building the largest collections of real-world driving information in individuals with varying levels of memory and thinking abilities, our goal is to develop a fair, available, and effective approach to assessing driving skills to support individuals with memory and thinking problems, their families and doctors in making informed decisions about driving safety.

 Promoting health equity among people living with dementia and care partners in ethno-racial communities: Co-designing quality of life supports

Principal Investigators; Laura E. Middleton, Pamela E. Baxter, Jennifer M. Bethell, Ngozi F. Iroanyah, Jasmine C. Mah, Carrie A. McAiney, Monica J. Parry, Mariko L. Sakamoto, Marie Y. Savundranayagam, Ingrid R. Waldron, Karen Lok Yi Wong and Marie-Lee Yous

The overarching aim of our team is to improve the quality of life of people living with dementia and care partners, with a focus on underserved communities. Identifying effective strategies to improve the quality of life of people living with dementia and care partners (i.e., caregivers) is a national priority. Need for supports is even greater among people living with dementia and care partners from ethno-racial communities who face additional challenges accessing supports and services including racism, language barriers, and differing cultural views and stigma of dementia. Within this 4-year grant, we will work with people living with dementia, care partners, and partner organizations from the Chinese, South Asian, and Black communities using a participatory approach towards the following objectives: 1.To understand what quality of life to people living with dementia and care partners from Black, Chinese, and South-Asian communities in Canada. We will also identify barriers to quality of life and the supports needed. 2.To co-design supports for quality of life of people living with dementia and care partners in the communities of interest. 3.To share our findings with interested groups, including people living with dementia, care partners, community organizations, and policy makers. 4.To build the knowledge and skills of researchers, trainees, people living with dementia, care partners, and community organizations to engage in dementia research, especially with ethno-cultural communities. The impacts of our work include: (i) new, ready-to-be-tested interventions that aim to support positive quality of life in the Chinese, South Asian, and Black communities, and (ii) researchers and trainees with increased knowledge of dementia and skills to engage in dementia research, building capacity to address the challenges of dementia.

Improving the quality of life of older adults living with neurodegenerative diseases by studying the scaling up of tools that support care transitions within French-speaking communities in Canada

Principal Investigators: Patrick Archambault, Lise Bjerre, Stéphanie Collin, Danielle L. De Moissac and France Légaré

This research project aims to improve the way we care for older adults living with neurodegenerative diseases (e.g., Alzheimer’s disease) when they experience care transitions between different points of service in the health care system, for example, when they return home after hospitalization. We will focus on Francophone minority communities, which are particularly vulnerable to poorly planned care transitions due to language barriers. These dysfunctional transitions negatively impact the quality of life of older adults living with neurodegenerative disorders and their caregivers. To remedy this situation, our research team aims to: 1- Identify best practices that help older adults with neurodegenerative diseases and their caregivers transition between different care settings. We will examine what works well in the literature and find ways to adapt these methods to the Canadian context. 2- Create indicators to measure the effectiveness of these transitions. 3- Work with patient partners, caregiver partners, and healthcare providers in Francophone communities across Canada to implement the best practices identified. We will offer training and support tailored to their context to help healthcare teams provide the best possible care to older adults living with neurodegenerative diseases and their caregivers. 4- Study how to make these improvements sustainable and accessible to all Francophone communities in Canada. In summary, this project aims to improve the quality of life of older adults living with neurodegenerative diseases and their caregivers by ensuring that they receive the best possible care as they navigate the healthcare system in Canada.

Canadian dementia health system performance team

Principal Investigators: Susan E. Bronskill, Aaron T. Jones, Julia Kirkham, Julie G. Kosteniuk, Colleen J. Maxwell and Dallas P. Seitz

Close to 733,000 Canadians live with dementia and many more people living with dementia will require care in the future. Currently Canada’s health system struggles to provide high-quality care for people living with dementia. For example, people find it takes a long time to see family physicians and specialists, and home care services can be inconsistent. If we could compare and report on the quality of dementia health services within and across provinces, it would help to identify gaps in care and improve quality of life of people living with dementia and their care partners. Starting with Alberta, Saskatchewan, and Ontario, we will build a team to conduct needed research on the dementia health system in priority areas for people living with dementia and their care partners. We will do this by analyzing health encounter data (also known as health administrative data) which is routinely collected across all provinces as part of care delivery. We will be able to analyze data on every person living with dementia in each province. We will also measure the quality of dementia health care services across provinces and share our findings publicly. Over the four years of the grant, we will grow our team to include additional provinces and territories. Through our team we will also train the next generation of researchers, build and strengthen ties to national and international research teams, and incorporate the perspective of people living with dementia and their care partners, health care providers, policymakers, and other groups. Our overall goal is to improve the quality of life for people living with dementia with timely evidence to support care planning for Canadians and their families.

Thank you to all of our partners!

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