Latest funding results of the Alzheimer Society Research Program

Care

Care

Sadaf Murad Kassam, University of Alberta 

Title: Exploring the Hospitalization Experiences of Ethno-Racial Older Adults Living with Dementia and their Care Partners in Arab and South Asian Communities.

Award/Grant: Doctoral Award

Ethno-Racial communities often face various challenges in accessing equitable healthcare services. Discrimination and racism in healthcare practices towards ethno-racial individuals, especially older adults with dementia, create barriers for them and their caregivers in accessing culturally sensitive care. Dementia in ethno-racial communities is considered taboo and stigmatized, with these groups often avoiding hospitalization until it is life-threatening. Currently, no studies in Canada target South Asian or Arab communities and the hospitalization experiences of those living with dementia.

My research aims to address this gap by exploring the hospitalization experiences of older adults from these communities with dementia, along with their caregivers and healthcare providers. The findings will inform culturally inclusive dementia care in hospitals, catering to the diverse needs of older adults with dementia. By allowing ethno-racial communities to share their hospitalization experiences, this research seeks to promote inclusivity and facilitate necessary changes in healthcare practices.

André Smith, University of Victoria

Co-funded with Brain Canada Foundation 

Title: A critical examination of family caregivers’ views on and experiences with medical assistance in dying. 

Award/Grant: Proof of Concept Grant

This study aims to understand the decision-making journey of families who support a loved one with dementia who is seeking medical assistance in dying (MAID). Legalized in Canada in June 2016, MAID allows eligible persons to end their lives through the administration of medication by a physician or nurse practitioner or through self-administration of medication prescribed by a physician or nurse practitioner. A 2021 amendment allows advance consent for MAID for persons whose natural death is reasonably foreseeable but who loses capacity for consent prior to MAID being provided.

The study specifically examines whether concerns over family caregivers’ stress and unmet needs for support, along with worries over inequities in long-term care for persons living with dementia play a role in the MAID decision-making process.

Juanita-Dawne Bacsu, Thompson Rivers University 

Co-funded with CIHR-IA

Title: Improving rural cognitive healthcare through lived experience: Care priorities, programs, and service needs.

Award/Grant: New Investigator Grant

Age is an important risk factor for cognitive impairment and dementia, and the number of rural older adults is growing. Rural older adults often face unique challenges to accessing cognitive healthcare compounded by limited public transportation, finances, specialist services, and stigma of dementia. Using interviews and group discussions, this study aims to enhance rural cognitive healthcare by identifying the care priorities, programming, and service needs of rural older adults living with cognitive impairment and dementia. Findings from this study will have the potential to inform policy, practice, and programs to support rural older adults living with cognitive impairment and dementia.

Oi Yee Wong, University of British Columbia  

Title: Co-creating culturally relevant virtual reality programs with community-dwelling older adults living with dementia: A patient-oriented research.

Award/Grant: Doctoral Award  

Virtual reality (VR) has shown the potential to improve the quality of life of people living with dementia. However, existing studies often overlook individuals residing in the community and VR's cultural relevance. My study aims to address the gaps by co-creating culturally relevant VR experiences with people living with dementia and their care partners in the community. The study will explore the impact of co-creating VR programs on people living with dementia and their care partners from diverse cultural groups and identify enablers and barriers to a meaningful co-creation process. Through four sessions, participants will collaboratively plan, film, and edit VR videos based on their cultural backgrounds and preferences and share experiences in subsequent interviews.

The study will develop a multilingual toolkit and a documentary to promote community-based VR co-creation initiatives. The collaboration with people with dementia in the study can support equity and inclusion in dementia research.

Aaron Jones, McMaster University  

Title: Geriatric emergency care among people living with dementia in Ontario. 

Award/Grant: New Investigator Grant

People with dementia in Canada frequently visit the emergency room (ER). However, emergency care is not designed with the needs of people with dementia in mind. Individuals with dementia face greater risks in the ER than other adults, including developing delirium, falling, or being admitted to hospital. Geriatric Emergency Medicine (GEM) programs are specialized nurse-led programs that are designed to provide comprehensive, holistic, and person-centered care in the ER for individuals living with dementia.

We will create a detailed picture of the care people living with dementia receive in the ED. This will enable us to identify gaps in care and find areas for improvements. We will also describe how accessible GEM programs are to people living with dementia. Finally, we will produce evidence on how well GEM programs improve outcomes for people with dementia. This evidence will directly inform strategy to expand geriatric emergency programs in Canada.

Arlene Astell, University of Toronto 

Co-funded with Brain Canada Foundation

Title: Boosting self-cueing to maintain independence in dementia.

Award/Grant: Proof of Concept Grant  

Everyday activities such as cooking often become difficult for people living with dementia. We have found that they can still do the physical bits, such as filling a kettle or peeling a potato. The problem is with the cognitive ‘glue’ that sticks the physical steps together. Research has shown that self-cueing can help children finish tasks. Self-cueing can also help people with aphasia communicate. Boosting self-cueing could help people living with dementia continue everyday tasks.

Gelareh Hajian, University of Toronto  

Title: On the Road to Sustained Mobility: Adapting Automated Vehicles for Older Adults with Dementia.

Award/Grant: Postdoctoral Award

Driving cessation significantly affects individuals with cognitive impairments, such as dementia, leading to further cognitive decline, reduced independence, and negative health impacts. Conditionally Automated Vehicles (CAVs), an emerging AV technology, offer a promising solution for supporting people with dementia (PWD) by handling most driving tasks, potentially delaying the need for complete driving cessation and maintaining safe driving practices. CAVs provide enhanced safety features over conventional vehicles, yet they require human intervention at their operational limits, necessitating situational awareness and fast reaction times, capabilities that may be compromised in PWD.

This research focuses on adapting CAVs to better meet the needs of PWD by enhancing the safety and efficacy of these vehicles. Through the development of tailored design solutions that include an effective multimodal warning system and robust monitoring strategies, the study aims to prolong mobility and independence for this demographic, ease caregiver burden, and improve quality of life without compromising road safety.

Grace Liu, University of Waterloo & Schlegel-UW Research Institute for Aging  

Title: Co-development of clinical practice guidelines to promote physical activity and quality of life for residents with dementia.

Award/Grant: Postdoctoral Award

The International Association of Gerontology and Geriatrics Taskforce recommends physical activity for older adults in Long-Term Care as there are broad benefits to cognition, function, and daily life. However, the recommendations do not provide much direction on what and how to implement practice/policy changes. The lack of guidance for physical activity may lead to inconsistent/ineffective programming. Since residents with dementia likely receive less programming, guideline development is essential to facilitate consistent, equitable and high-quality care.

Susan Bronskill, Sunnybrook Research Institute

Co-funded with Brain Canada Foundation 

Title: Health system implications of novel therapeutics for Alzheimer’s Disease: Supporting capacity planning with real-world evidence.

Award/Grant: Proof of Concept Grant

Many Canadians live with Alzheimer’s disease. Few treatments exist, but new drug therapies may slow the disease and prevent it from getting worse. Once researchers show that these drugs are safe and helpful, Canada will need to figure out how to make them available in a fair way. Does our health-care system have enough resources to support future demand? Our study asks how large this resource gap might be and investigates what other information Ontario needs to plan for dementia care. We will collect preferences for new therapies and dementia care pathways from: people with lived experience, healthcare providers,& policymakers. We will combine this information with data on actual health-care system use by Ontarians to develop possible options that include access to new therapies.

Manon Spigarelli, Laval University 

Title: Effects of repetitive transcranial magnetic stimulation (rTMS) on people with post-stroke aphasia asked to name the actions shown in a set of videos.

Award/Grant: Doctoral Award

Neurocognitive disorders have a significant impact, affecting many people each year. One of the most troubling effects is anomia, where individuals struggle to find the right words to name objects, and actions. This can severely hinder communication and social engagement. The study aims to assess how a combination of non-invasive brain stimulation and speech therapy can improve the ability of people with neurocognitive disorders to name actions accurately.

The study will include 40 participants with neurocognitive disorders, divided into two groups. Group A will receive brain stimulation along with speech therapy focused on action verbs. Group B will receive brain stimulation with placebo speech therapy. Participants will be evaluated before and after the intervention to measure improvements. This research aims to improve communication and quality of life for people with neurocognitive disorders. The results could also guide the development of new rehabilitation protocols that use brain stimulation and speech therapy.

Andrew McLennan, University of Regina

Co-funded with Saskatchewan Health Research Foundation

Title: Evaluation of Observational Pain Assessment Tools in a Sample of Older Adults with Severe Dementia in Collaboration with Caregivers.

Award/Grant: Doctoral Award

Unassessed pain can cause severe health problems, reduced quality of life, and even death for older adults with dementia. The American Geriatric Society (AGS) recommends that a pain assessment for older adults with severe dementia should include the use of an observational tool and input from informal caregivers. Most observational pain tools have not undergone sufficient psychometric testing and that could improve their ability to detect pain.

The purpose of this study is to conduct a rigorous psychometric evaluation of some of the best performing observational pain tools for older adults with dementia in collaboration with local caregivers in an urban Canadian setting. Local caregivers will work with the research team to provide their insight on matters of pain identification and knowledge translation. My goal is to take a collaborative approach to improving the accuracy of observational pain tools with the hope that it can reduce suffering and potentially save lives.

Elin Karlsson, Western University  

Title: Optimizing health in people with a dual diagnosis of hearing loss and cognitive impairment through the validation and preliminary implementation of a novel person-centred assessment of hearing in everyday functioning.

Award/Grant: Postdoctoral Award

One-third of adults over 65 experience hearing loss, making it the third most prevalent chronic health condition in older adults. Social isolation, depression, and increased dementia risk are often consequences of hearing loss. Hearing loss and dementia are highly associated, and research indicates that untreated hearing loss is a risk factor for early dementia onset. There is often a 10-year delay in seeking help for hearing loss, and an under-identification in primary care settings contributes to this delay. This may increase the risk of dementia and worsen health outcomes.

The project aims to help develop tools for detecting hearing loss and its impacts at an early stage and facilitate meaningful intervention. The project consists of two parts, the first to validate the Hearing and Functioning in Everyday life Questionnaire (HFEQ) for older adults with and without cognitive decline and secondly, to implement the HFEQ within primary care and evaluate the implementation.

Yu Qing (Jenny) Huang, University of Toronto 

Title: An evaluation of dementia risk, effective cognitive interventions and their intersection with social determinants of health in older adults with traumatic brain injury.

Award/Grant: Doctoral Award

Every year, more than one in five older adults in Canada experience a fall, which can lead to a traumatic brain injury (TBI). While older adults with TBI are at risk of dementia, we do not know the magnitude of such risk. We also need information about interventions to address their care needs, such as cognitive interventions, community or long-term care support, especially if they are at risk of health disparities because of social determinants (SDoH). I will conduct three projects focused on older adults with TBI: (1) investigating the risk of dementia and use of health services such as home care and long-term care admission among older adults with TBI, (2) describing the impact of cognitive interventions for older adults with TBI, (3) identifying which cognitive intervention is cost-effective for our healthcare system. I will use a health equity lens to identify interventions that reduce health disparities.

Cause

Cause

Valerie Sim, University of Alberta

Co-funded with Brain Canada Foundation 

Title: Amyloid beta oligomers: refining the therapeutic target through photolabeling and fractionation.

Award/Grant: Proof of Concept Grant

Alzheimer's disease is caused by clumps of misfolded brain proteins. Antibody treatments can remove some of these clumps but don’t cure the disease. Why? We believe they target the wrong clumps. Many proteins form different sized clumps in the brain during dementia, but only some cause disease. Unfortunately, methods for purifying these protein clumps can alter their structure, making it impossible to know what the clumps looked like before purification. We will avoid this problem by first photolabeling the brain.

This method coats all the exposed surfaces of the clumps, like tie-dye. Then we can purify all the clumps and figure out what the original clumps looked like, based on which surfaces are coated, like reassembling a jigsaw puzzle. By capturing the full range of clumps in the brain, we may find more relevant protein targets for the creation of more effective therapies with fewer side effects.

Andrew Snow, University of British Columbia  

Title: Investigating the role of amyloid precursor protein signalling in synapse formation and function.

Award/Grant: Doctoral Award

One of the strongest correlations with cognitive decline affecting people with Alzheimer’s disease is the loss of functional connections in the nervous system called synapses. The Amyloid Precursor Protein (APP) is linked to Alzheimer’s disease and is known to play a role in the formation and function of synapses. However, how APP is involved in these processes remains unclear.
This study uses a simple model organism to examine how APP functions as a signalling molecule to affect synapses. It explores when and where APP signalling is active in the nervous system and analyzes the developmental and functional consequences of manipulating APP signalling activity. This research will contribute to our understanding of the role of APP in the nervous system and how it is connected to synapse formation and function. It will lay a foundation for future research using more complex models to understand what drives synapse loss in Alzheimer’s disease.

Mark Cembrowski, University of British Columbia

Co-funded with Brain Canada Foundation

Title: A "tipping point" neuron type driving Alzheimer's Disease progression.

Award/Grant: New Investigator Grant

Alzheimer's disease (AD) is characterized by progressive cognitive impairments and accumulation of amyloid B ("AB") in the brain, with early AD associated with the onset of AB depositions in a brain region termed the hippocampus. In recent unpublished research from our laboratory, we have discovered an atypical excitatory neuron type in the hippocampus that seems well poised to play a pivotal "tipping point" role in early Alzheimer's disease.
In our research program, we are examining this cell type in a mouse model of AD. We will record activity of these neurons across AD progression and assess how these cells change their activity in cognitive decline, as well as how they deposit AB across the brain. We will also disrupt the activity of these neurons, seeking to slow AB depositions and cognitive impairments. In collection, we hope our work may ultimately help to inform new drug interventions to slow AD.

Jillian Stobart, University of Manitoba

Co-funded with Research Manitoba  

Title: Reducing astrocyte P2Y1 receptor signaling to slow Alzheimer's Disease progression.

Award/Grant: New Investigator Grant

Astrocytes, a type of brain glial cell, are important for brain function. During Alzheimer’s Disease (AD), astrocytes become abnormal. This may cause cell death and damage that contributes to the memory loss and sensory problems experienced by patients. This study will investigate the P2Y1 receptor on astrocytes because it increases during AD. We believe that higher amounts of the P2Y1 receptor causes astrocytes to damage other brain cells during AD. We will genetically reduce astrocyte P2Y1 receptors in mouse models of AD. We expect that more brain cells will survive and that the brain will function better when these receptors are reduced. This will also lead to less memory problems in AD mice. These results will help us better understand the causes of brain damage in AD. This will also lead to the future development of astrocyte P2Y1 receptor blocker drugs that slow disease progression.

Anthony Flamier, University of Montréal

Co-funded with Brain Canada Foundation

Title: The role of TMEM106B in Alzheimer's disease pathophysiology.

Award/Grant: Proof of Concept Grant

This project investigates the role of the TMEM106B protein in Alzheimer's disease (AD). Alzheimer's, a leading cause of dementia, is characterized by the accumulation of amyloid proteins that disrupt brain function. Our research focuses on TMEM106B, a protein involved in cellular transport, which we believe could help break down these harmful amyloid accumulations. Preliminary data suggest that modifying the expression of TMEM106B in brain cells could enhance their ability to clear amyloid, potentially slowing or reversing AD progression.

Through sophisticated genetic editing techniques and advanced imaging, this study aims to understand how TMEM106B interacts with amyloid proteins and assess its potential as a target for future therapies. Our findings could offer new insights into Alzheimer's treatment, highlighting the importance of TMEM106B in maintaining brain health.

Jonas Licea, University of Montréal / CHU Sainte-Justine Research Centre   

Title: Bri2, APP and glycoprotein M: A surprising molecular interaction linking Alzheimer's disease and herpes simplex virus type 1.

Award/Grant: Doctoral Award

Alzheimer’s disease and other dementias are complex conditions, and we’re still working to understand their exact causes. In Alzheimer’s, one important factor is the buildup of amyloid plaques in the brain. These plaques form when the APP protein isn’t processed correctly. Recent research suggests that a common virus, herpes simplex type 1, may favour plaque formation. In our previous work, we found that a protein from this virus (glycoprotein M) can interact with a human protein that helps protect against plaque buildup (Bri2). We’re now studying this interaction in more detail to see how it affects plaque formation in brain cells. We’re looking at how the levels and behaviour of different proteins change, which could give us new insights into how to prevent or treat Alzheimer’s. Our hope is that this research will lead to new strategies for tackling Alzheimer’s disease and improving the lives of those living with it.

Lisa Munter, McGill University

Co-funded with Brain Canada Foundation

Title: Genes involved in APP-mediated GLUT1 regulation.

Award/Grant: Proof of Concept Grant

Alzheimer’s disease is the most common form of dementia. The brains of many of the patients are less well supplied with glucose (sugar), but not much research aims to understand why this happens. Further, there is one specific protein of central importance to Alzheimer’s disease is amyloid precursor protein (APP). My lab found that there may be a connection between APP and the glucose supply to the brain, which is novel and has not yet been reported or investigated.

In this project, we will learn how exactly APP and the glucose supply to the brain are connected. Our project will use research models that lack the protein APP, which is not a standard procedure in Alzheimer’s disease research but is necessary for us to understand the connection between APP and the glucose transporter.

Maria Vera Ugalde, McGill University

Co-funded with CIHR-IA   

Title: Deciphering the molecular events weakening neuronal connections in Alzheimer's disease

Award/Grant: New Investigator Grant

A common characteristic of Alzheimer’s and other dementias is their progressive nature and lack of treatment. Even when the disease is diagnosed at the very early stages, we cannot slow down or stop neurons from losing their connections. The more connections lost the more advanced the cognitive impairment. Results from our project provide the opportunity to understand the etiology of neuronal connection loss and strengthen them to slow disease advance and preserve cognition.

Diagnosis

Diagnosis

Laura Fitzgibbon-Collins, Lawson Health Research Institute

Title: Longitudinal association of low cerebral blood flow during upright posture and cognition in adults with cognitive impairment.

Award/Grant: Postdoctoral Award

Most research characterizing brain blood flow in people with dementia has been done while lying down which may not capture the whole picture. I have developed a novel protocol to measure brain blood flow while standing and during walking which has revealed a unique relationship between higher brain blood flow and better memory only observed while upright. I will explore if my established non-invasive approach to detect changes in brain blood flow is linked to faster declines in thinking and memory. This will allow clinicians to have earlier, more affordable, and non-invasive warning signs, and therefore implement treatment faster and to a larger portion of people living in Canada. My goal is to improve the detection of memory impairments earlier than is currently possible, which can lead to better health outcomes for adults with dementia.

AmanPreet Badhwar, IUGM Research Center

Co-funded with Brain Canada Foundation 

Title: Establishing protein signatures of MRI-detected vascular brain injury in circulating endothelial-derived extracellular vesicles in Alzheimer’s disease.

Award/Grant: Proof of Concept Grant

Damage to blood vessels in the brain (cerebrovasculature) is frequently present in Alzheimer’s disease and worsens clinical symptoms. The goal of our project is to identify biomarkers of cerebrovascular damage in Alzheimer’s disease that can be measured in blood, which presently are not available. Our approach will be to analyze packets of material in “endothelial-secreted-extracellular-vesicles” (EEVs), especially those released by the cerebrovasculature into blood, and can be isolated using special techniques. Blood biomarkers, once identified and established, can serve as (1) a cost-effective, widely accessible tool in the evaluation of Alzheimer disease, and help orient other tests (e.g., neuroimaging) that are less accessible, and (2) aid in the prediction and monitoring of therapeutic effects of drugs.

Maxime Montembeault, Douglas Research Centre

Co-funded with Brain Canada Foundation

Title: Novel digital and adaptive marker of word-finding difficulties for early detection of Alzheimer’s disease.

Award/Grant: New Investigator Grant

Over 64% of older adults without neurocognitive disorders report forgetting the names of objects when speaking. These difficulties are commonly dismissed as typical aspects of the normal aging process. However, recent findings suggest that when these word-finding difficulties reach a certain level, they can serve as an indicator of Alzheimer's disease. Regrettably, current word-finding clinical tests are likely not sensitive enough to identify impairments in the general population. The study focuses on three key questions:

1) Do the existing word-finding tests reflect the experiences of older adults and can they predict Alzheimer's disease?

2) Can we improve word-finding tests by leveraging recent technological advancements and make a new test accessible to Canadian clinicians/researchers?

3) Is this novel word-finding test a more effective tool for detecting Alzheimer's disease? This project could have significant implications in the detection and diagnosis of neurocognitive disorders in older adults.

Darrell Mousseau, University of Saskatchewan

Co-funded with Saskatchewan Health Research Foundation

  

Title: Using patient-derived brain organoids to support a diagnosis of sporadic, late-onset Alzheimer disease.

Award/Grant: Proof of Concept Grant

Late-onset Alzheimer disease (LOAD; symptoms emerge after age 65) accounts for the vast majority of cases of AD but remains difficult to diagnose. LOAD is influenced by sex and environment and is highly variable in age-at-onset, clinical presentation, and rate of progression of neuropathological marker. There is a critical need for a tool that can accurately diagnose LOAD, regardless of patient-to-patient variability.
We developed a protocol that can generate human brain organoids― ‘brains-in-a-dish’―from a blood sample.

In a preliminary test, we were able to detect markers of pathology that confirmed a diagnosis of LOAD in a female donor. We will test more patient-donors to demonstrate the broader impact of our technology. We will also test whether we can identify any drug treatment that could delay the expression of these markers of pathology. Having a tool that combines diagnostic and therapeutic capabilities and overcomes any patient-to-patient variability is unprecedented for LOAD.

Joanne Matsubara, University of British Columbia

Co-funded with Brain Canada Foundation  

Title: MicroRNA biomarkers: Using Tears to Assess Alzheimer’s Disease.

Award/Grant: Proof of Concept Grant

Alzheimer's disease (AD) is a serious brain disease that gets worse over time. It's hard to diagnose early because the tests can be expensive or uncomfortable. Finding it early is important because new treatments are being developed quickly. These future new treatments may help to slow down how quickly the disease gets worse, and this will benefit those who know they are in the early stages of AD.
MicroRNAs (miRNAs) are tiny pieces of genetic material. They don't make proteins but control how proteins are made. In people with diseases, these miRNAs often change. Since they're found in many body fluids, we expect to see them in tear fluids of the eye. This research on tear fluids may help us detect Alzheimer’s disease.
We want to create an easy way to detect Alzheimer's disease early by analysing the tear fluids of the eye. Finding specific signs of Alzheimer's in tear fluids could help us identify the disease in a simple and accessible way in clinics.

Epidemiology

Epidemiology

Brittany Intzandt, Sunnybrook Research Institute

Title: Unraveling Dementia: Mapping Sex-Specific Risk Factors for Dementias Utilizing Network Analysis.

Award/Grant: Postdoctoral Award

During aging, Alzheimer's disease (AD) and vascular dementia (VaD) risk significantly increase. It is important to identify risk factors associated with AD and VaD, to target their prevention and thereby reduce likelihood of both. Sex influences risk factors that lead to development of AD and VaD, however, it is unknown the specific factors that enhance risk for each sex separately, and if certain risk factors are more likely to affect one sex more.

Risk

Risk

Arthur Cassa Macedo, McGill University

Title: The relationship between vascular risk factors and the clinical and pathological progression of Alzheimer's disease.

Award/Grant: Doctoral Award

Vascular risk factors (VRF), such as high blood pressure and high cholesterol, are health issues that can be changed or controlled and are known to increase the risk of Alzheimer's disease (AD) dementia. However, it is not clear if these conditions increase the risk of AD by directly causing the accumulation of proteins related to AD in the brain or by causing cognitive decline in other ways. Our study aims to find out if these VRFs predict the progression of Alzheimer's-related changes in the brain and cognitive decline. We will conduct a study with people who have no cognitive impairments, those with mild cognitive impairment, and those with Alzheimer's disease dementia. We will use a dementia risk score, which includes factors like age, sex, education level, blood pressure, body mass index, cholesterol levels, physical activity, and genetic risk factors, to assess each participant. We will then see if this score is linked to the progression of Alzheimer's-related changes in the brain, such as the buildup of amyloid-β and tau proteins, brain cell loss, and overall cognitive decline over 1 to 3 years. Understanding how these risk factors contribute to Alzheimer's could help develop better treatments.

Beatriz Oliveira, CIUSSS-NIM Research Center

Title: Investigating Sleep Disturbances, Genetic Susceptibility, and Cognitive Function in the Context of preclinical Alzheimer's Disease.

Award/Grant: Doctoral Award

Sleep problems have been found to worsen the risk of Alzheimer's disease, affecting memory and cognition. Our study aims to investigate the intricate relationship between Alzheimer's and sleep issues, specifically looking into whether genetic predisposition to Alzheimer's impacts sleep quality and if sleep problems worsen cognitive decline in at-risk individuals. We will be examining older adults who are at risk for Alzheimer's, including those with and without mild cognitive impairment, and assessing their sleep habits, genes, and cognitive function. By deciphering these connections, we hope to identify early indicators of Alzheimer's disease risk, which will enable us to provide targeted interventions to improve sleep and mitigate cognitive decline. This research offers hope for personalized approaches to Alzheimer’s prevention and treatment, benefiting individuals with dementia and their caregivers by enhancing understanding and support.

Therapy

Therapy

Philip Gerretsen, Centre for Addictions and Mental Health / University of Toronto

Co-funded with Brain Canada Foundation

Title: Does psilocybin increase synaptic density in the brain in patients with mild cognitive impairment?

Award/Grant: Proof of Concept Grant

Amnestic mild cognitive impairment (aMCI) is characterized by memory impairment that does not interfere with daily living. aMCI is viewed as a precursor to Alzheimer’s Dementia (AD), for which there are no known treatments. There is renewed interest in using psychedelics, including psilocybin, to treat mental illness. Evidence suggests that psilocybin exerts its psychedelic, and possibly its clinical effects, through interactions with a specific serotonin receptor in the brain, 5HT2A-R. Reduced 5HT2A-R density in the brain is associated with cognitive impairment (e.g., memory impairment). Preclinical animal studies suggest psilocybin may promote the formation of cellular connections in brain regions responsible for learning and memory, possibly through stimulation of 5HT2A-R. As such, psilocybin is worth exploring as a novel therapeutic for aMCI to counter neurodegenerative disease progression.

This study will use a double-blind-placebo controlled design to assess whether psilocybin increases the density of cellular connections in individuals with aMCI. Synaptic density will be measured in the brain using a type of medical imaging called positron emission tomography before and after psilocybin administration. We also aim to explore if changes in synaptic density are associated with improvements in memory.

Nishat Malik, Douglas Mental Health University Institute  

Title: Impact of pre-plaque CBD treatment on rescuing the hippocampal hyperactivity and cognitive impairment of a mouse model for Alzheimer's disease.

Award/Grant: Doctoral Award

Hyperactive cells in the hippocampus, a brain region for memory formation, can be found in early stage of Alzheimer’s disease (AD) before amyloid plaque formation, have been associated with memory loss. Reducing neuronal hyperactivity could be an early intervention approach for treating AD. Cannabidiol (CBD) is a non-intoxicating component of cannabis that has been used to reduce seizures. CBD may be promising for treating AD by reducing neuronal hyperactivity. My project aims to assess whether CBD can ameliorate the hyperactivity of hippocampal neurons and improve memory in a mouse model of AD. Neuronal activity (electrophysiology) will be assessed on brain slices before, during and after CBD treatment. Furthermore, with the implantation of lens, neuronal activity (miniscope recording) and mice behaviour will be recorded in freely moving mice during memory tasks, before, during and after CBD treatment. CBD is anticipated to rescue memory deficits in a AD mouse model by ameliorating hippocampal hyperactivity.

Robert Britton, Simon Fraser University

Title: Novel nucleotides for next-generation antisense oligonucleotides aimed at Alzheimer’s disease.

Award/Grant: Proof of Concept Grant  

Antisense oligonucleotides (ASOs) are a promising type of drug for neurodegenerative diseases, including Alzheimer’s disease. That the current generation of ASOs for Alzheimer’s disease have not performed well in the clinic is partially due to the fact that they are not reaching the brain areas most affected by Alzheimer’s. Our project will introduce new structures to ASOs that will alter the way they are distributed throughout the brain and allow them to reach the areas of the brain where they can make the most impact in slowing down or halting the progress of this disease.

Samantha Carew, Memorial University of Newfoundland and Labrador  

Title: A fresh perspective on glutamate balance could preserve synapses and cognition in Alzheimer's disease.

Award/Grant: Postdoctoral Award

Synapses are specialized connections that allow brain cells (neurons) to communicate. The strongest predictor of cognitive impairment in Alzheimer’s disease is the severity of synapse loss or damage. Glutamate is an essential molecule for this communication, but too much or too little can destroy synapses. Surprisingly, we aren’t sure exactly how this happens. Usually, glutamate is cleared from synapses by support cells called astrocytes, but neurons also have this ability. Using a mouse model of Alzheimer’s disease, we have evidence that glutamate cleanup by neurons is faulty even before cognitive symptoms appear. We propose that this impairment may be key to the early failure in synaptic communication and the eventual breakdown of synapses.

This project will dive deeper into this idea by supplying neurons with critical molecules that will help improve glutamate clearance. We predict that this early intervention will delay or prevent future synaptic loss, cognitive impairment, and disease.

Translational

Translational

Krista Power, University of Ottawa

Co-funded with Brain Canada Foundation

Title: Targeting the microbiota-gut-brain axis with diet and exercise interventions in individuals with subjective cognitive decline.

Award/Grant: Proof of Concept Grant

People who have or are at high risk of Alzheimer’s disease have changes in the bacteria community within their digestive system. These bacterial changes can increase inflammation in the body and brain, which may increase dementia risk. Lifestyle behaviours, such as healthy eating and physical activity, are associated with reduced dementia risk and can help maintain a healthy bacterial community. Our project will examine whether a brain-healthy eating program and/or a physical activity program improves cognitive function and whether changes in bacteria in the digestive system are responsible for these changes. We will enroll people who have noticed changes in their thinking (subjective cognitive decline) but do not yet have cognitive impairment or dementia.

Treatment

Treatment

Jolene Phelps, University of Victoria

Title: Optimization of extracellular vesicle-based treatments in a 3D bioprinted model of Alzheimer’s disease.

Award/Grant: Postdoctoral Award

Stem cell therapies hold promise for the treatment of Alzheimer's disease and related dementias. More recently, scientists have discovered that stem cells act through molecules (i.e., proteins, lipids, RNAs) they release. More specifically, these molecules can be released within tiny nanoparticles (extracellular vesicles, EVs), which protect and transport the molecules where they need to go. EVs can be produced and used in therapies in place of cells, and are advantageous because they are non-living, which makes them safer and more translatable. This project aims to test stem cell-derived EVs in a 3D bio-printed model of Alzheimer's disease to determine if and what type of EVs can produce functional benefits. Further study hopes to determine what molecular components within the EVs may be responsible. This work will help us to better understand how EVs interact with brain cells, and will enable us to develop more targeted, precise treatments in the future.

Dawn Bowdish, McMaster University

Co-funded with Brain Canada Foundation 

Title: Assessing the Efficacy of a Hypomethylating Agent to Decrease Post-Pneumonia Cognitive Impairments.

Award/Grant: Proof of Concept Grant

Serious respiratory infections like pneumonia can cause people to develop dementia much faster than they normally would. Preventing infections would give older adults more years of brain health and independence. Vaccines help but don’t always work so we need treatments to slow dementia in people who become seriously ill. We want to understand what happens in the brain after an infection to figure out how to stop dementia and to test a drug in mice to see if we can prevent dementia after infections.

Iva Zovkic, University of Toronto

Co-funded with Brain Canada Foundation

Title: Evaluating the histone variant macroH2A1.1 as a master regulator of PARP1-Sirt1 balance in Alzheimer’s disease.

Award/Grant: Proof of Concept Grant

Alzheimer’s disease (AD) is characterized by dysregulated function of many proteins, which makes it difficult to identify a single therapeutic target. This is further complicated because many proteins that become dysfunctional in AD serve critical functions in the healthy brain, so inhibiting their activity completely can produce undesirable side-effects. Two such proteins are PARP1 and SIRT1, which promote normal function in the healthy brain, but become dysregulated in AD. These proteins compete for the same cellular resources, so excessively high levels of PARP1 in AD result in impaired function of SIRT1, thus contributing to neurodegeneration and memory decline. In this project, we will test the hypothesis that a protein called histone macroH2A1.1 regulates the balance between PARP1 and SIRT1 and that restoring normal mH2A1.1 function will preserve activity of all three proteins to prevent neurodegeneration and memory decline.

Taufik Valiante, UHN/ CAMH/ University of Toronto

Co-funded with Brain Canada Foundation 

Title: DBS-PPN-AD: A Pilot Clinical Trial Investigating Deep Brain Stimulation of the Pedunculopontine Nucleus for the Treatment of Alzheimer's Disease

Award/Grant: Proof of Concept Grant

Gamma oscillations (GO) are electrical signals detected in the brain that are essential for memory and cognition. GO are products of the activity of types of brain cells called parvalbumin interneurons (PVIN) and are both impaired in Alzheimer’s disease (AD). Remarkably, stimulation of PVIN has restored GO and rescued memory in AD preclinical studies. Moreover, PVIN stimulation has attenuated abnormal proteins accumulation that are central to AD pathophysiology. Deep brain stimulation (DBS) is a common neurosurgical procedure where an implanted electrode is used to stimulate a specific area in the brain. The pedunculopontine nucleus (PPN) is an area in the brainstem recognized as being the main driver of GO in the brain. Therefore, we are undertaking a pilot clinical trial where we aim to provide proof of concept for the ability of DBS to augment PVIN activity (restore GO), address amyloid beta accumulation, and rescue memory in AD patients.

Olivier Parent, Douglas Research Center, Douglas Mental Health University Institute

Co-funded with FRQ

Title: Using advanced MRI sequences to assess the severity of vascular lesions in the brain.

Award/Grant: Doctoral Award

White matter hyperintensities (WMH) are a type of brain abnormality detectable with magnetic resonance imaging (MRI). They are among the most widely detected radiological abnormalities in the elderly population and are indicative of vascular dysfunction. WMHs increase the risk of multiple types of dementia but particularly Alzheimer’s Disease. Crucially, WMHs can be indicative of different types of tissue alterations, likely influencing the potential reversibility of the lesions through cardiovascular risk factor management. In my project, I will use advanced MRI sequences to estimate pathophysiological processes underlying WMHs (e.g., oedema, inflammation, demyelination). Using those estimates, I will characterize if WMHs in different spatial locations have different pathophysiological processes. Finally, using machine learning techniques, I will use this acquired knowledge to investigate which spatial and pathophysiological pattern of WMHs, combined with which specific lifestyle and pharmacological interventions targeting cardiovascular risk factors, are predictive of a reduction in WMHs and better clinical outcomes.

Simon Wing, McGill University Health Centre Research Institute

Co-funded with Brain Canada Foundation

Title: Targeting the USP19 deubiquitinating enzyme for the treatment of Alzheimer’s disease.

Award/Grant: Proof of Concept Grant

Alzheimer’s disease progresses due to the spreading of aggregates of tau protein and amyloid protein from unaffected to affected regions of the brain. We do not understand how these aggregates spread and how to prevent the spreading. We recently discovered that taking out the USP19 gene in mice with Alzheimer’s-like disease slows the spread of aggregates, results in less inflammation in the brain, less brain atrophy and longer survival. Our study will determine whether giving a chemical (a possible drug) that inhibits the action of the USP19 protein to mice with Alzheimer’s like disease will have the same effect as the loss of the USP19 gene in the mice. We will also ask whether this potential drug acts by decreasing inflammation in the brain. Positive results in these studies will lead to further development of this chemical into a drug for testing in patients.