TDRA Studies

Principal Investigators: Sandra Black, Krista Lanctôt, Mary Pat McAndrews

Above average electrical activity in a part of the brain known as the hippocampus can be unhealthy. This hyperactivity is common in other diseases such as epilepsy, but for some individuals with a family history of Alzheimer’s disease it may contribute to the progression of the disease. This study will recruit healthy participants with specific genetics and a family history of disease to look at how common hyperactivity is in this population, and whether low doses of an approved medication for epilepsy (Levetiracetam) can reduce it.

This study is under development.

Principal Investigators: Jean Chen, Linda Mah

Higher heart rate variability (HRV) is associated with greater emotional well-being and cognitive function. Study investigators have demonstrated that increasing the duration of exhalation-to -inhalation breathing ratio leads to increased HRV in healthy older and young adults. Autonomic dysfunction is well-established in major depressive disorder (MDD) and Alzheimer’s disease (AD), and emerging data shows evidence of the same in mild cognitive impairment (MCI). The goal of this study is to assess autonomic function through measurement of HRV in remitted MDD (rMDD), amnestic MCI (aMCI), rMDD with comorbid aMCI (rMDD+aMCI), and cognitively unimpaired (CU) older adults at rest and in response to a physiological challenge. Results from this study will contribute to our knowledge of the association between autonomic dysfunction and AD risk, and could identify potential autonomic targets for AD prevention.

This study was awarded seed funding in the 2021 Temerty-Tanz-TDRA Seed Fund competition. Learn more. 

Participate in this study.

Principal Investigator: Sandra Black 

Site Principal Investigators: Howard Chertkow, Corinne Fischer, Sanjeev Kumar, Carmela Tartaglia  

The Brain-Eye Amyloid Memory (BEAM) study is investigating whether measurements of the eye can be used with other tests to detect dementia earlier. By comparing the results of non-invasive tests similar to those done in an eye doctor’s office with established tests of cognition, magnetic resonance imaging (MRI) and a positron emission tomography (PET) scan, researchers can look for links between changes in parts of the eye in dementia. PET scans can detect amyloid that has deposited in the brain, which is a hallmark of Alzheimer’s disease. 

More information on the BEAM Study

Participate in this study.

Principal Investigator: Anna Gagliardi PhD

The AIM of this study is to generate insight on how to design and implement culturally-safe strategies that promote dementia risk reduction among immigrant women.

The OBJECTIVES are to:

1. Screen the 264 studies (2000-2016) included in a prior review of strategies used for health promotion to immigrants for those targeting immigrant women
2. Update that prior review to identify studies published from 2017 to current targeting immigrant women
3. Based on compiled studies, describe the design, cultural tailoring, implementation and impact of strategies used to promote dementia risk reduction to immigrant women, and
4. Develop and disseminate knowledge mobilization outputs to organizations that can promote or implement the strategies.

Investigators: Amer Burhan, Mary Chiu, Ron Beleno, Kristina Kokorelias, Tarek Rajji, Irene Rubinstein (Knowledge User), Joel Sadavoy, Adriana Schnall, Michael Smith, Jeanie Zabukovec, Lynn Zhu

This project will adapt an existing program for caregivers/care partners of people living with dementia into the virtual reality (VR) space.

The CARERS program is an eight-week, closed-group psychotherapy program for caregivers/care partners of people living with dementia. It involves problem-solving therapy, emotional support, and skills-building through simulated scenarios. The program is highly effective; however, it is time and resource intensive, and is not widely accessible – especially for remote communities. Adapting this program into a VR environment will help to overcome these barriers.

The VR simulation training environment will be co-designed with caregivers/care partners of people living with dementia, along with other typical demographic representatives. The VR tool will then be evaluated for feasibility, acceptability, and tolerability before pilot testing is conducted. Pilot testing will assess if the program is ready for community implementation through evaluating its clinical efficacy in improving quality of relationship with people living with dementia, resilience, competence, and reducing caregiver/care partner depression and stress.

Principal Investigator: Yona Lunsky

The overall aim of this study is to evaluate the implementation and effectiveness of an IDD dementia screening program in Canada.

Specific objectives include:

1. To understand implementation of the IDD dementia screening program within community disability agencies across Canada (addressed by study components 1 and 2).

2. To understand implementation of the IDD dementia screening program from the perspective of family caregivers across Canada (addressed by study components 1 and 3)

This study is under development.

This study, led by Dr. Osnat Melamed, and funded by the Canadian Institute of Health Research (CIHR)’s Brain Health and Cognitive Impairment in Aging (BHCIA) Research Initiative, aims to provide a comprehensive review of women-specific smoking cessation approaches that address sex and gender-related barriers to quitting, with a particular focus on women with Diabetes Mellitus.

The specific objectives of this research are:

1. Perform a systematic review of existing literature to identify smoking treatment programs specifically designed for women, and summarize the strategies employed by these programs to address sex and gender related obstacles in smoking cessation.

2. Facilitate consultation workshops involving our principal knowledge user, Diabetes Action Canada (DAC), patient partners and stakeholders to discuss the review findings and establish a sex and gender informed approach to support women with DM in quitting smoking.

3. Foster the dissemination of new knowledge and stakeholder insights through the co-creation of knowledge mobilization (KM) products, including written materials, a podcast, and an animation video.

Principal Investigator: Carmela Tartaglia

Collaborators: Daniel Felsky, Morris Freedman, Ekaterina Rogaeva, David Tang-Wai,

In order to optimize treatment and support strategies for neurodegenerative diseases (e.g., Alzheimer’s disease), timely and accurate diagnosis is critical. So too is the availability of prognostic information, which provides a scientific prediction of the likely development of a disease and its outcomes.

There remains considerable uncertainty in diagnosing neurodegenerative diseases. Studies comparing clinical diagnoses with autopsy diagnoses reveal that, even at specialized dementia clinics, about 30% of people with a clinical diagnosis of Alzheimer’s disease (AD) are misdiagnosed. The accuracy of clinical diagnosis is even lower for other dementias, including Frontotemporal dementia, Lewy body disease and vascular dementia. This study aims to better diagnose neurodegenerative diseases and ultimately enable targeted treatment in people living with specific underlying disease pathologies. This will be accomplished through the development of non-invasive diagnostic and prognostic algorithms - based on biomarkers and supported by AI - in older individuals presenting with cognitive complaints.

A biomarker is an objective medical sign (i.e., something happening within a cell or organism in the body) used to measure the presence or progress of disease. Through a series of standardized assessments, including the Toronto Cognitive Assessment (TorCA), researchers will be testing for the presence of key biomarkers in a group of 500 people living with cognitive impairments. Collecting the same information on a population of people with different types of cognitive impairment will reveal important clues about what makes them different. Information from the various assessments will be used to create a score that includes all the biomarkers examined, and how they relate to a person’s cognitive impairment (i.e., which neurodegenerative disease they have). Researchers will then assess if a patients biomarker profile can predict the progression of their cognitive symptoms over a one-year follow-up period.

Principal Investigators: Tarek Rajji, Graham Collingridge, Evelyn Lambe, Sanjeev Sockalingam

In persons aged 65 and above, depression ranks as one of the strongest modifiable risk factors for developing dementia. As such, optimizing the treatment of depression is a viable research pathway for dementia prevention. 

The INSPiRE-D study combines bench (i.e., laboratory science) and bedside research, and involves adjusting an existing form of brain stimulation therapy to make it more potent for the treatment of depression. Transcranial magnetic stimulation (TMS) is a noninvasive form of brain stimulation therapy; it uses magnetic pulses to stimulate nerve cells in the brain, which can improve symptoms of depression. Theta-burst stimulation (TBS) is a newer form of TMS where the magnetic pulses are applied in a certain pattern, called bursts. Using an animal model of depression (i.e., mice in a lab), the INSPiRE-D study will investigate whether changing the rhythm or spacing of TBS pulses to the brain could deliver long-lasting brain plasticity. Once optimized in the animal model, the TBS will be adapted for adults with acute depression using clinical brain stimulation.

Throughout the project, people with lived experience and trainees will be directly involved in order to integrate knowledge translation about bench-to-bedside research throughout all phases of the study.

This study is under development. Learn more.

Investigators: Amer Burhan, Peter Derkach, Anuroop Duggal, Corinne Fischer, Morris Freedman, Sean Hill, Andrea Iaboni, Sanjeev Kumar, Krista Lanctôt, Clement Ma, Frank Palmer, Gillian Strudwick 

Many residents of long-term care homes (LTCHs) live with dementia and associated behavioral problems such as agitation. An even larger proportion of LTCH residents have cognitive impairment but not dementia, or other mental health illnesses that put them at increased risk of developing dementia. The LTCH Research Database aims to improve the treatment of cognitive and behavioural problems in residents of LTCHs.

There are several potential reasons for less than optimal treatment and variability in care of cognitive and behavioural problems in persons living in LCTHs, including:

• Lack of standardized assessment and triage
• Lack of consistent evidence-based treatment approach
• Lack of measurement-based care (i.e., care based on objective assessments)

The creation of the LTCH Research Database will standardize existing care for residents of LTCHs living with cognitive and behavioural problems. This will be accomplished by developing a platform of structured assessment (at intake and otherwise), followed by implementation of structured interventions guided by measurement-based care using an interdisciplinary approach. The database will also allow research into biomarkers and novel treatment interventions for residents and their caregivers in terms of feasibility, efficacy, and effect on the utilization of health system resources.

Investigators: Sandra Black, Bradley Buchsbaum, Howard Chertkow, Daniel Felsky, Morris Freedman, Sean Hill, Sanjeev Kumar, Ekaterina Rogaeva, Stephen Strother, David Tang-Wai, Carmela Tartaglia

Clinical Operations Manager: Aymin Mumtaz 
Software Engineer: Nima Nourhaghighi

The Memory Clinics Research Database is TDRA’s foundational project; it uses a standardized test of cognition developed by TDRA scientists, and captures a variety of clinical data from consenting patients.

Cognitive tests and clinical data are used by neurologists to help support a diagnosis, but these data are also very interesting and useful to researchers. Collecting the same information on a population of people living with different types of dementia reveals important clues about what makes them different. Having this detailed description will also help researchers make more informed decisions about which trials would be a good fit, and to better track outcomes.

This project is now an operation of a TDRA Research Working Group (RWG), which is focusing on data quality and completeness, and making data from the over 2000 participants available for research. So far, two projects that use this data have been funded, including:

1. Artificial Intelligence in the Memory Clinic: This project will develop artificial intelligence-based approaches to support the diagnosis of dementia. 
2. Improving Prognostic Confidence in Neurodegenerative Diseases Causing Dementia Using Peripheral Biomarkers and Integrative Modelling: This project will develop non-invasive diagnostic and prognostic algorithms in older individuals presenting with cognitive complaints, to ultimately enable targeted treatment in patients with specific underlying disease pathologies.

More information on the Memory Clinics Research Database (previously called Dementia Clinical Research Database)

Find a publication by Mattan Soffer et al, utlizing the memory clinic database.

Principal Investigators: Corinne Fischer, Neda Rashidi-Ranjbar, Tom Schweizer

This study investigates the efficacy of photobiomodulation (PBM), a form of therapy that uses lights, in the treatment of early Alzheimer’s disease (AD).

Mitochondria are found in most cells in the human body. They generate chemical energy which powers a cell’s biochemical reactions, and this energy is stored in a molecule called adenosine triphosphate (ATP). A potential AD-causing mechanism is the dysfunction of mitochondria in the brain; however, an effective therapy that targets mitochondrial dysfunction is still missing. PMB is a noninvasive technique for enhancing mitochondrial function via reducing oxidative stress and increasing ATP levels. It delivers infrared light to the brain, and can be safely administered to awake outpatients. PMB is a promising novel therapy for early AD; however, the effectiveness and mechanism of action of PBM in AD remains to be studied. This is what this study will explore.

Principal Investigator: Yona Lunsky

The aim of this study is to co-design, implement and evaluate a national, virtual brain health education program ‘Brain Health-IDD’ for:

• aging individuals, ages 40 and older, who identify as having an intellectual or developmental disability (IDD), as well as
• their family caregivers, and
• the health and social service providers who support them.

For each of the three participant groups, adults with IDD, family caregivers, and health and social service providers, this study will:

1) Evaluate the extent of participation and satisfaction with Brain Health-IDD;

2) Evaluate changes in knowledge and self-efficacy regarding brain health including identification and management of health-related aging concerns following participation in Brain Health-IDD.

For adults with IDD and family caregivers, the study will:

3) Evaluate changes in health behaviours related to social connections, sleep hygiene, and physical activity following participation in Brain Health-IDD and whether cognitive screening is initiated;

4) Evaluate changes in physical health, mental wellbeing and resilience following participation in Brain Health-IDD.

For health and social service providers, this study will:

5) Evaluate changes made to promote brain health among adults with IDD who they support following participation in Brain Health-IDD, including whether cognitive screening is initiated.

More to come on this study

Principal Investigators: Clement Hamani, Lorraine Kalia, Suneil Kalia, Philip Kim

Parkinson’s disease results from the death of brain cells which are necessary for many of our daily functions, including movement. Loss of movement control (i.e., motor symptoms) is a defining feature of Parkinson’s disease. However, people living with Parkinson’s disease also suffer from depression and dementia that can lead to memory problems (i.e., non-motor symptoms). Depression often occurs before motor symptoms, while dementia affects about 80% of people just 10 years after being diagnosed with Parkinson’s disease. Treatment for these non-motor symptoms could drastically improve the quality of lives of people affected by Parkinson’s disease.

Many people living with Parkinson’s disease have an abnormal accumulation of a normally occurring protein in the brain, called alpha-synuclein. The proteins clump together to form Lewy Bodies, which can cause brain cells to die. This project will examine the relationship between alpha-synuclein accumulation, brain cell death, depression, and memory problems in an animal model in which features of Parkinson’s disease are caused by rotenone, a pesticide associated with increased risk of Parkinson’s disease in humans. A recently discovered peptide, called PDpep1.3, has been shown to reduce alpha-synuclein accumulation in the brain, and is associated with decreases in brain cell death and motor symptoms. This project will test whether PDpep1.3 can also reduce depression and memory problems in the rotenone model of Parkinson’s disease. Results from this project will begin to define the potential interactions between depression and dementia in Parkinson’s disease.

This study was awarded seed funding in the 2022 Temerty-Tanz-TDRA Seed Fund competition. Learn more. 

Principal Investigators: Abhishek Datta, Kullervo Hynynen, Tarek K. Rajji

The treatments available for Alzheimer’s disease dementia (AD) have limited efficacy, likely because by the time AD manifests, it is too late to intervene. As such, finding interventions for patients who are at risk of developing AD could prevent progression to AD.

Mild Cognitive Impairment (MCI) is a clinical state that is considered a pre-stage to AD. In MCI, a part of the brain called the ‘prefrontal cortex’ supports compensatory mechanisms that could delay progression to AD. For example, executive functions, which are high-level cognitive skills used to control and coordinate other cognitive abilities and behaviours. Working memory is a key executive function, and a neurophysiologic process called ‘theta-gamma coupling’ (TGC) has been shown to index working memory.

This study examines the feasibility and preliminary effects of combining two non-invasive stimulation methods to engage TGC, and in turn, enhance working memory in amnestic people living with MCI. These stimulation methods include Transcranial Alternating Current Stimulation (tACS) to engage the prefrontal cortex and Focused Ultrasound (FUS) to engage the hippocampus. The hippocampus is another structure that is important to working memory and people living with MCI; it is found deep in the brain, and it cannot be reached with precision with tACS. The combination of these two stimulation interventions is innovative and could optimize the prefrontal cortex-hippocampus network for better cognitive function in people living with MCI.

This study is under development. 

Principal Investigators: Mary Pat McAndrews & Jennifer Rabin

Alzheimer disease (AD) and depression are two of the most common health conditions in older adults. The two disorders are associated with an overlapping set of symptoms that include memory difficulties. As a result, it can be difficult to determine whether a person’s memory problems are due to the early stages of AD, depression, or both. Providing an accurate diagnosis, as early as possible, is important to ensure that people receive the most effective treatment and care.

This project will use machine learning techniques to create a method for accurately determining whether someone has AD, depression, both conditions, or neither condition. A machine learning model will be trained to use cognitive test data (e.g., memory, language, attention scores) and brain data derived from an MRI scan to accurately make these classifications. The cognitive test data and brain data will come from four large cohort studies of older adults. The analysis will then be replicated on a separate dataset to evaluate the generalizability of the algorithm. If successful, this study will provide an affordable diagnostic tool that clinicians can use to accurately diagnose people with AD, depression, or both conditions.

This study was awarded seed funding in the 2022 Temerty-Tanz-TDRA Seed Fund competition. Learn more.

Investigators: Malcolm Binns, Sandra Black, Morris Freedman, Sanjeev Kumar, Tarek Rajji, Shlomit Rotenberg, David Tang-Wai, Stephen Strother 

Funded by the Alzheimer Society Research program, this study explores whether virtual assessments of praxis are more informative than traditional questionnaires to assess impairments in activities of daily living. This study has begun recruitment.

Participate in this study.

Principal Investigators: Damien Gallagher, Ariel Graff-Guerrero

Activation of the inflammatory response is known to play a role in causing amyloid-beta to accumulate. Study investigators previously found that over one third of older adults living with depression have persistent inflammation. One cause for this may be breakdown of the gut barrier, which helps ensure that bacteria living in our gut remain separate from the rest of our body. Depression has been associated with breakdown of the gut barrier and increased immune response to lipopolysaccharide (LPS), which is a product released from the cell membrane of bacteria that live in our gut. This study aims to determine if LPS is a key driver of inflammation and increased accumulation of amyloid-beta protein in the brain, thereby precipitating depression and subsequent cognitive decline in a proportion of older adults with depression.

This study was awarded seed funding in the 2021 Temerty-Tanz-TDRA Seed Fund competition. Learn more. 

Principal Investigators: Benoit H. Mulsant, Tarek K. Rajji, Nathan Hermann, Bruce G. Pollock

Mild Cognitive Impairment (MCI) is considered to be an early stage of dementia, and is typically followed by a progressive decline in cognitive ability. Prevention of Alzheimer’s Dementia with Cognitive Remediation plus Transcranial Direct Current Stimulation in Mild Cognitive Impairment and Depression (PACt-MD) investigates the effectiveness of games designed to boost and preserve cognition and non-invasive brain stimulation on slowing down the progression of MCI to Alzheimer’s disease.

More information on the PACt-MD Study

Principal Investigators: Sandra Black, Krista Lanctôt

Shrinkage or atrophy of the brain is a common effect of Alzheimer’s disease (AD), and is associated with a decline in cognitive ability. The SARTAN-AD study is comparing the effects of two approved medications for high blood pressure – Telmisartan and Perindopril – on their ability to stabilize the brain in people living with high blood pressure and AD.  Participants will be enrolled in this study for 12 months, and will have magnetic resonance imaging (MRI) and cognitive testing to measure whether there is any effect of the medication.

More information on the SARTAN-AD study

Principal Investigators: Angela Golas, Carmela Tartaglia

This study aims to better understand the interrelationship of depression, neurodegeneration, and cerebrovascular disease in patients with and without positive biomarkers for Alzheimer disease (AD). The investigators hypothesize that people living with depression will have larger white matter hyperintensities volume (associated with small vessel disease), and that this will relate to cognitive impairment in both AD and non-AD patients. The study will also compare the interrelationship between depression, cerebrovascular disease, and AD between males and females. The results could provide evidence for implicating cerebrovascular disease in depression and cognitive impairment in AD and non-AD patients. This could provide rationale for primary prevention of depression with control of vascular risk factors.

This study was awarded seed funding in the 2021 Temerty-Tanz-TDRA Seed Fund competition. Learn more.