Theme 1: Prevention

Focused on the underlying mechanisms and prevention of dementia

• Team 1: Clinical Genetics and Gene Discovery is led by Drs. Ekaterina Rogaeva and Ziv Gan-Or. This team includes 4 additional internationally-recognized Canadian experts in molecular/clinical genetics and functional genomic approaches (Drs. Peter St. George-Hyslop, Kathy Siminovitch, Guy Rouleau, and Ian Mackenzie). In Phase II, this team will continue to function as a platform, carrying out genotyping on CCNA research participants, as well as a research program that studies a range of neurodegenerative diseases that have similar symptoms. To increase the power of the dataset being built, the overall CCNA cohort will eventually be pooled with cohorts collected in the laboratories of each member of this team, and international consortia focused on discovering new disease genes or modifiers of clinical phenotypes. To highlight disease-associated variants/regions, we are planning to use Canadian core facilities and a shared platform of genomic informatics tools. This work will inform other CCNA translational teams and allow the construction of genetically-stratified cohorts that will be valuable for all CCNA teams and potential therapeutic trials. Team 1 will also underpin pre-clinical studies directed towards target discovery for novel therapeutics and diagnostics by identifying individuals with genotypes of interest for the creation of human neuronal cell models that will complement animal/cellular models.

• Team 2: Inflammation & Nerve Growth Factors is led by Drs. Margaret Fahnestock and Pedro Rosa-Neto, whose research team is working on the multidisciplinary aspects of brain repair and brain aging.

• Team 3: Protein Misfolding is led by Dr. Neil Cashman, who networks his lab (and two other CCNA labs) to investigate the fundamental and translational science on how misfolded proteins cause neurodegeneration in Alzheimer’s and Parkinson’s diseases.

• Team 4: Investigating Mechanisms of Alzheimer Disease to Develop New Therapies is led by Dr. Robert Bartha. The team’s goal is to identify the earliest metabolic, synaptic, and inflammatory changes in the brain that could provide new therapeutic targets and diagnostic biomarkers. The team uses cutting edge tools in its work, including novel animal models (to study specific aspects of disease) and automated cognitive testing in these models that is sensitive to small changes in the brain’s executive function and memory. Using some of the most advanced imaging equipment available in Canada, the team has developed non-invasive, high-resolution imaging methods that are sensitive to brain metabolism, function, and microstructure. These methods are designed to link the team’s results from the animal models to CCNA’s COMPASS-ND study. More broadly, the team is focused on understanding whether sex differences associated with metabolic and inflammatory changes can accelerate disease progression.

• Team 5: Diet and Prevention is led by Dr. Guylaine Ferland, whose studies aim to identify nutrition strategies that support optimal cognitive function with aging. Specifically, Ferland and her team study the relationships between lifelong dietary patterns, risk of cognitive decline with aging, and how diet-associated vascular and metabolic disorders affect this decline. This is, in part, achieved by conducting epidemiological studies that explore the inter-relationships amongst diet, physical activity, other lifestyle factors (e.g. social engagement, socioeconomic status), metabolic factors (e.g. inflammatory markers), and specific genes, using existing and emerging Canadian cohort studies. Through these analyses, the team aims to better characterize the individuals at high risk of cognitive decline and identify how diet, exercise, and lifestyle components interact. In parallel, Ferland’s team has launched a clinical trial (LEAD), exploring the effects of diet and exercise on the brain’s structure and its cognitive performance. The study includes older adults who have subjective cognitive decline (i.e. self-reported perception of memory or cognition problems) and vascular risk factors (obesity, T2DM, or hypertension). These groups have been targeted because they are at high risk for both Alzheimer’s disease and vascular dementias (and their combination), but are still performing cognitively within a normal range. With this trial, the team will determine whether the benefits of exercise training on brain outcome measures can be enhanced with dietary change, consistent with the Brain Health Food Guide (BHFG) that was recently developed by the team. To access both English and French versions of the guide, click here.