Genetics, Modifiable Risk Factors, Brain Health & Cognitive Function
This project aims to identify understudied and rare genetic variants that make substantial contribution to cognitive decline and dementia in the contexts of poor cardiometabolic and mental health.
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The global population is ageing rapidly, with major implications for population health. Cognitive decline across adulthood, which often precedes dementia, is a particular concern, as very limited or no options are currently available to slow or halt its progression.
Both genetic and environmental factors contribute to dementia. However, despite decades of research, only a fraction of the genetic variability and environmental risk underlying cognitive decline has been identified, and the biological mechanisms through which these exposures influence brain ageing remain largely unclear.
Rare genetic variants (with frequencies below 1%) have emerged as promising contributors because they may exert strong individual effects on disease risk. In parallel, poor cardiometabolic and mental health are well established modifiable risk factors for accelerated cognitive decline and neurodegeneration. Therefore, part of the unexplained cognitive variability may reflect interactions between rare genetic variants and major risk exposures.
This project investigates whether genetic variability in biological mechanisms essential for maintaining optimal cellular, tissue, and organ function, heightens vulnerability to neurocognitive decline and dementia when interacting with modifiable risk factors such as high blood pressure, elevated glucose and cholesterol levels, low physical activity, and poor mental health.
Ultimately, by applying a comprehensive, mechanism level analytical framework across multiple interconnected biological ageing mechanisms, and drawing on large established cohort data, this project will: (a) enhance novel gene discovery by assessing the impact of rare variants in ageing related pathways, in combination with modifiable risk factors, on cognitive decline and dementia; and (b) develop ageing mechanism based polygenic risk scores with direct relevance to prevention and precision medicine.
Research related to this project
- DNA repair genetic variability and cardiometabolic risk
- Antioxidant genetic variability and cardiometabolic risk
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Learn more about our research supported by the Dementia Research and Prevention Fund at ANU.
Members
Principal investigator
Professor
Co-Head DHEWS
Researcher
Senior Fellow
Co-Head DHEWS
Analytics and Biomolecular Research Officer
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