Identification of genetic and lifestyle risk factors of unhealthy brain ageing to direct mechanistic studies using post-mortem brain tissue
Principal Investigator: Dr Greg Sutherland
Approved Research ID: 49777
Approval date: September 30th 2019
The major diseases of unhealthy brain ageing, dementia and stroke, are two of the top four causes of death in Australia. Dementia is now the leading cause of mortality in females and 2nd in males. The latter is due to the ageing population and the absence of disease modifying therapies. The most common form of dementia is Alzheimer's disease (AD) with many considering that drugs reducing the build-up of peptides called beta-amyloid are the most likely cure. Yet to date drugs that have reduced beta-amyloid in clinical trials have not slowed cognitive decline suggesting that adjunctive or alternative approaches will be required. The symptoms of dementia result from the irreversible loss of brain cells so any cure needs to be used before symptoms occur. Lifestyle factors such as alcohol and smoking, inactivity and sedentary behaviour, and their direct biomedical consequences such as hypertension and obesity are known to increase the risk of dementia along with 30 known genetic variants and their probable interactions. In Australia, persons over 55 years are the most likely age group to consume alcohol at harmful levels and to smoke the highest number of cigarettes. We intend to mine massive UK Biobank database to confirm known and find unknown genetic and lifestyle risk factors and interactions between them. To look for early disease clues we will compare non-demented individuals who are grouping by their performance on different thinking tasks, the appearance of their brain on imaging and whether they have a first degree relatives has AD/dementia. We intend to then find out how these risk factors affect the brain by selecting similar groups from our bank of over 300 well-characterised, largely non-demented brain donors (Sutherland, Sheedy et al. 2014) . The overall goal is to identify early mechanisms of cognitive decline, that precede the symptoms of dementia.