30 May 2023
HEIDI DOUGLASS | h.douglass@unsw.edu.au
The breadth of research groups and studies at CHeBA make it a leader in the global epidemiology of dementia, with the data available making the Centre a rich resource for not just researchers, but also students.
According to the Co-Directors of CHeBA, Professor Perminder Sachdev and Professor Henry Brodaty, the calibre of students the Centre has supported has been outstanding.
Recent PhD graduate, Dr Rebecca Koncz, is no exception. Dr Koncz led a world first study using data from CHeBA’s long-standing Older Australian Twins Study, using a brain imaging technique called amyloid PET.
β-amyloid plaque build-up is a hallmark feature of Alzheimer’s disease, which is the leading cause of dementia worldwide. Dr Koncz’s thesis aimed to determine: 1) what proportion of amyloid burden is attributable to genes, and what proportion is determined by environmental, or modifiable, risk factors; 2) whether the presence of cerebral small vessel disease or vascular risk factors such as high blood pressure, high cholesterol or diabetes influence the build-up of β-amyloid; and 3) the role of genetics in the relationship between β-amyloid, cerebral small vessel disease and cognitive function.
Dr Koncz, who is a passionate advocate for healthy brain ageing and dementia prevention strategies being accessible to everyone, found that that the heritability of amyloid is moderate – which means that genes play a moderate role (40-50%) in determining the difference in brain amyloid load between twins.
Her second study, using participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), showed that cerebral small vessel disease did not directly impact on the build-up of β-amyloid over time. Fasting blood glucose was the only vascular risk factor that influenced amyloid build-up.
Looking at the genetic basis of amyloid, cerebral small vessel disease and cognition in the OATS cohort, the third study found a genetic relationship only between markers of small vessel disease and processing speed (how fast the brain processes information), but no genetic relationship between amyloid and cognitive function.
Clearly, Dr Koncz’s research has addressed important questions given we know that the build-up of amyloid – one of the key pathologies in Alzheimer’s disease - occurs decades prior to the onset of symptoms such as memory impairment.
One of the central PhD chapters on the heritability of amyloid had broad-reaching impact as a world-first study of identical and non-identical twins. With the study determining that genes play a moderate role in amyloid build up, there is an opportunity to really address environmental factors. Ultimately, if we can identify what these modifiable risk factors are, we may be able to limit or slow down the accumulation of amyloid and influence the development of Alzheimer’s disease.
Dr Rebecca Koncz
According to Dr Koncz, fortnightly supervision with Professor Perminder Sachdev was a vital component of her PhD.
Apart from guiding the content and direction of the thesis, the incisive feedback I received during my supervision sessions provided a guiding light throughout the PhD and beyond to shape my career
Dr Rebecca Koncz
Dr Koncz felt that Professor Sachdev struck an important balance between giving her autonomy but also providing guidance where needed. Her secondary supervisors were generous in providing their expertise in neuroimaging and statistics and were also prompt and helpful when questions arose.
Looking to the future, Dr Koncz hopes to be a positive example for the next generation of clinician scientists.
She also hopes that research can go on to find what the environmental determinants of amyloid are and reduce or slow that accumulation – ultimately reducing the chance of people developing Alzheimer’s disease.
